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

General Information of Drug (ID: DMCKAON)

• Drug Name: PMID25656651-Compound-21a Drug Info
• Cross-matching ID:
  PubChem CID: 44225624
  TTD Drug ID: DMCKAON

Molecule-Related Drug Atlas

Drug(s) Targeting Fusion protein Bcr-Abl (Bcr-Abl)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[2]
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[2]
Nilotinib	DM7HXWT	Chronic myelogenous leukaemia	2A20.0	Approved	[3]
Asciminib	DM7EVUF	Chronic myeloid leukaemia	2A20	Approved	[4]
Radotinib	DMWA74Y	leukaemia	2A60-2B33	Phase 3	[5]
ABL 001	DMMF5K4	Chronic myeloid leukaemia	2A20	Phase 3	[6]
ICLUSIG	DM1SQSE	Acute lymphoblastic leukaemia	2A85	Phase 3	[7]
Bafetinib	DM7586F	Bone disease	FC0Z	Phase 2	[8]
AN-019	DMJ7QP8	Chronic myelogenous leukaemia	2A20.0	Phase 2	[9]
HQP1351	DMQ30X2	Chronic myeloid leukaemia	2A20	Phase 2	[10]

Drug(s) Targeting Tyrosine-protein kinase Kit (KIT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[2]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[11]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[12]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[13]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[13]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[14]
Pexidartinib	DMS2J0Z	Tenosynovial giant cell tumour	2F7B	Approved	[15]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[16]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[17]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[18]

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	[11]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[19]
Becaplermin	DM1R5X4	Diabetic complication	5A2Y	Approved	[20]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[21]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[17]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[18]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[22]
SNN-0031	DM2X3BR	Brain injury	NA07.Z	Phase 1/2	[23]
TAK-593	DMNFZOT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[24]
Pyridine derivative 18	DMBZMYT	N. A.	N. A.	Patented	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fusion protein Bcr-Abl (Bcr-Abl)	TTS7G69	BCR_HUMAN-ABL1_HUMAN	Inhibitor	[1]
Platelet-derived growth factor receptor beta (PDGFRB)	TTI7421	PGFRB_HUMAN	Inhibitor	[1]
Tyrosine-protein kinase Kit (KIT)	TTX41N9	KIT_HUMAN	Inhibitor	[1]

References

• [1] Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
• [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] 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
• [4] Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure. N Engl J Med. 2019 Dec 12;381(24):2315-2326.
• [5] Danusertib, an aurora kinase inhibitor.Expert Opin Investig Drugs.2012 Mar;21(3):383-93.
• [6] ABL001, a Potent Allosteric Inhibitor of BCR-ABL, Prevents Emergence of Resistant Disease When Administered in Combination with Nilotinib in an in Vivo Murine Model of Chronic Myeloid Leukemia, NorthBuilding, 2014, 120-125.
• [7] Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. Blood. 2018 Jul 26;132(4):393-404.
• [8] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [9] Design, synthesis and preclinical evaluation of NRC-AN-019. Int J Oncol. 2013 Jan;42(1):168-78.
• [10] Preclinical development of HQP1351, a multikinase inhibitor targeting a broad spectrum of mutant KIT kinases, for the treatment of imatinib-resistant gastrointestinal stromal tumors. Cell Biosci. 2019 Oct 26;9:88.
• [11] 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.
• [12] New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven a... J Med Chem. 2000 Jun 15;43(12):2310-23.
• [13] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [14] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [16] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [17] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [18] National Cancer Institute Drug Dictionary (drug id 452042).
• [19] 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.
• [20] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [21] 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.
• [22] MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
• [23] Company report (Neuronova)
• [24] 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.
• [25] RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99.