LONAFARNIB

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H31Br2ClN4O2
Molecular Weight	638.822
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC(=O)N1CCC(CC(=O)N2CCC(CC2)[C@H]3C4=C(CCC5=C3C(Br)=CC(Cl)=C5)C=C(Br)C=N4)CC1

InChI

InChIKey=DHMTURDWPRKSOA-RUZDIDTESA-N

InChI=1S/C27H31Br2ClN4O2/c28-20-12-19-2-1-18-13-21(30)14-22(29)24(18)25(26(19)32-15-20)17-5-9-33(10-6-17)23(35)11-16-3-7-34(8-4-16)27(31)36/h12-17,25H,1-11H2,(H2,31,36)/t25-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C27H31Br2ClN4O2
Molecular Weight	638.822
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://adisinsight.springer.com/drugs/800009901
Curator's Comment: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/22620979 http://www.eigerbio.com/hepatitis-d/about-lonafarnib/

Lonafarnib is a well-characterized, late-stage, orally active inhibitor of farnesyl transferase, an enzyme involved in modification of proteins through a process called prenylation. It is Investigated for use/treatment in Progeria, Cancer, Hepatitis D. Lonafarnib completely inhibits Rheb prenylation and phosphorylation of S6 ribosomal protein in cell culture, indicating a lack of alternative Rheb prenylation. Other groups have demonstrated that inhibition of protein synthesis via inactivation of eukaryotic elongation factor (eEF2) could be an alternate mechanism of lonafarnib induced growth inhibition that is independent of RAS/p70S6K eEF. Adverse effects included fatigue, diarrhea, dyspnea and neutropenia and respiratory insufficiency.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Protein farnesyltransferase 13 Target ID: CHEMBL2094108 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9822558	Inhibitor 8504		1.9 nM [IC50]
Geranylgeranyl transferase type I 7 Target ID: CHEMBL2095164 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9822558	Inhibitor 8504		50000.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Progeria 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22620979	Primary	Phase II 1147	Unknown Approved Use Unknown
Chronic hepatitis D 1 Sources: http://www.eigerbio.com/hepatitis-d/lonafarnib-clinical-studies/	Primary	Phase II 1147	Unknown Approved Use Unknown
Chronic myelogenous leukemia 21 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16342165	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
229 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=156	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
291 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=156	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
237 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=156	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
283 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=156	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
422.88 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=157	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
491.1 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=157	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
456.67 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=157	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
392 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=158	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
312 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=158	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
445 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=158	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
510 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=158	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
117 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=159	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
248 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=159	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB 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/2020/213969Orig1s000IntegratedR.pdf#page=159	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: LOW-FAT
248 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=159	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
323 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=160	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
154 ng/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=160	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
1777 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213969s000lbl.pdf#page=14	115 mg/m² 2 times / day steady-state, oral dose: 115 mg/m² route of administration: Oral experiment type: STEADY-STATE co-administered:		LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
2695 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213969s000lbl.pdf#page=14	150 mg/m² 2 times / day steady-state, oral dose: 150 mg/m² route of administration: Oral experiment type: STEADY-STATE co-administered:		LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
2505 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=156	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
3870 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=156	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
2638 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=156	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
3685 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=156	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
13186.3 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=157	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
15762.97 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=157	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
13048.67 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=157	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
13400 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=158	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
7390 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=158	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
17600 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=158	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
13700 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=158	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
1150 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=159	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
1560 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=159	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1240 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=159	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: LOW-FAT
1560 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=159	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2077 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=160	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1556 ng × h/mL OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=160	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT
12365 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213969s000lbl.pdf#page=14	115 mg/m² 2 times / day steady-state, oral dose: 115 mg/m² route of administration: Oral experiment type: STEADY-STATE co-administered:		LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
19539 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213969s000lbl.pdf#page=14	150 mg/m² 2 times / day steady-state, oral dose: 150 mg/m² route of administration: Oral experiment type: STEADY-STATE co-administered:		LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.93 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=156	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
4.77 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=156	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
4.01 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=156	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
4.66 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=156	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		LONAFARNIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FED
13.37 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=157	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
10.27 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=157	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
12.28 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=157	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
13.8 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=158	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
9.32 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=158	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
16.3 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=158	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
10.5 h OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=158	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: RITONAVIR	RITONAVIR	LONAFARNIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.3% OTHER GOV'T https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213969Orig1s000IntegratedR.pdf#page=153			LONAFARNIB plasma	Homo sapiens

Doses

Dose	Population	Adverse events
400 mg 2 times / day steady-state, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: steady-state Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11181683/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/11181683/	DLT: Neutropenia, Thrombocytopenia... Other AEs: Vomiting, Nausea... Dose limiting toxicities: Neutropenia (grade 4, 1 pt) Thrombocytopenia (grade 4, 1 pt) Vomiting (grade 4, 1 pt) Other AEs: Vomiting (grade 1, 2 patients) Nausea (grade 2, 3 patients) Anorexia (grade 3, 2 patients) Diarrhea (grade 3, 1 pt) Diarrhea (grade 2, 1 pt) Diarrhea (grade 1, 1 pt) Fatigue (grade 2, 1 pt) Fatigue (grade 3, 1 pt) Fatigue (grade 2, 1 pt) Fatigue (grade 1, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/11181683/
300 mg 2 times / day steady-state, oral Studied dose Dose: 300 mg, 2 times / day Route: oral Route: steady-state Dose: 300 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11181683/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/11181683/	DLT: Neutropenia... Other AEs: Thrombocytopenia, Thrombocytopenia... Dose limiting toxicities: Neutropenia (grade 4, 1 pt) Other AEs: Thrombocytopenia (grade 1, 1 pt) Thrombocytopenia (grade 2, 1 pt) Nausea (grade 1, 2 patients) Nausea (grade 2, 1 pt) Anorexia (grade 1, 1 pt) Anorexia (grade 2, 1 pt) Diarrhea (grade 1, 2 patients) Diarrhea (grade 2, 1 pt) Vomiting (grade 1, 2 patients) Fatigue (grade 1, 1 pt) Fatigue (grade 2, 1 pt) Fatigue (grade 3, 1 pt) Neurotoxicity (grade 3, 1 pt) Creatinine increased (grade 1, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/11181683/

AEs

PubMed

Title	Date	PubMed
Exploring three-dimensional quantitative structural activity relationship (3D-QSAR) analysis of SCH 66336 (Sarasar) analogues of farnesyltransferase inhibitors.	2008-01	17442459
Phase 1 study of lonafarnib (SCH 66336) and imatinib mesylate in patients with chronic myeloid leukemia who have failed prior single-agent therapy with imatinib.	2007-09-15	17623836
Farnesyltransferase inhibitors inhibit T-cell cytokine production at the posttranscriptional level.	2007-09-15	17545504
Farnesyl transferase inhibitor resistance probed by target mutagenesis.	2007-09-15	17536018
Phase I and pharmacokinetic study of the oral farnesyltransferase inhibitor lonafarnib administered twice daily to pediatric patients with advanced central nervous system tumors using a modified continuous reassessment method: a Pediatric Brain Tumor Consortium Study.	2007-07-20	17634493
Farnesyltransferase inihibitors in hematologic malignancies.	2007-07	17293017
The farnesyltransferase inhibitor lonafarnib induces CCAAT/enhancer-binding protein homologous protein-dependent expression of death receptor 5, leading to induction of apoptosis in human cancer cells.	2007-06-29	17493934
New agents for treatment of advanced transitional cell carcinoma.	2007-05	17018703
Farnesyl transferase inhibitors impair chromosomal maintenance in cell lines and human tumors by compromising CENP-E and CENP-F function.	2007-04	17431110
The farnesyl transferase inhibitor, tipifarnib, is a potent inhibitor of the MDR1 gene product, P-glycoprotein, and demonstrates significant cytotoxic synergism against human leukemia cell lines.	2007-04	17268526
Inhibitors of the mevalonate pathway as potential therapeutic agents in multiple myeloma.	2007-03	16996129
Phase I study of the farnesyltransferase inhibitor lonafarnib with weekly paclitaxel in patients with solid tumors.	2007-01-15	17255280
A generalized response surface model with varying relative potency for assessing drug interaction.	2006-12	17156272
Identification of unstable metabolites of Lonafarnib using liquid chromatography-quadrupole time-of-flight mass spectrometry, stable isotope incorporation and ion source temperature alteration.	2006-11	17051523
Combination therapy with aromatase inhibitors: the next era of breast cancer treatment?	2006-09-18	16926831
Gateways to clinical trials.	2006-08-09	16894408
Lonafarnib in cancer therapy.	2006-06	16732721
[Farnesyl transferase inhibitors--a novel agent for breast cancer].	2006-04	16613692
Identification of human liver cytochrome P450 enzymes responsible for the metabolism of lonafarnib (Sarasar).	2006-04	16443667
Gateways to clinical trials.	2006-03	16636723
Identification of insulin-like growth factor binding protein-3 as a farnesyl transferase inhibitor SCH66336-induced negative regulator of angiogenesis in head and neck squamous cell carcinoma.	2006-01-15	16428512
Pilot study of lonafarnib, a farnesyl transferase inhibitor, in patients with chronic myeloid leukemia in the chronic or accelerated phase that is resistant or refractory to imatinib therapy.	2006-01-15	16342165
Myelodysplasia: when to treat and how.	2006	16516126
The combination of the farnesyl transferase inhibitor lonafarnib and the proteasome inhibitor bortezomib induces synergistic apoptosis in human myeloma cells that is associated with down-regulation of p-AKT.	2005-12-15	16118318
Microtubule interactions with chemically diverse stabilizing agents: thermodynamics of binding to the paclitaxel site predicts cytotoxicity.	2005-12	16356844
Hypoxia-inducible factor 1alpha and antiangiogenic activity of farnesyltransferase inhibitor SCH66336 in human aerodigestive tract cancer.	2005-09-07	16145048
The farnesyl transferase inhibitor (FTI) SCH66336 (lonafarnib) inhibits Rheb farnesylation and mTOR signaling. Role in FTI enhancement of taxane and tamoxifen anti-tumor activity.	2005-09-02	16006564
[Molecular targeted therapy for malignant brain tumors].	2005-09	16201575
Development of farnesyl transferase inhibitors: a review.	2005-09	16177281
Phase II study of the farnesyltransferase inhibitor lonafarnib with paclitaxel in patients with taxane-refractory/resistant nonsmall cell lung carcinoma.	2005-08-01	16028213
Farnesyltransferase inhibitor SCH66336 induces rapid phosphorylation of eukaryotic translation elongation factor 2 in head and neck squamous cell carcinoma cells.	2005-07-01	15994961
Lonafarnib reduces the resistance of primitive quiescent CML cells to imatinib mesylate in vitro.	2005-07	15889158
The synergistic combination of the farnesyl transferase inhibitor lonafarnib and paclitaxel enhances tubulin acetylation and requires a functional tubulin deacetylase.	2005-05-01	15867388
Farnesyltransferase inhibitor SCH-66336 downregulates secretion of matrix proteinases and inhibits carcinoma cell migration.	2005-05-01	15609318
Multicentre EORTC study 16997: feasibility and phase II trial of farnesyl transferase inhibitor & gemcitabine combination in salvage treatment of advanced urothelial tract cancers.	2005-05	15911238
Farnesyltransferase inhibitors in myelodysplastic syndrome.	2005-05	15865870
Isoprenylation of intracellular proteins as a new target for the therapy of human neoplasms: preclinical and clinical implications.	2005-05	15857290
Gateways to clinical trials.	2005-03	15834466
[Farnesyltransferase inhibitors: preliminary results in acute myeloid leukemia].	2005-03	15820917
Hit to Lead Success Stories--IBC Conference: Effective chemistry strategies for reducing attrition rates and speeding lead compounds into the pipeline. 31 January-1 February 2005, San Diego, CA, USA.	2005-03	15772889
Hyperleukocytosis complicating lonafarnib treatment in patients with chronic myelomonocytic leukemia.	2005-02	15538404
Quantitative analysis of the farnesyl transferase inhibitor lonafarnib (Sarasartrade mark, SCH66336) in human plasma using high-performance liquid chromatography coupled with tandem mass spectrometry.	2005	15996016
Synthesis of 5-bromopyridyl-2-magnesium chloride and its application in the synthesis of functionalized pyridines.	2004-12-23	15606096
Farnesyltransferase inhibition: who are the Aktors?	2004-11	15640614
Clinical activity of farnesyl transferase inhibitors in hematologic malignancies: possible mechanisms of action.	2004-11	15512806
Effects of insulin-like growth factor binding protein-3 and farnesyltransferase inhibitor SCH66336 on Akt expression and apoptosis in non-small-cell lung cancer cells.	2004-10-20	15494604
Gateways to clinical trials.	2004-09	15538546
[Ras signaling pathway as a target for farnesyltransferase inhibitors--a new, promising prospects in the treatment for malignant disorders].	2004	15765763
New targets for therapy in breast cancer: farnesyltransferase inhibitors.	2004	15535857
A multinomial Phase II study of lonafarnib (SCH 66336) in patients with refractory urothelial cancer.	2003-12-29	15907712

Patents

Sample Use Guides

In Vivo Use Guide

150 mg/m2 by mouth twice daily

Route of Administration: Oral

In Vitro Use Guide

Several experiments with 1 µM SCH66336 resulted in an average 70% reduction in S6 phosphorylation.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:22:50 GMT 2025` Edited by `admin` on `Mon Mar 31 21:22:50 GMT 2025`
Record UNII	IOW153004F
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SARASAR

Preferred Name

English

LONAFARNIB

Official Name

English

SCH-66336

Code

English

SCH66336

Code

English

LONAFARNIB [MI]

Common Name

English

SCH 66336

Code

English

1-PIPERIDINECARBOXAMIDE, 4-(2-(4-((11R-3,10-DIBROMO-8-CHLORO-6,11-DIHYDRO-5H-BENZO(5,6)CYCLOHEPTA(1,2-B)PYRIDIN-11-YL)-1-PIPERIDINYL)-2-OXOETHYL)-

Common Name

English

LONAFARNIB [ORANGE BOOK]

Common Name

English

ZOKINVY

Brand Name

English

LONAFARNIB [USAN]

Common Name

English

(+)-4-(2-(4-(11R)-3,10-DIBROMO-8-CHLORO-6,11-DIHYDRO-5H-BENZO(5,6)CYCLOHEPTA(1,2-B)PYRIDIN-11-YL)-PIPERIDIN-1-YL))-2-OXOETHYL)-PIPERIDINE-1-CARBOXAMIDE

Common Name

English

Lonafarnib [WHO-DD]

Common Name

English

lonafarnib [INN]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

411713