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

General Information of Drug (ID: DMIR3X2)

• Drug Name: TG-100435 Drug Info
• Synonyms: TG-100435; CHEMBL230686; SCHEMBL4266197; ZINC28702706; BDBM50198782; US8481536, 367; US8481536, 575; ([7-(2,6-dichloro-phenyl)-5-methyl-benzo[1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-amine); 7-(2,6-dichlorophenyl)-5-methyl-N-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)benzo[e][1,2,4]triazin-3-amine

Indication

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

• Cross-matching ID:
  PubChem CID: 11562302
  CAS Number: CAS 867330-68-5
  TTD Drug ID: DMIR3X2

Molecule-Related Drug Atlas

Drug(s) Targeting LCK tyrosine protein kinase (LCK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[2]
VX-680	DM93YKJ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]
JNJ-26483327	DMSQ3AZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]
ISIS-CRP	DMQDUG4	Cardiovascular disease	BA00-BE2Z	Phase 1	[4]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[5]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[5]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[6]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[5]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[7]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[8]

Drug(s) Targeting Ephrin type-B receptor 4 (EPHB4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
KD019	DMEFW3G	Brain metastases	2D50	Phase 2	[9]
PMID23489211C20	DMDYC4J	Discovery agent	N.A.	Investigative	[10]
PMID19788238C66	DMCVJK9	Discovery agent	N.A.	Investigative	[11]
EphB4-131	DM3F427	Solid tumour/cancer	2A00-2F9Z	Investigative	[12]

Drug(s) Targeting Fibroblast growth factor receptor 2 (FGFR2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pemigatinib	DM819JF	Cholangiocarcinoma	2C12.10	Approved	[13]
Interferon Alfa-2a, Recombinant	DMUTZ8S	Chronic HCV-1 infection	1E51.1	Approved	[14]
Palifermin	DM9JOYP	Oral mucositis	DA01.11	Approved	[15]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[16]
Trafermin	DMLKI2B	Periodontitis	DA0C	Phase 3	[17]
Debio 1347	DMZW50O	Solid tumour/cancer	2A00-2F9Z	Phase 2	[18]
LY2874455	DMZ0DMY	Solid tumour/cancer	2A00-2F9Z	Phase 2	[19]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[20]
AEE-788	DMEOS5K	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[2]
BAY1179470	DM7L91K	Solid tumour/cancer	2A00-2F9Z	Phase 1	[21]

Drug(s) Targeting Platelet-derived growth factor receptor beta (PDGFRB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[22]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[23]
Becaplermin	DM1R5X4	Diabetic complication	5A2Y	Approved	[24]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[16]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[25]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[26]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[20]
SNN-0031	DM2X3BR	Brain injury	NA07.Z	Phase 1/2	[27]
TAK-593	DMNFZOT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[28]
Pyridine derivative 18	DMBZMYT	N. A.	N. A.	Patented	[29]

Drug(s) Targeting Proto-oncogene c-Ret (RET)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[30]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[31]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[31]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[2]
Selpercatinib	DMZR15V	Non-small-cell lung cancer	2C25.Y	Approved	[32]
Pralsetinib	DMWU0I2	Non-small-cell lung cancer	2C25.Y	Approved	[33]
MGCD516	DM752PU	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[34]
CEP-32496	DMAO04B	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[18]
TPX-0046	DMIVE67	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[35]
GSK3179106	DM2KCIP	Inflammatory bowel disease	DD72	Phase 1	[36]

Drug(s) Targeting Tyrosine-protein kinase ABL1 (ABL)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[31]
Bosutinib	DMTI8YE	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[2]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[37]
Adenosine triphosphate	DM79F6G	Malnutrition	5B50-5B71	Approved	[38]
Saracatinib	DMBLHGP	Hematologic tumour	2B33.Y	Phase 2	[39]
Flumatinib	DM0G5O6	Chronic myelogenous leukaemia	2A20.0	Phase 2	[40]
DCC-2036	DMJKFNU	Chronic myeloid leukaemia	2A20	Phase 1/2	[41]
ISIS-CRP	DMQDUG4	Cardiovascular disease	BA00-BE2Z	Phase 1	[42]
KW-2449	DMFO7RP	Acute myeloid leukaemia	2A60	Phase 1	[43]
IkT-148009	DMMJ9HY	Parkinson disease	8A00.0	Phase 1	[44]

Drug(s) Targeting Yes tyrosine kinase (YES)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
JNJ-26483327	DMSQ3AZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]

Drug(s) Targeting Vascular endothelial growth factor receptor 2 (KDR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[22]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[45]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[31]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[46]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[47]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[2]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[48]
Fruquintinib	DMHOSCQ	Colorectal cancer	2B91.Z	Approved	[49]
Cabozantinib	DMIYDT4	Medullary thyroid gland carcinoma		Approved	[50]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[51]

Drug(s) Targeting Proto-oncogene c-Src (SRC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[2]
Bosutinib	DMTI8YE	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[2]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[37]
Herbimycin A	DM6YWBF	Solid tumour/cancer	2A00-2F9Z	Approved	[52]
AL3818	DM3WP0N	Alveolar soft part sarcoma	2A60-2C35	Phase 3	[18]
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[18]
Masitinib	DMRSNEU	Amyotrophic lateral sclerosis	8B60.0	Phase 3	[36]
KX-01	DMF0NA9	Actinic keratosis	EK90.0	Phase 3	[53]
Saracatinib	DMBLHGP	Hematologic tumour	2B33.Y	Phase 2	[39]
TPX-0046	DMIVE67	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[35]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Ephrin type-B receptor 4 (EPHB4)	TTI4ZX2	EPHB4_HUMAN	Inhibitor	[1]
Fibroblast growth factor receptor 2 (FGFR2)	TTGJVQM	FGFR2_HUMAN	Inhibitor	[1]
LCK tyrosine protein kinase (LCK)	TT860QF	LCK_HUMAN	Inhibitor	[1]
Platelet-derived growth factor receptor beta (PDGFRB)	TTI7421	PGFRB_HUMAN	Inhibitor	[1]
Proto-oncogene c-Ret (RET)	TT4DXQT	RET_HUMAN	Inhibitor	[1]
Proto-oncogene c-Src (SRC)	TT6PKBN	SRC_HUMAN	Inhibitor	[1]
Tyrosine-protein kinase ABL1 (ABL)	TT3PJMV	ABL1_HUMAN	Inhibitor	[1]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[1]
Yes tyrosine kinase (YES)	TT0SQ8J	YES_HUMAN	Inhibitor	[1]

References

• [1] Discovery of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine--a potent, orally active Src kinas... Bioorg Med Chem Lett. 2007 Feb 1;17(3):602-8.
• [2] 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.
• [3] National Cancer Institute Drug Dictionary (drug id 596693).
• [4] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
• [5] Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
• [6] Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
• [7] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [8] 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.
• [9] XL647--a multitargeted tyrosine kinase inhibitor: results of a phase II study in subjects with non-small cell lung cancer who have progressed after responding to treatment with either gefitinib or erlotinib. J Thorac Oncol. 2012 Jan;7(1):219-26.
• [10] Amino acid conjugates of lithocholic acid as antagonists of the EphA2 receptor. J Med Chem. 2013 Apr 11;56(7):2936-47.
• [11] Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4). J Med Chem. 2009 Oct 22;52(20):6433-46.
• [12] 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: 1833).
• [13] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [14] DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
• [15] Keratinocyte growth factor. Expert Opin Biol Ther. 2009 Jun;9(6):779-87.
• [16] E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405.
• [17] Emerging drugs for diabetic foot ulcers. Expert Opin Emerg Drugs. 2006 Nov;11(4):709-24.
• [18] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [19] Company report (Eli Lilly) (drug: LY2874455)
• [20] MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
• [21] National Cancer Institute Drug Dictionary (drug id 751593).
• [22] Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.
• [23] Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel... J Med Chem. 2003 Mar 27;46(7):1116-9.
• [24] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [25] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [26] National Cancer Institute Drug Dictionary (drug id 452042).
• [27] Company report (Neuronova)
• [28] Biochemical characterization of TAK-593, a novel VEGFR/PDGFR inhibitor with a two-step slow binding mechanism. Biochemistry. 2011 Feb 8;50(5):738-51.
• [29] RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99.
• [30] Synthesis, structure-activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors. Bioorg Med Chem. 2010 Feb 15;18(4):1482-96.
• [31] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [32] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [33] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [34] 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: 2185).
• [35] Clinical pipeline report, company report or official report of Turning Point Therapeutics.
• [36] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [37] 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.
• [38] Targeted chronic myeloid leukemia therapy: Seeking a cure. Am J Health Syst Pharm. 2007 Dec 15;64(24 Suppl 15):S9-15.
• [39] Novel dual Src/Abl inhibitors for hematologic and solid malignancies.Expert Opin Investig Drugs.2010 Aug;19(8):931-45.
• [40] Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants. Cancer Sci. 2014 Jan;105(1):117-25.
• [41] Company report (Deciphera Pharmaceuticals: Tumor-Targeted Programs and Indications)
• [42] Structure-based optimization of pyrazolo[3,4-d]pyrimidines as Abl inhibitors and antiproliferative agents toward human leukemia cell lines. J Med Chem. 2008 Mar 13;51(5):1252-9.
• [43] KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood. 2009 Aug 20;114(8):1607-17.
• [44] The c-Abl inhibitor IkT-148009 suppresses neurodegeneration in mouse models of heritable and sporadic Parkinson's disease. Sci Transl Med. 2023 Jan 18;15(679):eabp9352.
• [45] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [46] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [47] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [48] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [49] Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cancer Biol Ther. 2014;15(12):1635-45.
• [50] Clinical pipeline report, company report or official report of Exelixis (2011).
• [51] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [52] In vivo antitumor activity of herbimycin A, a tyrosine kinase inhibitor, targeted against BCR/ABL oncoprotein in mice bearing BCR/ABL-transfected cells. Leuk Res. 1994 Nov;18(11):867-73.
• [53] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)