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

General Information of Drug (ID: DM9M3VC)

• Drug Name: Ki-20227 Drug Info
• Synonyms: Ki 20227; Ki20227

Indication

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

• Cross-matching ID:
  PubChem CID: 9869779
  CAS Number: CAS 623142-96-1
  TTD Drug ID: DM9M3VC

Molecule-Related Drug Atlas

Drug(s) Targeting CSF1R messenger RNA (CSF1R mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
JNJ-28312141	DMCMH7O	Discovery agent	N.A.	Investigative	[2]
GTP-14564	DMW23Y9	Discovery agent	N.A.	Investigative	[3]
GW-2580	DMTW9GM	Discovery agent	N.A.	Investigative	[4]

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	[5]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[6]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[7]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[8]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[8]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[9]
Pexidartinib	DMS2J0Z	Tenosynovial giant cell tumour	2F7B	Approved	[10]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[11]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[12]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[13]

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	[6]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[14]
Becaplermin	DM1R5X4	Diabetic complication	5A2Y	Approved	[15]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[16]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[12]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[13]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[17]
SNN-0031	DM2X3BR	Brain injury	NA07.Z	Phase 1/2	[18]
TAK-593	DMNFZOT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[19]
Pyridine derivative 18	DMBZMYT	N. A.	N. A.	Patented	[20]

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	[6]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[21]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[8]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[22]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[23]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[5]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[9]
Fruquintinib	DMHOSCQ	Colorectal cancer	2B91.Z	Approved	[24]
Cabozantinib	DMIYDT4	Medullary thyroid gland carcinoma		Approved	[25]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[26]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
CSF1R messenger RNA (CSF1R mRNA)	TTVW6QL	CSF1R_HUMAN	Inhibitor	[2]
Platelet-derived growth factor receptor beta (PDGFRB)	TTI7421	PGFRB_HUMAN	Inhibitor	[1]
Tyrosine-protein kinase Kit (KIT)	TTX41N9	KIT_HUMAN	Inhibitor	[1]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[1]

References

• [1] A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. Mol Cancer Ther. 2006 Nov;5(11):2634-43.
• [2] Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011 Oct 30;29(11):1046-51.
• [3] Selective cytotoxic mechanism of GTP-14564, a novel tyrosine kinase inhibitor in leukemia cells expressing a constitutively active Fms-like tyrosin... J Biol Chem. 2003 Aug 29;278(35):32892-8.
• [4] Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580. Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):16078-83.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [9] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [12] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [13] National Cancer Institute Drug Dictionary (drug id 452042).
• [14] 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.
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [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] MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
• [18] Company report (Neuronova)
• [19] 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.
• [20] RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99.
• [21] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [22] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [23] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [24] 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.
• [25] Clinical pipeline report, company report or official report of Exelixis (2011).
• [26] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services