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

General Information of DTT (ID: TTX41N9)

• DTT Name: Tyrosine-protein kinase Kit (KIT) DTT Info
• UniProt ID: KIT_HUMAN
• Gene Name: KIT

Molecule-Related Drug & Molecule List

8 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[1]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[2]
Pexidartinib	DMS2J0Z	Tenosynovial giant cell tumour	2F7B	Approved	[3]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[4]
Regorafenib	DMHSY1I	Metastatic colorectal cancer	2B91	Approved	[4]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[5]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[6]
Sorafenib	DMS8IFC	Hepatocellular carcinoma	2C12.02	Approved	[7], [8]

7 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
MP470	DMELUAK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[10], [11]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[12]
PLX9486	DM5DZEL	Gastrointestinal stromal tumour	2B5B	Phase 1/2	[13]
AMG-191	DMSHK23	Inflammation	1A00-CA43.1	Phase 1	[14]
CART-117 cells	DMAKZTW	Acute myeloid leukaemia	2A60	Phase 1	[15]
OSI-930	DMF2CZ9	Solid tumour/cancer	2A00-2F9Z	Phase 1	[16], [17]

7 Patented Agent(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID25656651-Compound-21a	DMCKAON	N. A.	N. A.	Patented	[18]
PMID25656651-Compound-21b	DMVABXI	N. A.	N. A.	Patented	[18]
Pyridine derivative 18	DMBZMYT	N. A.	N. A.	Patented	[19]
Pyridine derivative 19	DMXYT40	N. A.	N. A.	Patented	[19]
Pyridine derivative 20	DMAOF0W	N. A.	N. A.	Patented	[19]
Pyridine derivative 21	DMF3907	N. A.	N. A.	Patented	[19]
Pyridine derivative 22	DMSIERF	N. A.	N. A.	Patented	[19]

1 Discontinued Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Motesanib	DMZAL8C	Non-small-cell lung cancer	2C25.Y	Discontinued in Phase 3	[20], [21], [22]

1 Preclinical Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CAR-T cells targeting CD117	DM9HG6S	Acute myeloid leukaemia	2A60	Preclinical	[23]

17 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
4-(4-aminophenyl)-1H-indazol-3yl-amine	DMK1IWD	Discovery agent	N.A.	Investigative	[24]
5,11-Dimethyl-6H-pyrido[4,3-b]carbazol-9-ol	DMWSLTB	Discovery agent	N.A.	Investigative	[25]
9-Bromo-5,11-dimethyl-6H-pyrido[4,3-b]carbazole	DMQEO7F	Discovery agent	N.A.	Investigative	[25]
9-Methoxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole	DMDW267	Discovery agent	N.A.	Investigative	[25]
APCK-110	DMNQ9M1	Solid tumour/cancer	2A00-2F9Z	Investigative	[26]
AST-487	DME76KU	Discovery agent	N.A.	Investigative	[27]
Bis-(5-hydroxy-1H-indol-2-yl)-methanone	DMTSEXB	Discovery agent	N.A.	Investigative	[28]
CP-673451	DMVBPRO	Discovery agent	N.A.	Investigative	[29]
GTP-14564	DMW23Y9	Discovery agent	N.A.	Investigative	[30]
JNJ-28312141	DMCMH7O	Discovery agent	N.A.	Investigative	[31]
Ki-20227	DM9M3VC	Discovery agent	N.A.	Investigative	[32]
PD-0166326	DMD2CG9	Discovery agent	N.A.	Investigative	[33]
PD-0173956	DM8RW92	Discovery agent	N.A.	Investigative	[33]
Phosphonotyrosine	DM09MY1	Discovery agent	N.A.	Investigative	[34]
PMID22765894C8h	DMH5RFU	Discovery agent	N.A.	Investigative	[35]
PMID23521020C7k	DMPCTED	Discovery agent	N.A.	Investigative	[36]
WBZ-7	DME10AL	Solid tumour/cancer	2A00-2F9Z	Investigative	[26]

References

• [1] 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.
• [2] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [6] 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.
• [7] 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.
• [8] Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. Methods Enzymol. 2006;407:597-612.
• [9] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [10] Phase 1B study of amuvatinib in combination with five standard cancer therapies in adults with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Jul;74(1):195-204.
• [11] The receptor tyrosine kinase inhibitor amuvatinib (MP470) sensitizes tumor cells to radio- and chemo-therapies in part by inhibiting homologous recombination. Radiother Oncol. 2011 Oct;101(1):59-65.
• [12] National Cancer Institute Drug Dictionary (drug id 452042).
• [13] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [14] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029529)
• [15] ClinicalTrials.gov (NCT03291444) CAR-T Cells Combined With Peptide Specific Dendritic Cell in Relapsed/Refractory Leukemia/MDS
• [16] OSI-930 analogues as novel reversal agents for ABCG2-mediated multidrug resistance. Biochem Pharmacol. 2012 Sep 15;84(6):766-74.
• [17] Inhibition of c-Kit, VEGFR-2 (KDR), and ABCG2 by analogues of OSI-930. Bioorg Med Chem Lett. 2011 Nov 1;21(21):6495-9.
• [18] Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
• [19] RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99.
• [20] Clinical pipeline report, company report or official report of Amgen (2009).
• [21] Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. J Clin Oncol. 2009 Aug 10;27(23):3794-801.
• [22] Axitinib for renal cell carcinoma. Expert Opin Investig Drugs. 2008 May;17(5):741-8.
• [23] ClinicalTrials.gov (NCT03473457) CAR-T Cells Therapy in Relapsed/Refractory Acute Myeloid Leukemia
• [24] Discovery of N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N'-(2-fluoro-5-methylphenyl)urea (ABT-869), a 3-aminoindazole-based orally active multitargeted ... J Med Chem. 2007 Apr 5;50(7):1584-97.
• [25] Molecular modeling of wild-type and D816V c-Kit inhibition based on ATP-competitive binding of ellipticine derivatives to tyrosine kinases. J Med Chem. 2005 Oct 6;48(20):6194-201.
• [26] 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: 1805).
• [27] The RET kinase inhibitor NVP-AST487 blocks growth and calcitonin gene expression through distinct mechanisms in medullary thyroid cancer cells. Cancer Res. 2007 Jul 15;67(14):6956-64.
• [28] Novel bis(1H-indol-2-yl)methanones as potent inhibitors of FLT3 and platelet-derived growth factor receptor tyrosine kinase. J Med Chem. 2006 Jun 1;49(11):3101-15.
• [29] Antiangiogenic and antitumor activity of a selective PDGFR tyrosine kinase inhibitor, CP-673,451. Cancer Res. 2005 Feb 1;65(3):957-66.
• [30] 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.
• [31] JNJ-28312141, a novel orally active colony-stimulating factor-1 receptor/FMS-related receptor tyrosine kinase-3 receptor tyrosine kinase inhibitor with potential utility in solid tumors, bone metastases, and acute myeloid leukemia. Mol Cancer Ther. 2009 Nov;8(11):3151-61.
• [32] 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.
• [33] Structure-activity relationships of 6-(2,6-dichlorophenyl)-8-methyl-2-(phenylamino)pyrido[2,3-d]pyrimidin-7-ones: toward selective Abl inhibitors. Bioorg Med Chem Lett. 2009 Dec 15;19(24):6872-6.
• [34] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [35] The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett. 2012 Aug 1;22(15):4979-85.
• [36] Discovery and optimization of 3-(2-(Pyrazolo[1,5-a]pyrimidin-6-yl)ethynyl)benzamides as novel selective and orally bioavailable discoidin domain receptor 1 (DDR1) inhibitors. J Med Chem. 2013 Apr 25;56(8):3281-95.