Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMGM2Z6)

Drug Name
Lonafarnib Drug Info
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]
Therapeutic Class
Anticancer Agents
Cross-matching ID
PubChem CID
148195
ChEBI ID
CHEBI:47097
CAS Number
CAS 193275-84-2
TTD Drug ID
DMGM2Z6
INTEDE Drug ID
DR1861
ACDINA Drug ID
D01220

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DME
DOT
Drug Status:
Clinical Trial Drug(s)
Discontinued Drug(s)
Approved Drug(s)
Investigative Drug(s)
Download the Complete Related Drug List
Drug(s) Targeting Farnesyl protein transferase (Ftase)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Zarnestra DMF30HL Acute myeloid leukaemia 2A60 Phase 3 [9]
L-778123 DMWSC5L Lymphoma 2A80-2A86 Phase 1 [10]
GGTI-2418 DM8U23L Solid tumour/cancer 2A00-2F9Z Phase 1 [11]
BMS214662 DM5M48F Non-small-cell lung cancer 2C25.Y Phase 1 [12]
L-745631 DM4UP7R Solid tumour/cancer 2A00-2F9Z Terminated [13]
ABT-839 DM4UN9A Non-small-cell lung cancer 2C25.Y Terminated [14]
MANUMYCIN A DM1SWOY N. A. N. A. Terminated [15]
SCH-44342 DMUL4VX N. A. N. A. Terminated [16]
RPR-113829 DMJ63GW N. A. N. A. Terminated [17]
RPR-114334 DMAIJT6 N. A. N. A. Terminated [17]
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Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [18]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [19]
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [20]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [21]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [22]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [23]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [24]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [25]
Prasterone DM67VKL Chronic obstructive pulmonary disease CA22 Approved [19]
Verapamil DMA7PEW Angina pectoris BA40 Approved [26]
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Drug(s) Metabolized By Cytochrome P450 3A5 (CYP3A5)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [27]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [28]
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [29]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [30]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [31]
Sulfasalazine DMICA9H Irritable bowel syndrome DD91.0 Approved [32]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [33]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [34]
Verapamil DMA7PEW Angina pectoris BA40 Approved [35]
Sorafenib DMS8IFC Adenocarcinoma 2D40 Approved [30]
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Drug(s) Affected By Prelamin-A/C (LMNA)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Selenium DM25CGV N. A. N. A. Approved [36]
Methotrexate DM2TEOL Anterior urethra cancer Approved [37]
Deoxycholic acid DM3GYAL Subcutaneous fat disorder EF02 Approved [38]
Quercetin DM3NC4M Obesity 5B81 Approved [39]
Hydroquinone DM6AVR4 Melasma ED60.1 Approved [40]
Marinol DM70IK5 Anorexia nervosa cachexia 6B80 Approved [41]
Ciclosporin DMAZJFX Graft-versus-host disease 4B24 Approved [42]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [43]
Demecolcine DMCZQGK Solid tumour/cancer 2A00-2F9Z Approved [44]
Ivermectin DMDBX5F Intestinal strongyloidiasis due to nematode parasite 1F6B Approved [45]
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Drug(s) Affected By Caspase-9 (CASP9)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Lovastatin DM9OZWQ Arteriosclerosis BD40 Approved [46]
Mannitol DMSCDY9 Bronchiectasis CA24 Approved [47]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [48]
Mechlorethamine DM0CVXA Chronic myelogenous leukaemia 2A20.0 Approved [49]
Leuprorelin acetate DM15HAT Prostate cancer 2C82.0 Approved [50]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [51]
Nitric Oxide DM1RBYG Hypertension BA00-BA04 Approved [52]
Meloxicam DM2AR7L Arthritis FA20 Approved [53]
Ciprofloxacin XR DM2NLS9 Acute gonococcal cervicitis Approved [54]
Colchicine DM2POTE Acute gout flare FA25.0 Approved [55]
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Drug(s) Affected By GTP-binding protein Rheb (RHEB)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [56]
Ivermectin DMDBX5F Intestinal strongyloidiasis due to nematode parasite 1F6B Approved [45]
Pioglitazone DMKJ485 Amyotrophic lateral sclerosis 8B60.0 Approved [57]
Cupric Sulfate DMP0NFQ Fungal infection 1F29-1F2F Approved [58]
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [59]
Phenobarbital DMXZOCG Cluster headache 8A81.0 Approved [60]
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [7]
Zarnestra DMF30HL Acute myeloid leukaemia 2A60 Phase 3 [7]
Benzo(a)pyrene DMN7J43 N. A. N. A. Phase 1 [61]
bisphenol A DM2ZLD7 Discovery agent N.A. Investigative [62]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas
Download the Complete Interaction Atlas for Visualization in Cytoscape

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

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [5]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [5]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Protein Interaction/Cellular Processes [6]
GTP-binding protein Rheb (RHEB) OTFLTSEC RHEB_HUMAN Gene/Protein Processing [7]
Prelamin-A/C (LMNA) OT3SG7ZR LMNA_HUMAN Post-Translational Modifications [8]

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 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. Blood. 2005 Dec 15;106(13):4322-9. doi: 10.1182/blood-2005-06-2584. Epub 2005 Aug 23.
7 Ras homologue enriched in brain is a critical target of farnesyltransferase inhibitors in non-small cell lung cancer cells. Cancer Lett. 2010 Nov 1;297(1):117-25. doi: 10.1016/j.canlet.2010.05.004.
8 Inhibitors of the mevalonate pathway as potential therapeutic agents in multiple myeloma. Leuk Res. 2007 Mar;31(3):341-52. doi: 10.1016/j.leukres.2006.07.018. Epub 2006 Sep 22.
9 Tipifarnib in the treatment of newly diagnosed acute myelogenous leukemia. Biologics. 2008 Sep;2(3):491-500.
10 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.
11 Company report (Prescient)
12 Farnesyltransferase inhibitor BMS-214662 induces apoptosis in B-cell chronic lymphocytic leukemia cells. Leukemia. 2004 Oct;18(10):1599-604.
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15 A novel metal-chelating inhibitor of protein farnesyltransferase. Bioorg Med Chem Lett. 2003 May 5;13(9):1523-6.
16 Tricyclic farnesyl protein transferase inhibitors: crystallographic and calorimetric studies of structure-activity relationships. J Med Chem. 1999 Jun 17;42(12):2125-35.
17 Novel conformationally extended naphthalene-based inhibitors of farnesyltransferase. J Med Chem. 1997 Jun 6;40(12):1763-7.
18 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.
19 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
20 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.
21 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
22 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.
23 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.
24 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
25 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.
26 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.
27 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.
28 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.
29 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.
30 Drug Interactions Flockhart Table
31 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.
32 Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
33 Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
34 Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
35 Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.
36 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
37 Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
38 Prevention of deoxycholate-induced gastric apoptosis by aspirin: roles of NF-kappaB and PKC signaling. J Surg Res. 2008 Mar;145(1):66-73. doi: 10.1016/j.jss.2007.04.039. Epub 2007 Jul 20.
39 Identification of biomarkers for the initiation of apoptosis in human preneoplastic colonocytes by proteome analysis. Int J Cancer. 2004 Mar 20;109(2):220-9. doi: 10.1002/ijc.11692.
40 [Differential proteomic expression in human liver cells stimulated by hydroquinone]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2006 Nov;24(11):658-61.
41 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
42 Proteomics investigations of drug-induced hepatotoxicity in HepG2 cells. Toxicol Sci. 2011 Mar;120(1):109-22.
43 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
44 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
45 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
46 Lovastatin induces apoptosis of anaplastic thyroid cancer cells via inhibition of protein geranylgeranylation and de novo protein synthesis. Endocrinology. 2003 Sep;144(9):3852-9. doi: 10.1210/en.2003-0098.
47 Insulin-like growth factor I prevents mannitol-induced degradation of focal adhesion kinase and Akt. J Biol Chem. 2002 Jul 26;277(30):27393-400. doi: 10.1074/jbc.M201963200. Epub 2002 May 14.
48 Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
49 Inhibition of caspase-dependent mitochondrial permeability transition protects airway epithelial cells against mustard-induced apoptosis. Apoptosis. 2006 Sep;11(9):1545-59. doi: 10.1007/s10495-006-8764-1.
50 Effects of gonadotrophin-releasing hormone agonists on apoptosis of granulosa cells. Ann N Y Acad Sci. 2005 May;1042:531-7. doi: 10.1196/annals.1338.065.
51 The effects of quercetin in cultured human RPE cells under oxidative stress and in Ccl2/Cx3cr1 double deficient mice. Exp Eye Res. 2010 Jul;91(1):15-25.
52 Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 1;64(9):3022-9. doi: 10.1158/0008-5472.can-03-1880.
53 Inhibiting AKT signaling pathway with cilostazol and meloxicam synergism for suppressing K562 cells in vitro. J Biochem Mol Toxicol. 2022 Nov;36(11):e23185. doi: 10.1002/jbt.23185. Epub 2022 Aug 3.
54 Ciprofloxacin induces apoptosis and inhibits proliferation of human colorectal carcinoma cells. Br J Cancer. 2002 Feb 1;86(3):443-8. doi: 10.1038/sj.bjc.6600079.
55 Colchicine-induced apoptosis in human normal liver L-02 cells by mitochondrial mediated pathways. Toxicol In Vitro. 2012 Aug;26(5):649-55. doi: 10.1016/j.tiv.2012.01.024. Epub 2012 Feb 8.
56 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
57 Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells. J Biochem Mol Toxicol. 2020 Oct;34(10):e22547. doi: 10.1002/jbt.22547. Epub 2020 Jun 26.
58 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
59 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
60 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
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62 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.