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

General Information of Drug (ID: DMGM7QD)

• Drug Name: BMS-777607 Drug Info
• Synonyms: BMS-777607; 1025720-94-8; BMS 777607; 1196681-44-3; BMS777607; ASLAN-002; UNII-A3MMS6HDO1; N-(4-(2-Amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; A3MMS6HDO1; N-[4-[(2-Amino-3-chloropyridin-4-yl)oxy]-3-fluorophenyl]-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; N-(4-((2-amino-3-chloropyridin-4-yl)oxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide
• Cross-matching ID:
  PubChem CID: 24794418
  ChEBI ID: CHEBI:91409
  CAS Number: CAS 1025720-94-8
  TTD Drug ID: DMGM7QD

Molecule-Related Drug Atlas

Drug(s) Targeting Proto-oncogene c-Met (MET)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[3]
Cabozantinib	DMIYDT4	Medullary thyroid gland carcinoma		Approved	[4]
Amivantamab	DMZ7AMY	Non-small-cell lung cancer	2C25	Approved	[5]
Capmatinib	DMYCXKL	Non-small-cell lung cancer	2C25.Y	Approved	[6]
Tepotinib	DMUQ0E8	Non-small-cell lung cancer	2C25	Approved	[7]
RG3638	DMTQJE0	Gastric adenocarcinoma	2B72	Phase 3	[8]
Savolitinib	DMALFKX	Renal cell carcinoma	2C90	Phase 3	[9]
Beperminogene perplasmid	DM6RWBN	Critical limb ischemia	BD4Y	Phase 3	[10]
Tivantinib	DMNVP8Q	Hepatocellular carcinoma	2C12.02	Phase 3	[11]
MGCD516	DM752PU	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[8]

Drug(s) Affected By Beta-galactosidase (GLB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[12]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[13]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[14]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[15]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[16]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[17]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[18]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[19]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[20]
Bendamustine hydrochloride	DMFH15Z	leukaemia	2A60-2B33	Approved	[21]

Drug(s) Affected By Cyclin-dependent kinase inhibitor 1 (CDKN1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[22]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[23]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[24]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[25]
Talazoparib	DM1KS78	Breast cancer	2C60-2C65	Approved	[26]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[27]
Etretinate	DM2CZFA	Keratosis	ED56	Approved	[28]
Prednisone	DM2HG4X	Acute asthma	CA23	Approved	[29]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[30]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Proto-oncogene c-Met (MET)	TTNDSF4	MET_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Beta-galactosidase (GLB1)	OTB0TKAG	BGAL_HUMAN	Gene/Protein Processing	[2]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Gene/Protein Processing	[2]

References

• [1] Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607... J Med Chem. 2009 Mar 12;52(5):1251-4.
• [2] Prevention of BMS-777607-induced polyploidy/senescence by mTOR inhibitor AZD8055 sensitizes breast cancer cells to cytotoxic chemotherapeutics. Mol Oncol. 2014 May;8(3):469-82. doi: 10.1016/j.molonc.2013.12.014. Epub 2014 Jan 2.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Clinical pipeline report, company report or official report of Exelixis (2011).
• [5] Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC. Cancer Discov. 2020 Aug;10(8):1194-1209.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [8] 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. (Target id: 1815).
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] Beperminogene perplasmid for the treatment of critical limb ischemia. Expert Rev Cardiovasc Ther. 2014 Oct;12(10):1145-56.
• [11] 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: 7948).
• [12] Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells. Toxicol Sci. 2023 Feb 17;191(2):227-238. doi: 10.1093/toxsci/kfac131.
• [13] PARP1 inhibitor (PJ34) improves the function of aging-induced endothelial progenitor cells by preserving intracellular NAD(+) levels and increasing SIRT1 activity. Stem Cell Res Ther. 2018 Aug 23;9(1):224. doi: 10.1186/s13287-018-0961-7.
• [14] Endothelial cellular senescence is inhibited by nitric oxide: implications in atherosclerosis associated with menopause and diabetes. Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):17018-23. doi: 10.1073/pnas.0607873103. Epub 2006 Oct 30.
• [15] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [16] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [17] Arsenic induces human chondrocyte senescence and accelerates rat articular cartilage aging. Arch Toxicol. 2020 Jan;94(1):89-101. doi: 10.1007/s00204-019-02607-2. Epub 2019 Nov 16.
• [18] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [19] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [20] 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.
• [21] Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard. Arch Toxicol. 2021 Feb;95(2):727-747. doi: 10.1007/s00204-020-02946-5. Epub 2021 Jan 25.
• [22] Zidovudine induces S-phase arrest and cell cycle gene expression changes in human cells. Mutagenesis. 2005 Mar;20(2):139-46. doi: 10.1093/mutage/gei019. Epub 2005 Mar 22.
• [23] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [24] Gene expression profiles with activation of the estrogen receptor alpha-selective estrogen receptor modulator complex in breast cancer cells expressing wild-type estrogen receptor. Cancer Res. 2002 Aug 1;62(15):4419-26.
• [25] Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells. Toxicol Appl Pharmacol. 2017 Nov 15;335:16-27. doi: 10.1016/j.taap.2017.09.017. Epub 2017 Sep 21.
• [26] BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile. J Biochem Mol Toxicol. 2019 May;33(5):e22286. doi: 10.1002/jbt.22286. Epub 2019 Jan 23.
• [27] Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. Cancer Res. 2002 Nov 1;62(21):6246-54.
• [28] Bexarotene activates the p53/p73 pathway in human cutaneous T-cell lymphoma. Br J Dermatol. 2009 Mar;160(3):519-26. doi: 10.1111/j.1365-2133.2008.08931.x. Epub 2008 Nov 25.
• [29] Glucocorticoids induce G1 arrest of lymphoblastic cells through retinoblastoma protein Rb1 dephosphorylation in childhood acute lymphoblastic leukemia in vivo. Cancer Biol Ther. 2004 May;3(5):470-6. doi: 10.4161/cbt.3.5.838. Epub 2004 May 9.
• [30] Ciprofloxacin mediated cell growth inhibition, S/G2-M cell cycle arrest, and apoptosis in a human transitional cell carcinoma of the bladder cell line. Clin Cancer Res. 2000 Mar;6(3):891-900.
• [31] Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.