Details of the Drug

General Information of Drug (ID: DMGM2Z6)

Drug Name

Lonafarnib

Synonyms

Sarasar; Lonafarnib [USAN]; Sch 66336; Sch66336; SCH-066336; Sch-66336; Lonafarnib (USAN/INN); (+)-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; (+)-4-(2-(4-(8-chloro-3,10-dibromo-6,11-dihydro-5H-benzo(5,6)cyclohepta(1,2-b)pyridin-11-yl)-1-piperidinyl)-2-oxoethyl)-1-piperidinecarboxamide; (+)-4[2-[4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo[5,6] cyclohepta[1,2-b]-pyridin-11(R)-yl-1-piperidinyl]-2-oxo-ethyl]-1-piperidinecarboxamide; 4-(2-(4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo(5,6)cyclohepta(1,2-b)pyridin-11-yl)-1-piperidinyl)-2-oxoethyl)-1-piperidinecarboxamide; 4-(2-(4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo-(5,6)-cyclohepta(1,2-b)-pyridin-11(R)-yl)-1-piperidinyl)-2-oxo-ethyl)-1-piperidinecarboxamide; 4-{2-[4-(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

Indication

Disease Entry	ICD 11	Status	REF
Hutchinson-Gilford progeria syndrome	LD2B	Approved	[1]
Myelodysplastic syndrome	2A37	Phase 3	[2]
Hepatitis D virus infection	1E51.2	Phase 2	[3]
Non-small-cell lung cancer	2C25.Y	Discontinued in Phase 3	[4], [5]

Therapeutic Class

Anticancer Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

638.8

Topological Polar Surface Area (xlogp)

4.8

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 9869 +/- 6327 mcgh/L [6]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 1777 +/- 1083 mcg/L [6]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 2 h [6]
Elimination: Up to 240 hours following oral administration of 104 mg [14C]-lonafarnib in fasted healthy subjects, approximately 62% and <1% of the initial radiolabeled dose was recovered in feces and urine, respectively [6]
Half-life: The concentration or amount of drug in body reduced by one-half in 4 - 6 hours [6]
Metabolism: The drug is metabolized via the CYP3A4/5 and partially by CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, and CYP2E1 [7]
Vd: The volume of distribution (Vd) of drug is 97.4 L [6]

Chemical Identifiers

Formula: C27H31Br2ClN4O2
IUPAC Name: 4-[2-[4-[(2R)-6,15-dibromo-13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl]piperidin-1-yl]-2-oxoethyl]piperidine-1-carboxamide
Canonical SMILES: C1CN(CCC1CC(=O)N2CCC(CC2)[C@@H]3C4=C(CCC5=C3N=CC(=C5)Br)C=C(C=C4Br)Cl)C(=O)N
InChI: 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
InChIKey: DHMTURDWPRKSOA-RUZDIDTESA-N

Cross-matching ID

PubChem CID: 148195
ChEBI ID: CHEBI:47097
CAS Number: 193275-84-2
DrugBank ID: DB06448
TTD ID: D0W4HZ
INTEDE ID: DR1861
ACDINA ID: D01220

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Farnesyl protein transferase (Ftase)	TTXQKM3	FNTA_HUMAN; FNTB_HUMAN	Modulator	[1]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[8]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[8]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Hutchinson-Gilford progeria syndrome

ICD Disease Classification

LD2B

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Farnesyl protein transferase (Ftase)	DTT	FNTB; FNTA	5.43E-01	-0.1	-0.4
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	3.78E-02	4.07E-01	1.09E+00
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	3.90E-02	-3.45E-01	-1.49E+00

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Lonafarnib (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Metreleptin	DM1NOEK	Moderate	Increased metabolism of Lonafarnib caused by Metreleptin mediated induction of CYP450 enzyme.	Acute diabete complication [5A2Y]	[36]
Ivosidenib	DM8S6T7	Major	Decreased metabolism of Lonafarnib caused by Ivosidenib mediated inhibition of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[37]
Midostaurin	DMI6E0R	Major	Decreased metabolism of Lonafarnib caused by Midostaurin mediated inhibition of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[38]
Arn-509	DMT81LZ	Major	Increased metabolism of Lonafarnib caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[36]
Gilteritinib	DMWQ4MZ	Major	Decreased metabolism of Lonafarnib caused by Gilteritinib mediated inhibition of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[39]
Oliceridine	DM6MDCF	Major	Decreased metabolism of Lonafarnib caused by Oliceridine mediated inhibition of CYP450 enzyme.	Acute pain [MG31]	[40]
Ivabradine	DM0L594	Major	Decreased metabolism of Lonafarnib caused by Ivabradine mediated inhibition of CYP450 enzyme.	Angina pectoris [BA40]	[41]
Bedaquiline	DM3906J	Moderate	Decreased metabolism of Lonafarnib caused by Bedaquiline mediated inhibition of CYP450 enzyme.	Antimicrobial drug resistance [MG50-MG52]	[42]
ABT-492	DMJFD2I	Moderate	Decreased clearance of Lonafarnib due to the transporter inhibition by ABT-492.	Bacterial infection [1A00-1C4Z]	[36]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Lonafarnib caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[36]
Pexidartinib	DMS2J0Z	Major	Increased metabolism of Lonafarnib caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[43]
HKI-272	DM6QOVN	Major	Decreased metabolism of Lonafarnib caused by HKI-272 mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[44]
LY2835219	DM93VBZ	Major	Decreased metabolism of Lonafarnib caused by LY2835219 mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[45]
Tucatinib	DMBESUA	Major	Decreased metabolism of Lonafarnib caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[36]
Palbociclib	DMD7L94	Major	Decreased metabolism of Lonafarnib caused by Palbociclib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[46]
Cabazitaxel	DMPAZHC	Moderate	Decreased metabolism of Lonafarnib caused by Cabazitaxel mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[41]
Bosutinib	DMTI8YE	Major	Decreased metabolism of Lonafarnib caused by Bosutinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[41]
Macitentan	DMP79A1	Major	Decreased metabolism of Lonafarnib caused by Macitentan mediated inhibition of CYP450 enzyme.	Cardiovascular disease [BA00-BE2Z]	[47]
PF-04449913	DMSB068	Major	Decreased metabolism of Lonafarnib caused by PF-04449913 mediated inhibition of CYP450 enzyme.	Chronic myelomonocytic leukaemia [2A40]	[48]
Vilanterol	DMF5EK1	Moderate	Decreased metabolism of Lonafarnib caused by Vilanterol mediated inhibition of CYP450 enzyme.	Chronic obstructive pulmonary disease [CA22]	[49]
Levomilnacipran	DMV26S8	Major	Decreased metabolism of Lonafarnib caused by Levomilnacipran mediated inhibition of CYP450 enzyme.	Chronic pain [MG30]	[50]
Regorafenib	DMHSY1I	Moderate	Decreased metabolism of Lonafarnib caused by Regorafenib mediated inhibition of CYP450 enzyme.	Colorectal cancer [2B91]	[41]
Levonorgestrel	DM1DP7T	Moderate	Decreased metabolism of Lonafarnib caused by Levonorgestrel mediated inhibition of CYP450 enzyme.	Contraceptive management [QA21]	[36]
Ulipristal	DMBNI20	Moderate	Decreased metabolism of Lonafarnib caused by Ulipristal mediated inhibition of CYP450 enzyme.	Contraceptive management [QA21]	[36]
Pasireotide	DMHM7JS	Major	Decreased metabolism of Lonafarnib caused by Pasireotide mediated inhibition of CYP450 enzyme.	Cushing syndrome [5A70]	[36]
Osilodrostat	DMIJC9X	Major	Decreased metabolism of Lonafarnib caused by Osilodrostat mediated inhibition of CYP450 enzyme.	Cushing syndrome [5A70]	[51]
Ivacaftor	DMZC1HS	Major	Decreased metabolism of Lonafarnib caused by Ivacaftor mediated inhibition of CYP450 enzyme.	Cystic fibrosis [CA25]	[41]
MK-8228	DMOB58Q	Major	Decreased metabolism of Lonafarnib caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[36]
Vilazodone	DM4LECQ	Major	Decreased metabolism of Lonafarnib caused by Vilazodone mediated inhibition of CYP450 enzyme.	Depression [6A70-6A7Z]	[52]
OPC-34712	DMHG57U	Major	Decreased metabolism of Lonafarnib caused by OPC-34712 mediated inhibition of CYP450 enzyme.	Depression [6A70-6A7Z]	[53]
Empagliflozin	DMRF9YK	Moderate	Decreased clearance of Lonafarnib due to the transporter inhibition by Empagliflozin.	Diabetes mellitus [5A10]	[36]
Polatuzumab vedotin	DMF6Y0L	Major	Decreased metabolism of Lonafarnib caused by Polatuzumab vedotin mediated inhibition of CYP450 enzyme.	Diffuse large B-cell lymphoma [2A81]	[54]
Ingrezza	DMVPLNC	Major	Decreased metabolism of Lonafarnib caused by Ingrezza mediated inhibition of CYP450 enzyme.	Dystonic disorder [8A02]	[55]
Eslicarbazepine	DMZREFQ	Major	Increased metabolism of Lonafarnib caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[36]
Cannabidiol	DM0659E	Minor	Decreased metabolism of Lonafarnib caused by Cannabidiol mediated inhibition of CYP450 enzyme.	Epileptic encephalopathy [8A62]	[56]
Bay 80-6946	DMLOS5R	Major	Decreased clearance of Lonafarnib due to the transporter inhibition by Bay 80-6946.	Follicular lymphoma [2A80]	[57]
Tazemetostat	DMWP1BH	Major	Decreased metabolism of Lonafarnib caused by Tazemetostat mediated inhibition of CYP450 enzyme.	Follicular lymphoma [2A80]	[58]
Mirabegron	DMS1GYT	Minor	Decreased metabolism of Lonafarnib caused by Mirabegron mediated inhibition of CYP450 enzyme.	Functional bladder disorder [GC50]	[59]
Ripretinib	DM958QB	Major	Decreased metabolism of Lonafarnib caused by Ripretinib mediated inhibition of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[41]
Avapritinib	DMK2GZX	Major	Decreased metabolism of Lonafarnib caused by Avapritinib mediated inhibition of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[56]
Boceprevir	DMBSHMF	Major	Decreased metabolism of Lonafarnib caused by Boceprevir mediated inhibition of CYP450 enzyme.	Hepatitis virus infection [1E50-1E51]	[36]
Daclatasvir	DMSFK9V	Major	Decreased metabolism of Lonafarnib caused by Daclatasvir mediated inhibition of CYP450 enzyme.	Hepatitis virus infection [1E50-1E51]	[56]
Brentuximab vedotin	DMWLC57	Moderate	Decreased metabolism of Lonafarnib caused by Brentuximab vedotin mediated inhibition of CYP450 enzyme.	Hodgkin lymphoma [2B30]	[56]
MK-1439	DM215WE	Minor	Decreased metabolism of Lonafarnib caused by MK-1439 mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[60]
Cobicistat	DM6L4H2	Major	Decreased metabolism of Lonafarnib caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[36]
Rilpivirine	DMJ0QOW	Moderate	Decreased metabolism of Lonafarnib caused by Rilpivirine mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[41]
BMS-201038	DMQTAGO	Major	Decreased metabolism of Lonafarnib caused by BMS-201038 mediated inhibition of CYP450 enzyme.	Hyper-lipoproteinaemia [5C80]	[41]
Aliskiren	DM1BV7W	Moderate	Decreased clearance of Lonafarnib due to the transporter inhibition by Aliskiren.	Hypertension [BA00-BA04]	[61]
Lesinurad	DMUR64T	Moderate	Increased metabolism of Lonafarnib caused by Lesinurad mediated induction of CYP450 enzyme.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[36]
TP-434	DM5A31S	Minor	Decreased metabolism of Lonafarnib caused by TP-434 mediated inhibition of CYP450 enzyme.	Infectious gastroenteritis/colitis [1A40]	[62]
Suvorexant	DM0E6S3	Major	Decreased metabolism of Lonafarnib caused by Suvorexant mediated inhibition of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[41]
Tasimelteon	DMLOQ1V	Moderate	Decreased metabolism of Lonafarnib caused by Tasimelteon mediated inhibition of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[63]
Eluxadoline	DMYZ0P1	Moderate	Decreased metabolism of Lonafarnib caused by Eluxadoline mediated inhibition of CYP450 enzyme.	Irritable bowel syndrome [DD91]	[64]
Naloxegol	DML0B41	Major	Decreased metabolism of Lonafarnib caused by Naloxegol mediated inhibition of CYP450 enzyme.	Large intestine motility disorder [DB32]	[41]
Pemigatinib	DM819JF	Major	Decreased metabolism of Lonafarnib caused by Pemigatinib mediated inhibition of CYP450 enzyme.	Liver cancer [2C12]	[65]
Glycerol phenylbutyrate	DMDGRQO	Moderate	Increased metabolism of Lonafarnib caused by Glycerol phenylbutyrate mediated induction of CYP450 enzyme.	Liver disease [DB90-DB9Z]	[36]
Crizotinib	DM4F29C	Major	Decreased metabolism of Lonafarnib caused by Crizotinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[36]
Brigatinib	DM7W94S	Major	Decreased metabolism of Lonafarnib caused by Brigatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[66]
Ceritinib	DMB920Z	Major	Decreased metabolism of Lonafarnib caused by Ceritinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[36]
Lurbinectedin	DMEFRTZ	Major	Decreased metabolism of Lonafarnib caused by Lurbinectedin mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[67]
PF-06463922	DMKM7EW	Major	Increased metabolism of Lonafarnib caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[36]
Osimertinib	DMRJLAT	Major	Decreased metabolism of Lonafarnib caused by Osimertinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[68]
Pralsetinib	DMWU0I2	Major	Decreased metabolism of Lonafarnib caused by Pralsetinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[69]
Capmatinib	DMYCXKL	Major	Decreased metabolism of Lonafarnib caused by Capmatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[70]
Selpercatinib	DMZR15V	Major	Decreased metabolism of Lonafarnib caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[71]
Artemether	DM48QOT	Major	Decreased metabolism of Lonafarnib caused by Artemether mediated inhibition of CYP450 enzyme.	Malaria [1F40-1F45]	[41]
Artesunate	DMR27C8	Moderate	Decreased clearance of Lonafarnib due to the transporter inhibition by Artesunate.	Malaria [1F40-1F45]	[36]
Idelalisib	DM602WT	Major	Decreased metabolism of Lonafarnib caused by Idelalisib mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[36]
GDC-0199	DMH0QKA	Major	Decreased metabolism of Lonafarnib caused by GDC-0199 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[72]
IPI-145	DMWA24P	Major	Decreased metabolism of Lonafarnib caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[36]
Acalabrutinib	DM7GCVW	Major	Decreased metabolism of Lonafarnib caused by Acalabrutinib mediated inhibition of CYP450 enzyme.	Mature B-cell lymphoma [2A85]	[73]
Ibrutinib	DMHZCPO	Major	Decreased metabolism of Lonafarnib caused by Ibrutinib mediated inhibition of CYP450 enzyme.	Mature B-cell lymphoma [2A85]	[41]
Ponatinib	DMYGJQO	Major	Decreased metabolism of Lonafarnib caused by Ponatinib mediated inhibition of CYP450 enzyme.	Mature B-cell lymphoma [2A85]	[41]
Vemurafenib	DM62UG5	Moderate	Decreased metabolism of Lonafarnib caused by Vemurafenib mediated inhibition of CYP450 enzyme.	Melanoma [2C30]	[74]
Selumetinib	DMC7W6R	Major	Decreased metabolism of Lonafarnib caused by Selumetinib mediated inhibition of CYP450 enzyme.	Melanoma [2C30]	[75]
LGX818	DMNQXV8	Major	Decreased metabolism of Lonafarnib caused by LGX818 mediated inhibition of CYP450 enzyme.	Melanoma [2C30]	[76]
Dabrafenib	DMX6OE3	Major	Increased metabolism of Lonafarnib caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[36]
Ubrogepant	DM749I3	Major	Decreased metabolism of Lonafarnib caused by Ubrogepant mediated inhibition of CYP450 enzyme.	Migraine [8A80]	[77]
Rimegepant	DMHOAUG	Moderate	Decreased metabolism of Lonafarnib caused by Rimegepant mediated inhibition of CYP450 enzyme.	Migraine [8A80]	[78]
Panobinostat	DM58WKG	Major	Decreased metabolism of Lonafarnib caused by Panobinostat mediated inhibition of CYP450 enzyme.	Multiple myeloma [2A83]	[79]
Siponimod	DM2R86O	Major	Decreased metabolism of Lonafarnib caused by Siponimod mediated inhibition of CYP450 enzyme.	Multiple sclerosis [8A40]	[41]
Deflazacort	DMV0RNS	Major	Decreased metabolism of Lonafarnib caused by Deflazacort mediated inhibition of CYP450 enzyme.	Muscular dystrophy [8C70]	[56]
Fedratinib	DM4ZBK6	Major	Decreased metabolism of Lonafarnib caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[36]
Ruxolitinib	DM7Q98D	Major	Decreased metabolism of Lonafarnib caused by Ruxolitinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[80]
Vorapaxar	DMA16BR	Major	Decreased metabolism of Lonafarnib caused by Vorapaxar mediated inhibition of CYP450 enzyme.	Myocardial infarction [BA41-BA43]	[41]
Netupitant	DMEKAYI	Major	Decreased metabolism of Lonafarnib caused by Netupitant mediated inhibition of CYP450 enzyme.	Nausea/vomiting [MD90]	[36]
Entrectinib	DMMPTLH	Major	Decreased metabolism of Lonafarnib caused by Entrectinib mediated inhibition of CYP450 enzyme.	Non-small cell lung cancer [2C25]	[56]
S-297995	DM26IH8	Moderate	Decreased metabolism of Lonafarnib caused by S-297995 mediated inhibition of CYP450 enzyme.	Opioid use disorder [6C43]	[56]
Olaparib	DM8QB1D	Major	Decreased metabolism of Lonafarnib caused by Olaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[41]
Rucaparib	DM9PVX8	Major	Decreased metabolism of Lonafarnib caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[36]
MK-4827	DMLYGH4	Moderate	Decreased clearance of Lonafarnib due to the transporter inhibition by MK-4827.	Ovarian cancer [2C73]	[36]
Istradefylline	DM20VSK	Major	Decreased metabolism of Lonafarnib caused by Istradefylline mediated inhibition of CYP450 enzyme.	Parkinsonism [8A00]	[81]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Lonafarnib caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[82]
Lanreotide acetate	DMG6ZU4	Major	Decreased metabolism of Lonafarnib caused by Lanreotide acetate mediated inhibition of CYP450 enzyme.	Pituitary gland disorder [5A60-5A61]	[36]
Lefamulin	DME6G97	Major	Decreased metabolism of Lonafarnib caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[36]
Enzalutamide	DMGL19D	Major	Increased metabolism of Lonafarnib caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[36]
Relugolix	DMK7IWL	Moderate	Decreased clearance of Lonafarnib due to the transporter inhibition by Relugolix.	Prostate cancer [2C82]	[36]
Darolutamide	DMV7YFT	Moderate	Decreased metabolism of Lonafarnib caused by Darolutamide mediated inhibition of CYP450 enzyme.	Prostate cancer [2C82]	[83]
Selexipag	DMAHSU0	Moderate	Decreased clearance of Lonafarnib due to the transporter inhibition by Selexipag.	Pulmonary hypertension [BB01]	[36]
Riociguat	DMXBLMP	Moderate	Decreased metabolism of Lonafarnib caused by Riociguat mediated inhibition of CYP450 enzyme.	Pulmonary hypertension [BB01]	[41]
Axitinib	DMGVH6N	Major	Decreased metabolism of Lonafarnib caused by Axitinib mediated inhibition of CYP450 enzyme.	Renal cell carcinoma [2C90]	[41]
Upadacitinib	DM32B5U	Major	Decreased metabolism of Lonafarnib caused by Upadacitinib mediated inhibition of CYP450 enzyme.	Rheumatoid arthritis [FA20]	[84]
Tofacitinib	DMBS370	Major	Decreased metabolism of Lonafarnib caused by Tofacitinib mediated inhibition of CYP450 enzyme.	Rheumatoid arthritis [FA20]	[41]
Voxelotor	DMCS6M5	Major	Decreased metabolism of Lonafarnib caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[36]
LDE225	DMM9F25	Major	Decreased metabolism of Lonafarnib caused by LDE225 mediated inhibition of CYP450 enzyme.	Skin cancer [2C30-2C37]	[85]
Telotristat ethyl	DMDIYFZ	Major	Increased metabolism of Lonafarnib caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[43]
Larotrectinib	DM26CQR	Major	Decreased metabolism of Lonafarnib caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[41]
LEE011	DMMX75K	Major	Decreased metabolism of Lonafarnib caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[36]
Pitolisant	DM8RFNJ	Moderate	Increased metabolism of Lonafarnib caused by Pitolisant mediated induction of CYP450 enzyme.	Somnolence [MG42]	[36]
Pomalidomide	DMTGBAX	Moderate	Decreased metabolism of Lonafarnib caused by Pomalidomide mediated inhibition of CYP450 enzyme.	Systemic sclerosis [4A42]	[41]
Fostamatinib	DM6AUHV	Major	Decreased metabolism of Lonafarnib caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[86]
As-1670542	DMV05SW	Moderate	Decreased metabolism of Lonafarnib caused by As-1670542 mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[36]
Apixaban	DM89JLN	Major	Decreased metabolism of Lonafarnib caused by Apixaban mediated inhibition of CYP450 enzyme.	Thrombosis [DB61-GB90]	[41]
Brilinta	DMBR01X	Major	Decreased metabolism of Lonafarnib caused by Brilinta mediated inhibition of CYP450 enzyme.	Thrombosis [DB61-GB90]	[41]
Cabozantinib	DMIYDT4	Major	Decreased metabolism of Lonafarnib caused by Cabozantinib mediated inhibition of CYP450 enzyme.	Thyroid cancer [2D10]	[41]
Elagolix	DMB2C0E	Major	Increased metabolism of Lonafarnib caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[43]
Fluticasone	DMGCSVF	Major	Decreased metabolism of Lonafarnib caused by Fluticasone mediated inhibition of CYP450 enzyme.	Vasomotor/allergic rhinitis [CA08]	[87]
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⏷ Show the Full List of 117 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Isopropyl alcohol	E00070	3776	Antimicrobial preservative; Solvent
Ammonia	E00007	222	Alkalizing agent
Butyl alcohol	E00011	263	Flavoring agent; Solvent
Carmellose sodium	E00625	Not Available	Disintegrant
Ethanol	E00023	702	Antimicrobial preservative; Penetration agent; Solvent
Ferric oxide black	E00522	16211978	Colorant
Gelatin	E00630	Not Available	Other agent
Magnesium stearate	E00208	11177	lubricant
Poloxamer 188	E00645	Not Available	Emulsifying agent; Solubilizing agent; Surfactant
Potassium hydroxide	E00233	14797	Alkalizing agent
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Water	E00035	962	Solvent
Colcothar yellow	E00436	518696	Colorant
Haematite red	E00236	14833	Colorant
Shellac	E00695	Not Available	Coating agent; Film/membrane-forming agent; Microencapsulating agent; Modified-release agent
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⏷ Show the Full List of 18 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Lonafarnib 50 mg capsule	50 mg	Capsule	Oral
Lonafarnib 75 mg capsule	75 mg	Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
2	ClinicalTrials.gov (NCT00109538) Study of Lonafarnib Versus Placebo in Subjects With Either Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) (Study P02978AM3)(TERMINATED). U.S. National Institutes of Health.
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8024).
5	Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
6	FDA Approved Drug Products: Zokinvy (lonafarnib) capsules
7	Ostojic A, Vrhovac R, Verstovsek S: Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis. Future Oncol. 2011 Sep;7(9):1035-43. doi: 10.2217/fon.11.81.
8	Identification of human liver cytochrome P450 enzymes responsible for the metabolism of lonafarnib (Sarasar). Drug Metab Dispos. 2006 Apr;34(4):628-35.
9	Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
10	Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
11	Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
12	Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
13	Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
14	Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
15	Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
16	The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
17	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
18	Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95.
19	Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Biochem Biophys Res Commun. 1999 Jul 14;260(3):676-81.
20	Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72.
21	Drug Interactions Flockhart Table
22	Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8.
23	Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
24	Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
25	Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
26	Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.
27	Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia. Biologics. 2008 Sep;2(3):491-500.
28	Preclinical and clinical pharmacodynamic assessment of L-778,123, a dual inhibitor of farnesyl:protein transferase and geranylgeranyl:protein trans... Mol Cancer Ther. 2002 Jul;1(9):747-58.
29	Company report (Prescient)
30	Farnesyltransferase inhibitor BMS-214662 induces apoptosis in B-cell chronic lymphocytic leukemia cells. Leukemia. 2004 Oct;18(10):1599-604.
31	Ras farnesyltransferase: a new therapeutic target. J Med Chem. 1997 Sep 12;40(19):2971-90.
32	Aryl tetrahydropyridine inhibitors of farnesyltransferase: glycine, phenylalanine and histidine derivatives. Bioorg Med Chem Lett. 2003 Apr 7;13(7):1359-62.
33	A novel metal-chelating inhibitor of protein farnesyltransferase. Bioorg Med Chem Lett. 2003 May 5;13(9):1523-6.
34	Tricyclic farnesyl protein transferase inhibitors: crystallographic and calorimetric studies of structure-activity relationships. J Med Chem. 1999 Jun 17;42(12):2125-35.
35	Novel conformationally extended naphthalene-based inhibitors of farnesyltransferase. J Med Chem. 1997 Jun 6;40(12):1763-7.
36	Product Information. Zokinvy (lonafarnib). Eiger BioPharmaceuticals, Palo Alto, CA.
37	Product Information. Tibsovo (ivosidenib). Agios Pharmaceuticals, Cambridge, MA.
38	Dutreix C, Munarini F, Lorenzo S, Roesel J, Wang Y "Investigation into CYP3A4-mediated drug-drug interactions on midostaurin in healthy volunteers." Cancer Chemother Pharmacol 72 (2013): 1223-34. [PMID: 24085261]
39	Product Information. Xospata (gilteritinib). Astellas Pharma US, Inc, Deerfield, IL.
40	Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41. [PMID: 10721388]
41	Cerner Multum, Inc. "Australian Product Information.".
42	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
43	Patel S, Robinson R, Burk M "Hypertensive crisis associated with St. John's Wort." Am J Med 112 (2002): 507-8. [PMID: 11959071]
44	Abbas R, Hug BA, Leister C, Burns J, Sonnichsen D "Pharmacokinetics of oral neratinib during co-administration of ketoconazole in healthy subjects." Br J Clin Pharmacol 71 (2011): 522-7. [PMID: 21395644]
45	Product Information. Verzenio (abemaciclib). Lilly, Eli and Company, Indianapolis, IN.
46	Product Information. Ibrance (palbociclib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
47	Product Information. Opsumit (macitentan). Actelion Pharmaceuticals US Inc, South San Francisco, CA.
48	Product Information. Daurismo (glasdegib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
49	Product Information. Breo Ellipta (fluticasone-vilanterol). GlaxoSmithKline, Research Triangle Park, NC.
50	Product Information. Fetzima (levomilnacipran). Forest Pharmaceuticals, St. Louis, MO.
51	Product Information. Isturisa (osilodrostat). Recordati Rare Diseases Inc, Lebanon, NJ.
52	Product Information. Viibryd (vilazodone). Trovis Pharmaceuticals LLC, New Haven, CT.
53	Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc, Rockville, MD.
54	Product Information. Polivy (polatuzumab vedotin). Genentech, South San Francisco, CA.
55	Product Information. Ingrezza (valbenazine). Neurocrine Biosciences, Inc., San Diego, CA.
56	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
57	Product Information. Aliqopa (copanlisib). Bayer Pharmaceutical Inc, West Haven, CT.
58	Product Information. Tazverik (tazemetostat). Epizyme, Inc, Cambridge, MA.
59	Product Information. Myrbetriq (mirabegron). Astellas Pharma US, Inc, Deerfield, IL.
60	Product Information. Pifeltro (doravirine). Merck & Company Inc, Whitehouse Station, NJ.
61	Canadian Pharmacists Association.
62	Product Information. Xerava (eravacycline). Tetraphase Pharmaceuticals, Inc, Watertown, MA.
63	Product Information. Hetlioz (tasimelteon). Vanda Pharmaceuticals Inc, Rockville, MD.
64	Product Information. Viberzi (eluxadoline). Actavis Pharma, Inc., Parsippany, NJ.
65	Product Information. Pemazyre (pemigatinib). Incyte Corporation, Wilmington, DE.
66	Product Information. Alunbrig (brigatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
67	Product Information. Zepzelca (lurbinectedin). Jazz Pharmaceuticals, Palo Alto, CA.
68	Product Information. Tagrisso (osimertinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
69	Product Information. Gavreto (pralsetinib). Blueprint Medicines Corporation, Cambridge, MA.
70	Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
71	Product Information. Retevmo (selpercatinib). Lilly, Eli and Company, Indianapolis, IN.
72	Product Information. Venclexta (venetoclax). AbbVie US LLC, North Chicago, IL.
73	Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
74	Product Information. Zelboraf (vemurafenib). Genentech, South San Francisco, CA.
75	Product Information. Koselugo (selumetinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
76	Product Information. Braftovi (encorafenib). Array BioPharma Inc., Boulder, CO.
77	Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
78	Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
79	Hamberg P, Woo MM, Chen LC, et al. "Effect of ketoconazole-mediated CYP3A4 inhibition on clinical pharmacokinetics of panobinostat (LBH589), an orally active histone deacetylase inhibitor." Cancer Chemother Pharmacol 68 (2011): 805-13. [PMID: 21706316]
80	Product Information. Jakafi (ruxolitinib). Incyte Corporation, Wilmington, DE.
81	Product Information. Nourianz (istradefylline). Kyowa Kirin, Inc, Bedminster, NJ.
82	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
83	Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.
84	Product Information. Rinvoq (upadacitinib). AbbVie US LLC, North Chicago, IL.
85	Product Information. Odomzo (sonidegib). Novartis Pharmaceuticals, East Hanover, NJ.
86	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.
87	Arrington-Sanders R, Hutton N, Siberry GK "Ritonavir-fluticasone interaction causing Cushing syndrome in HIV-infected children and adolescents." Pediatr Infect Dis J 25 (2006): 1044-1048. [PMID: 17072128]