U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C31H24F3N5O3
Molecular Weight 571.5492
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of UMBRALISIB

SMILES

CC(C)OC1=C(F)C=C(C=C1)C2=NN([C@@H](C)C3=C(C4=CC=CC(F)=C4)C(=O)C5=CC(F)=CC=C5O3)C6=C2C(N)=NC=N6

InChI

InChIKey=IUVCFHHAEHNCFT-INIZCTEOSA-N
InChI=1S/C31H24F3N5O3/c1-15(2)41-24-9-7-18(12-22(24)34)27-26-30(35)36-14-37-31(26)39(38-27)16(3)29-25(17-5-4-6-19(32)11-17)28(40)21-13-20(33)8-10-23(21)42-29/h4-16H,1-3H3,(H2,35,36,37)/t16-/m0/s1

HIDE SMILES / InChI
Molecular Formula C31H24F3N5O3
Molecular Weight 571.5492
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Umbralisib (Ukoniq, TG Therapeutics) is an orally available PI3K delta inhibitor, targeting the delta isoform with nanomolar potency and several fold selectivity over the alpha, beta, and gamma isoforms of PI3K. The delta isoform of PI3K is strongly expressed in cells of hematopoietic origin and is believed to be important in the proliferation and survival of B-cell lymphocytes. On February 5, 2021, the Food and Drug Administration granted accelerated approval to umbralisib for the following indications: adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based regimen; adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy. However, on June 1, 2022, the FDA withdrew its approval for the cancer medicine Ukoniq due to safety concerns.

CNS Activity

Originator

Approval Year

2021
460
Targets

Targets

Primary TargetPharmacologyConditionPotency
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
9
Target ID: O00329
Gene ID: 5293.0
Gene Symbol: PIK3CD
Target Organism: Homo sapiens (Human)
Inhibitor
8504
 6.2 nM [Kd]
Casein kinase I isoform epsilon
2
Target ID: P49674
Gene ID: 102800317|||1454
Gene Symbol: CSNK1E
Target Organism: Homo sapiens (Human)
Inhibitor
8504
 180.0 nM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Withdrawn
Primary
Withdrawn
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1830 ng/mL
OTHER GOV'T
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=209
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
UMBRALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
750 ng/mL
OTHER GOV'T
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=209
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
UMBRALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
1680 ng/mL
OTHER GOV'T
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=209
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
UMBRALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
14200 ng × h/mL
OTHER GOV'T
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=209
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
UMBRALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
8830 ng × h/mL
OTHER GOV'T
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=209
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
UMBRALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
20700 ng × h/mL
OTHER GOV'T
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=209
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
UMBRALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
110 h
OTHER GOV'T
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=72
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
UMBRALISIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
91 h
OTHER GOV'T
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=72
800 mg single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
UMBRALISIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.2%
OTHER GOV'T
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=72
UMBRALISIB plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf#page=8
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf#page=8
Disc. AE: Diarrhea, Vomiting...
Other AEs: Death, Colitis...
AEs leading to
discontinuation/dose reduction:
Diarrhea (grade 3-4)
Vomiting (grade 3-4, <1%)
Upper respiratory tract infection (grade 3-4, <1%)
Transaminase increased (5%)
Neutropenia (5%)
Other AEs:
Death (grade 5, <1%)
Colitis
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf#page=8
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
Disc. AE: Death, Diarrhea...
Other AEs: Sepsis, Colitis...
AEs leading to
discontinuation/dose reduction:
Death (grade 5, 1.4%)
Diarrhea
Neutropenia (grade 3-4, 1.4%)
Rash (grade 3-4, 2.9%)
Transaminase elevation (4.3%)
Fatigue (1.4%)
Nausea (1.4%)
Upper respiratory tract infection (2.9%)
Vomiting (4.3%)
Musculoskeletal pain (1.4%)
Abdominal pain (2.9%)
Diarrhea (grade 3-4)
Pneumonia (grade 3-4, 2.8%)
Pneumonia (4.3%)
Colitis
Other AEs:
Sepsis (grade 3-4, 4.3%)
Colitis (grade 3-4)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
AEs

AEs

AESignificanceDosePopulation
Colitis
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf#page=8
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf#page=8
Neutropenia 5%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf#page=8
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf#page=8
Transaminase increased 5%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf#page=8
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf#page=8
Upper respiratory tract infection grade 3-4, <1%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf#page=8
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf#page=8
Vomiting grade 3-4, <1%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf#page=8
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf#page=8
Diarrhea grade 3-4
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf#page=8
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf#page=8
Death grade 5, <1%
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf#page=8
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/213176s000lbl.pdf#page=8
Fatigue 1.4%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
Musculoskeletal pain 1.4%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
Nausea 1.4%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
Abdominal pain 2.9%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
Upper respiratory tract infection 2.9%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
Pneumonia 4.3%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
Transaminase elevation 4.3%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
Vomiting 4.3%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
Colitis Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
Diarrhea Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
Colitis grade 3-4
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
Neutropenia grade 3-4, 1.4%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
Pneumonia grade 3-4, 2.8%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
Rash grade 3-4, 2.9%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
Sepsis grade 3-4, 4.3%
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
Diarrhea grade 3-4
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
Death grade 5, 1.4%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: FED
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/213176Orig1Orig2s000MultidisciplineR.pdf#page=122
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
2252
substrate
1193

inhibitor
2438
inhibitor
2507
inhibitor
2217

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1741

CYPs
29

CYP2C8
1057

CYP1A2
2153

CYP2B6
926

CYP2C19
2057
MATE1
182

OCT2
434

CYP3A
220

BCRP
697

MATE2-K
33

OAT3
391

CYP1A2
1197

P-gp
2052

OATP1B1
503

OATP1B3
435

OAT1
395
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYPs
35
no (co-administration study)
Comment: Not expected to significantly impact the PK of cytochrome (CYP) sensitive substrates.
Page: 59.0
CYP1A2
2333
 no
CYP2B6
1160
 no
CYP2D6
2546
 no
P-gp
1932
 no
no (co-administration study)
Comment: Not expected to significantly impact the PK of P-gp sensitive substrates.
Page: 59.0
P-gp
1932
 yes [IC50 0.0653 uM]
yes (co-administration study)
Comment: Increased fexofenadine absorption (42% higher Cmax), increased AUCt (9%) and AUCinf (10%)
Page: 73 | 76
CYP2C8
1117
 yes [IC50 10.6 uM]
CYP2C19
2141
 yes [IC50 13.5 uM]
CYP2C9
2497
 yes [IC50 3.4 uM]
CYP3A4
2633
 yes [IC50 3.9 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
BCRP
697
 no
MATE1
182
 no
MATE2-K
33
 no
OAT1
395
 no
OAT3
391
 no
OATP1B1
503
 no
OATP1B3
435
 no
OCT2
434
 no
P-gp
2052
 no
CYP1A2
1197
 weak
CYP2C9
1193
 yes
CYP3A
220
 yes
no (co-administration study)
Comment: Strong CYP3A inhibitors is not expected to significantly impact the PK of umbralisib.
Page: 59 | 73 | 76
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
2263
PubMed

PubMed

TitleDatePubMed
Umbralisib: Treatment for a Rare Lymphoma?
2019-06
Can umbralisib bring PI3Kδ out of the shadows?
2018-04
Umbralisib Inhibits PI3Kδ with Less Toxicity Than Previous Inhibitors.
2018-04

Sample Use Guides

In Vivo Use Guide
Relapsed or refractory marginal zone lymphoma or relapsed or refractory follicular lymphoma: recommended dosage: 800 mg orally once daily with food
Route of Administration: Oral
In Vitro Use Guide
Umbralisib (TGR-1202), a novel, next generation PI3Kδ inhibitor, inhibits PI3Kδ activity in enzyme and cell based assays with IC50 and EC50 values of 22.2 & 24.3 nM, respectively.
Substance Class Chemical
Created
by admin
on Mon Mar 31 22:41:13 GMT 2025
Edited
by admin
on Mon Mar 31 22:41:13 GMT 2025
Record UNII
38073MQB2A
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RP-5264
Preferred Name English
UMBRALISIB
USAN   INN  
Official Name English
4H-1-BENZOPYRAN-4-ONE, 2-((1S)-1-(4-AMINO-3-(3-FLUORO-4-(1-METHYLETHOXY)PHENYL)-1H-PYRAZOLO(3,4-D)PYRIMIDIN-1-YL)ETHYL)-6-FLUORO-3-(3-FLUOROPHENYL)-
Systematic Name English
Umbralisib [WHO-DD]
Common Name English
2-((1S)-1-(4-AMINO-3-(3-FLUORO-4-(1-METHYLETHOXY)PHENYL)-1H-PYRAZOLO(3,4-D)PYRIMIDIN-1-YL)ETHYL)-6-FLUORO-3-(3-FLUOROPHENYL)-4H-1-BENZOPYRAN-4-ONE
Systematic Name English
TGR-1202
Code English
UMBRALISIB [USAN]
Common Name English
umbralisib [INN]
Common Name English
RP5264
Code English
TGR-1202 FREE BASE
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 687519
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
FDA ORPHAN DRUG 680019
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
FDA ORPHAN DRUG 533016
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
NCI_THESAURUS C129825
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
FDA ORPHAN DRUG 687419
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
FDA ORPHAN DRUG 554216
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
NCI_THESAURUS C2152
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
FDA ORPHAN DRUG 726819
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
FDA ORPHAN DRUG 552216
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
Code System Code Type Description
DRUG BANK
DB14989
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
PRIMARY
USAN
CD-144
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
PRIMARY
EPA CompTox
DTXSID601337137
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
PRIMARY
NCI_THESAURUS
C104413
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
PRIMARY
WIKIPEDIA
Umbralisib
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
PRIMARY
CAS
1532533-67-7
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
PRIMARY
SMS_ID
100000175025
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
PRIMARY
PUBCHEM
72950888
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
PRIMARY
DAILYMED
38073MQB2A
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
PRIMARY
MANUFACTURER PRODUCT INFORMATION
TGR-1202 FREE BASE
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
PRIMARY MedKoo CAT NO: 205938, CAS NO.: 1532533-67-7(free base), 1532533-75-7(sulfate)Description: TGR-1202, also known as RP5264 , is a highly specific, orally available, PI3K delta inhibitor, targeting the delta isoform with nanomolar potency and several fold selectivity over the alpha, beta, and gamma isoforms of PI3K. Inhibition of PI3K delta signaling with TGR-1202 has demonstrated robust activity in numerous pre-clinical models and primary cells from patients with hematologic malignancies.(Last Updated: 9/24/2015)
FDA UNII
38073MQB2A
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
PRIMARY
INN
10350
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
PRIMARY
RXCUI
2478439
Created by admin on Mon Mar 31 22:41:13 GMT 2025 , Edited by admin on Mon Mar 31 22:41:13 GMT 2025
PRIMARY
Related Record Type Details
CYTOCHROME P450 1A2
METABOLIC ENZYME -> SUBSTRATE
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
The plasma protein binding is ?99.7% and was independent of concentration between 2 and 5 ?M.
CYTOCHROME P450 2C19
METABOLIC ENZYME -> INHIBITOR
CYTOCHROME P450 2C9
METABOLIC ENZYME -> SUBSTRATE
CYTOCHROME P450 2C9
METABOLIC ENZYME -> INHIBITOR
CYTOCHROME P450 2C8
METABOLIC ENZYME -> INHIBITOR
CYTOCHROME P450 3A4
METABOLIC ENZYME -> INHIBITOR
Structure of UMBRALISIB
EXCRETED UNCHANGED
following a single radiolabeled dose of umbralisib 800 mg to healthy subjects
FECAL
Structure of UMBRALISIB TOSYLATE
SALT/SOLVATE -> PARENT
Structure of UMBRALISIB
EXCRETED UNCHANGED
following a single radiolabeled dose of umbralisib 800 mg to healthy subjects
URINE
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT DELTA ISOFORM
TARGET -> INHIBITOR
IC50
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> INHIBITOR
Related Record Type Details
Structure of UMBRALISIB
ACTIVE MOIETY
Drugs: Carfilzomib(Primary), TGR 1202(Primary) Indication: Cancer Focus: Adverse reactions, Therapeutic Use Most Recent Event: 10 Dec 2015 New trial record
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC
Structure of UMBRALISIB
Volume of Distribution PHARMACOKINETIC
Structure of UMBRALISIB
Biological Half-life PHARMACOKINETIC
Structure of UMBRALISIB
blood-to-plasma ratio PHARMACOKINETIC
Structure of UMBRALISIB
NIH
NCATS
PRIVACY NOTICE
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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