PONESIMOD

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H25ClN2O4S
Molecular Weight	460.974
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	2
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC\N=C1/S\C(=C/C2=CC(Cl)=C(OC[C@H](O)CO)C=C2)C(=O)N1C3=CC=CC=C3C

InChI

InChIKey=LPAUOXUZGSBGDU-STDDISTJSA-N

InChI=1S/C23H25ClN2O4S/c1-3-10-25-23-26(19-7-5-4-6-15(19)2)22(29)21(31-23)12-16-8-9-20(18(24)11-16)30-14-17(28)13-27/h4-9,11-12,17,27-28H,3,10,13-14H2,1-2H3/b21-12-,25-23-/t17-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C23H25ClN2O4S
Molecular Weight	460.974
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	2
Optical Activity	UNSPECIFIED

Description
Sources: https://pubmed.ncbi.nlm.nih.gov/33939119|https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213498s000lbl.pdf

Ponesimod is an experimental drug for the treatment of multiple sclerosis (MS) graft-versus-host disease and psoriasis. It acts on certain types of white blood cells (lymphocytes) which are involved in the autoimmune attack on myelin seen in multiple sclerosis (MS). Ponesimod is an orally active, reversible, and selective sphingosine-1-phosphate receptor (S1PR1) modulator. The drug is in phase II clinical trial for the treatment of graft-versus-host disease. In addition, the phase III clinical trial comparing ponesimod to teriflunomide in relapsing-remitting MS is ongoing.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sphingosine 1-phosphate receptor Edg-1 16 Target ID: CHEMBL4333 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28489480 \| https://www.ncbi.nlm.nih.gov/pubmed/28812220	Modulator 846		5.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Multiple sclerosis 107 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213498s000lbl.pdf	Primary		Approved 8583	PONVORY Approved Use Indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Launch Date 2021

C_max

Value	Dose	Analyte	Population
48.55 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=38	5 mg single, intravenous dose: 5 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
61.4 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=38	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
37.1 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=43	5 mg single, intravenous dose: 5 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
48.5 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=43	5 mg single, intravenous dose: 5 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
61.4 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=43	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.4 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=77	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
13.7 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=77	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
27.2 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=77	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
71 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=77	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
163 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=77	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
274 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=77	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
20.3 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=82	5 mg 1 times / day multiple, oral dose: 5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
48.5 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=82	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
91.7 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=82	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
40.3 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=82	5 mg 1 times / day multiple, oral dose: 5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
88.3 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=82	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
207 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=82	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
46.8 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=83	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
138 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=83	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
292 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=83	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
411 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=83	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
54.7 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=93	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
51.4 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=93	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
49.2 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=93	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
48.2 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=93	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
46.8 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=97	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
54.5 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=97	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
50 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=97	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
194 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=102	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
196 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=102	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1246 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=38	5 mg single, intravenous dose: 5 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
2124 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=38	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
1028 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=43	5 mg single, intravenous dose: 5 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1335 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=43	5 mg single, intravenous dose: 5 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2236 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=43	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
96 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=77	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
405 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=77	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
913 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=77	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2344 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=77	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5266 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=77	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
9153 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=77	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
292 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=82	5 mg 1 times / day multiple, oral dose: 5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
684 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=82	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1318 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=82	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
643 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=82	5 mg 1 times / day multiple, oral dose: 5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1400 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=82	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3473 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=82	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
667 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=83	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2085 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=83	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4277 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=83	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6325 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=83	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2190 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=93	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3320 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=93	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5070 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=93	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1650 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=93	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1587 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=97	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1773 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=97	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1554 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=97	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
6719 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=102	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7627 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=102	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
27.6 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=43	5 mg single, intravenous dose: 5 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
32.9 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=43	5 mg single, intravenous dose: 5 mg route of administration: Intravenous experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
31.7 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=43	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
21.7 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=77	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
30.1 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=77	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
33.4 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=77	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
27.7 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=77	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
28.8 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=77	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
31.4 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=77	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
30.9 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=82	5 mg 1 times / day multiple, oral dose: 5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
32.1 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=82	10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
32.7 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=82	20 mg 1 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
33.5 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=83	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
45.7 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=93	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
55.6 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=93	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
80.5 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=93	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
31.6 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=93	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
34.4 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=97	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
27.9 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=97	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
26.4 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=97	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
28.9 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=102	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
33.1 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=102	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	PONESIMOD plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.42% OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=9 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=67			PONESIMOD plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 mg 1 times / day multiple, oral Highest studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000OtherR.pdf https://clinicaltrials.gov/ct2/show/NCT02029482	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000OtherR.pdf https://clinicaltrials.gov/ct2/show/NCT02029482	Other AEs: Lethargy, Sensory disturbance... Other AEs: Lethargy (1 pt) Sensory disturbance (8.3%) Somnolence (8.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000OtherR.pdf https://clinicaltrials.gov/ct2/show/NCT02029482
20 mg 1 times / day multiple, oral Recommended Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000OtherR.pdf#page=29	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000OtherR.pdf#page=29	Disc. AE: Dyspnea, ALT increased... Other AEs: Headache, Drug-induced liver injury... AEs leading to discontinuation/dose reduction: Dyspnea (7 patients) ALT increased (5 patients) Macular edema (5 patients) AST increased (3 patients) Pregnancy (3 patients) Hepatic enzyme increased (3, 3 patients) Pregnancy of partner (2 patients) Hypertension (2 patients) Lymphocyte count decreased (2 patients) Nausea (2 patients) Dyspnea (3 patients) Lymphocyte count decreased (2 patients) Lymphopenia (3, 2 patients) Other AEs: Headache (3, 6 patients) Drug-induced liver injury (3, 2 patients) Fatigue (3, 2 patients) Hysterectomy (3, 2 patients) Intervertebral disc protrusion (3, 2 patients) Pain in extremity (3, 2 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000OtherR.pdf#page=29
20 mg 1 times / day multiple, oral Recommended Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000OtherR.pdf#page=30	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000OtherR.pdf#page=30	Disc. AE: Macular edema, Dyspnea... Other AEs: Abdominal pain, Hepatocellular injury... AEs leading to discontinuation/dose reduction: Macular edema (4 patients) Dyspnea (3 patients) Unintended pregnancy (3 patients) Multiple sclerosis (2 patients) Angioedema (2 patients) Invasive ductal breast carcinoma (2 patients) Other AEs: Abdominal pain (2 patients) Hepatocellular injury (2 patients) Nausea (2 patients) Edema peripheral (2 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000OtherR.pdf#page=30
20 mg 1 times / day multiple, oral Recommended Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf	Disc. AE: Macular edema, ALT increased... Other AEs: Abdominal pain upper, Appendicitis... AEs leading to discontinuation/dose reduction: Macular edema (3, 2 patients) ALT increased (1 pt) Atrioventricular block second degree (1 pt) Bradycardia (3, 1 pt) Other AEs: Abdominal pain upper (3, 1 pt) Appendicitis (3, 1 pt) Chest pain (3, 1 pt) Dyspnea (3, 1 pt) Headache (3, 1 pt) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf
10 mg 1 times / day multiple, oral Studied dose Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000OtherR.pdf#page=30	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000OtherR.pdf#page=30	Disc. AE: Unintended pregnancy, Multiple sclerosis... AEs leading to discontinuation/dose reduction: Unintended pregnancy (1 pt) Multiple sclerosis (1 pt) Angioedema (1 pt) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000OtherR.pdf#page=30
10 mg 1 times / day multiple, oral Studied dose Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf	Disc. AE: ALT increased, Atrioventricular block second degree... Other AEs: Headache... AEs leading to discontinuation/dose reduction: ALT increased (1 pt) Atrioventricular block second degree (2 patients) Dyspnea (1 pt) Palpitations (1 pt) Other AEs: Headache (3, 1 pt) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf
40 mg 1 times / day multiple, oral Studied dose Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000OtherR.pdf#page=30	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000OtherR.pdf#page=30	Disc. AE: Macular edema, Dyspnea... AEs leading to discontinuation/dose reduction: Macular edema (1 pt) Dyspnea (2 patients) Multiple sclerosis (1 pt) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000OtherR.pdf#page=30
40 mg 1 times / day multiple, oral Studied dose Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf	Disc. AE: ALT increased, Bradycardia... Other AEs: Headache... AEs leading to discontinuation/dose reduction: ALT increased (1 pt) Bradycardia (1 pt) Dyspnea (4 patients) Dyspnea exertional (2 patients) Palpitations (1 pt) Other AEs: Headache (3, 2 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000MedR.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252 inducer 1087	inducer 440 inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT2B7 197 UGT1A1 246 Efflux/Uptake transporters 1 CYP2C8 1057 CYP2C19 2057 OATP1B3 961 CYP2J2 33 CYP2E1 1060 CYP1A2 2153 CYP2B6 926 OCT2 779 MATE1 415 CYP2A6 879 OATP1B1 1079 OCT1 620 MATE2-K 77 BCRP 910 P-gp 1741 OAT1 725 OAT3 747	UGT1A10 331 UGT2B17 237 UGT2B10 131 UGT1A8 323 UGT2B15 236 CYP3A5 446 UGT1A3 470 CYP2J2 71 OATP1B1 503 ALDH1A1 1 P-gp 2052 UGT1A1 479 CYP4F12 10 OATP1B3 435 UGT2B7 456 UGT1A4 399 BCRP 697 CYP4F3A 3 UGT2B4 278 UGT1A6 343 UGT1A7 249 UGT1A9 423	CYP2B6 669 CYP1A2 832

Drug as perpetrator

Target	Modality	Activity
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=54 Page: 54.0	no [IC50 >100 uM]
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	no [IC50 >100 uM]
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	no [IC50 >100 uM]
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	no [IC50 >100 uM]
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	no [IC50 >100 uM]
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	no [IC50 >30 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=54 Page: 4 \| 8 \| 54 \| 59	no [IC50 >50 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=54 Page: 4 \| 8 \| 54 \|59	no [IC50 >50 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=54 Page: 4 \| 8 \| 54	no [IC50 >50 uM]
UGT1A1 303	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=58 Page: 4 \| 8 \| 58	no [IC50 >50 uM]
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=61 Page: 4 \| 8 \| 61	no
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=8 Page: 4 \| 8	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=8 Page: 4 \| 8 \| 59	no
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=61 Page: 4 \| 8 \|61	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=8 Page: 4 \| 8 \| 61	no
Efflux/Uptake transporters 1	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=4 Page: 4 \| 8	no
MATE2-K 77	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	yes [IC50 1.4 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=54 Page: 4 \| 8 \| 54	yes [IC50 14 uM]
UGT2B7 210	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=58 Page: 4 \| 8 \| 58	yes [IC50 17 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=54 Page: 4 \| 8 \| 54	yes [IC50 19 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=54 Page: 4 \| 8 \| 54	yes [IC50 36 uM]
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	yes [IC50 43 uM]
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	yes [IC50 7.1 uM]
CYP2J2 36	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=60 Page: 60.0	yes [IC50 7.8 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=54 Page: 4 \| 8 \| 54 \| 59	yes [IC50 9.6 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	yes [IC50 <=20 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=63 Page: 63.0	yes [IC50 <=30 uM]

Drug as victim

Target	Modality	Activity
UGT1A3 470	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	minor
UGT1A4 399	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	minor
UGT2B4 278	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	minor
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=8 Page: 8.0	no
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=8 Page: 8.0	no
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=8 Page: 8.0	no
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=8 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=66 Page: 8 \| 66	no
UGT1A10 331	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
UGT1A6 343	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
UGT1A7 249	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
UGT1A8 323	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
UGT1A9 423	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
UGT2B10 131	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
UGT2B15 236	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
UGT2B17 237	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
ALDH1A1 1	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=4 \| https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=50 Page: 4 \| 50	yes
CYP2J2 71	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=4 Page: 4.0	yes
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=4 Page: 4.0	yes
CYP3A5 446	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=4 Page: 4.0	yes
CYP4F12 10	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=4 Page: 4.0	yes
CYP4F3A 3	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=4 Page: 4.0	yes
UGT1A1 479	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=4 Page: 4 \| 52	yes
UGT2B7 456	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000ClinPharmR.pdf#page=4 Page: 4 \| 52	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000PharmR.pdf#page=18 Page: 18.0
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213498Orig1s000PharmR.pdf#page=18 Page: 18.0		ACT-338375 1

PubMed

Title	Date	PubMed
Cardiodynamic Interactions between Two S1P1 Receptor Modulators in an Experimental Clinical Setting: Different Pharmacokinetic Properties as an Opportunity to Mitigate First-Dose Heart Rate Effects.	2019-07-01	31266149
Discovery of Soft-Drug Topical Tool Modulators of Sphingosine-1-phosphate Receptor 1 (S1PR1).	2019-03-14	30891137
Therapeutic Potential of Ponesimod Alone and in Combination with Dimethyl Fumarate in Experimental Models of Multiple Sclerosis.	2019-03-01	31214480
Oral Therapies for Multiple Sclerosis.	2019-01-02	29500302
Discovery of super soft-drug modulators of sphingosine-1-phosphate receptor 1.	2018-10-15	30143424
Oral small molecules for psoriasis.	2018-09	30215633
Modeling Tolerance Development for the Effect on Heart Rate of the Selective S1P1 Receptor Modulator Ponesimod.	2018-06	28913826
Ponesimod, a selective sphingosine 1-phosphate (S1P1) receptor modulator for autoimmune diseases: review of clinical pharmacokinetics and drug disposition.	2018-05	28489480
S1P1 Modulator-Induced G αi Signaling and β-Arrestin Recruitment Are Both Necessary to Induce Rapid and Efficient Reduction of Blood Lymphocyte Count In Vivo.	2018-02	29203519
Modeling clinical efficacy of the S1P receptor modulator ponesimod in psoriasis.	2018-02	29174115
Sphingosine 1-Phosphate Receptor Modulators for the Treatment of Multiple Sclerosis.	2017-10	28812220
[Psoriatic arthritis : Drugs of the (near) future].	2017-08	28681115
Clinical pharmacology, efficacy, and safety aspects of sphingosine-1-phosphate receptor modulators.	2016-08	27249325

Sample Use Guides

In Vivo Use Guide

The recommended maintenance dosage is 20 mg taken orally once daily.

Route of Administration: Oral

In Vitro Use Guide

Ponesimod had an EC50 of 5.7 nM for the human S1P1 receptor compared to an EC50 of 25.3 nM for the endogenous ligand S1P, but had considerably less potency against human S1P2 S1P3, S1P4 and S1P5 receptors (EC50s 59.1 to > 10,000 nM)

Substance Class	Chemical Created by `admin` on `Wed Apr 02 09:53:21 GMT 2025` Edited by `admin` on `Wed Apr 02 09:53:21 GMT 2025`
Record UNII	5G7AKV2MKP
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

ACT-128800

Preferred Name

English

PONESIMOD

Official Name

English

5-(3-CHLORO-4-(((2R)-2,3-DIHYDROXYPROPYL)OXY)BENZ-(Z)-YLIDENE)-2-((Z)-PROPYLIMINO)-3-(O-TOLYL)THIAZOLIDIN-4-ONE

Common Name

English

(2Z,5Z)-5-(3-CHLORO-4-((2R)-2,3-DIHYDROXYPROPOXY)BENZYLIDENE)-3-(2-METHYLPHENYL)-2-(PROPYLIMINO)-1,3-THIAZOLIDIN-4-ONE

Systematic Name

English

PONESIMOD [ORANGE BOOK]

Common Name

English

PONESIMOD [USAN]

Common Name

English

(2Z,5Z)-5-(3-CHLORO-4-((2R)-2,3-DIHYDROXYPROPOXY)PHENYLMETHYLIDENE)-3-(2-METHYLPHENYL)-2-(PROPYLIMINO)-1,3-THIAZOLIDIN-4-ONE

Systematic Name

English

ponesimod [INN]

Common Name

English

4-THIAZOLIDINONE, 5-((3-CHLORO-4-((2R)-2,3-DIHYDROXYPROPOXY)PHENYL)METHYLENE)-3-(2-METHYLPHENYL)-2-(PROPYLIMINO)-, (2Z,5Z)-

Systematic Name

English

PONVORY

Brand Name

English

Ponesimod [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C308