Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR5975)
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 Progeria [ICD11: LD2B] Approved [1]
Myelodysplastic syndrome [ICD11: ICD11: 2A37] Phase 3 [2]
Hepatitis D virus infection [ICD11: ICD11: 1E50-1E51] Phase 2 [3]
Lung cancer [ICD11: ICD11: 2C25] Discontinued in Phase 3 [4]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 638.8 Topological Polar Surface Area 79.5
Heavy Atom Count 36 Rotatable Bond Count 3
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 3
Cross-matching ID
PubChem CID
148195
ChEBI ID
CHEBI:47097
CAS Number
193275-84-2
TTD Drug ID
D0W4HZ
Formula
C27H31Br2ClN4O2
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
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
Lonafarnib metabolite M1 DM005094 N. A. Oxidation - Oxidationn 1 [5] , [6]
Lonafarnib metabolite M2 DM005095 N. A. Other reaction - Dehydration 2 [5] , [6]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR005524 Lonafarnib Lonafarnib metabolite M1 Oxidation - Oxidationn CYP3A4 ... [5], [6]
MR005525 Lonafarnib metabolite M1 Lonafarnib metabolite M2 Other reaction - Dehydration CYP3A4 ... [5], [6]
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[5] , [6]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[5]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[5]
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 Identification of human liver cytochrome P450 enzymes responsible for the metabolism of lonafarnib (Sarasar). Drug Metab Dispos. 2006 Apr;34(4):628-35.
6 Identification of unstable metabolites of Lonafarnib using liquid chromatography-quadrupole time-of-flight mass spectrometry, stable isotope incorporation and ion source temperature alteration

If you find any error in data or bug in web service, please kindly report it to Dr. Yin and Dr. Li.