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

General Information of Drug (ID: DMT3ML6)

• Drug Name: AG-213 Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 667601
  ChEBI ID: CHEBI:93703
  CAS Number: CAS 122520-86-9
  TTD Drug ID: DMT3ML6

Molecule-Related Drug Atlas

Drug(s) Targeting Epidermal growth factor receptor (EGFR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[3]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[4]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[5]
Erlotinib	DMCMBHA	Adrenal gland neoplasm		Approved	[6]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[7]
Dacomitinib	DMOH8VY	Non-small-cell lung cancer	2C25.Y	Approved	[8]
BIBW 2992	DMTKD7Q	Non-small-cell lung cancer	2C25.Y	Approved	[9]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[10]
Epidermal growth factor	DMVONE6	Vulnerary	ND56.Z	Approved	[8]
Merimepodib	DM0HS92	Breast cancer	2C60-2C65	Approved	[11]

Drug(s) Targeting ERBB2 messenger RNA (HER2 mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
HKI-272	DM6QOVN	Breast cancer	2C60-2C65	Phase 3	[12]
BMS-690514	DMX302C	Chronic pain	MG30	Phase 2	[13]
3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione	DMDO175	Discovery agent	N.A.	Investigative	[14]
3,4-diphenyl-1H-pyrrole-2,5-dione	DMPK6YT	Discovery agent	N.A.	Investigative	[14]
3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione	DMGC7RY	Discovery agent	N.A.	Investigative	[14]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[15]
3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione	DM3EV9N	Discovery agent	N.A.	Investigative	[14]
PMID24915291C38	DMBXT9J	Discovery agent	N.A.	Investigative	[16]
Geldanamycin-estradiol hybrid	DMUSJ96	Discovery agent	N.A.	Investigative	[17]
CL-387785	DMLKFZC	Discovery agent	N.A.	Investigative	[18]

Drug(s) Affected By Voltage-dependent T-type calcium channel subunit alpha-1H (CACNA1H)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Herbimycin A	DM6YWBF	Solid tumour/cancer	2A00-2F9Z	Approved	[2]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[19]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[20]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[21]
Menthol	DMG2KW7	Back pain	ME84.Z	Approved	[22]
Niclosamide	DMJAGXQ	Cestodes infection	1F70-1F76	Approved	[23]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[24]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[25]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[26]
Triclosan	DMZUR4N	Malaria	1F40-1F45	Approved	[27]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[1]
ERBB2 messenger RNA (HER2 mRNA)	TTR5TV4	ERBB2_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Voltage-dependent T-type calcium channel subunit alpha-1H (CACNA1H)	OTM705TH	CAC1H_HUMAN	Gene/Protein Processing	[2]

References

• [1] Syntheses of 4-(indole-3-yl)quinazolines: a new class of epidermal growth factor receptor tyrosine kinase inhibitors. Eur J Med Chem. 2008 Jul;43(7):1478-88.
• [2] Regulation of CA(v)3.2 Ca2+ channel activity by protein tyrosine phosphorylation. J Microbiol Biotechnol. 2008 Feb;18(2):365-8.
• [3] Nasopharyngeal carcinoma: Current treatment options and future directions. J Nasopharyng Carcinoma, 2014, 1(16): e16.
• [4] Triple negative breast cancer--current status and prospective targeted treatment based on HER1 (EGFR), TOP2A and C-MYC gene assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009 Mar;153(1):13-7.
• [5] Gefitinib ('Iressa', ZD1839) and new epidermal growth factor receptor inhibitors. Br J Cancer. 2004 Feb 9;90(3):566-72.
• [6] Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
• [7] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [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: 1797).
• [9] Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
• [10] Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles. J Med Chem. 2006 Dec 28;49(26):7868-76.
• [11] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [12] Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling. Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19936-41.
• [13] Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2. J Pharm Sci. 2010 Aug;99(8):3579-93.
• [14] Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81.
• [15] Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitum... J Med Chem. 2005 Sep 8;48(18):5639-43.
• [16] Discovery of a series of 2,5-diaminopyrimidine covalent irreversible inhibitors of Bruton's tyrosine kinase with in vivo antitumor activity. J Med Chem. 2014 Jun 26;57(12):5112-28.
• [17] Synthesis and evaluation of geldanamycin-estradiol hybrids. Bioorg Med Chem Lett. 1999 May 3;9(9):1233-8.
• [18] Tyrosine kinase inhibitors. 19. 6-Alkynamides of 4-anilinoquinazolines and 4-anilinopyrido[3,4-d]pyrimidines as irreversible inhibitors of the erbB... J Med Chem. 2006 Feb 23;49(4):1475-85.
• [19] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [20] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [21] 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.
• [22] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [23] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [24] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [25] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [26] 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.
• [27] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.