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

General Information of Drug (ID: DME76KU)

• Drug Name: AST-487 Drug Info
• Synonyms: AST 487; NVP-AST 487; NVP-AST487

Indication

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

• Cross-matching ID:
  PubChem CID: 11409972
  CAS Number: CAS 630124-46-8
  TTD Drug ID: DME76KU

Molecule-Related Drug Atlas

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	[4]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[5]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[6]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[7]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[7]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[8]
Pexidartinib	DMS2J0Z	Tenosynovial giant cell tumour	2F7B	Approved	[9]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[10]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[11]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[12]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[13]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[7]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[7]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[4]
Selpercatinib	DMZR15V	Non-small-cell lung cancer	2C25.Y	Approved	[14]
Pralsetinib	DMWU0I2	Non-small-cell lung cancer	2C25.Y	Approved	[15]
MGCD516	DM752PU	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[16]
CEP-32496	DMAO04B	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[17]
TPX-0046	DMIVE67	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[18]
GSK3179106	DM2KCIP	Inflammatory bowel disease	DD72	Phase 1	[19]

Drug(s) Targeting Fms-like tyrosine kinase 3 (FLT-3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[20]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[7]
Intedanib	DMSTA36	Colorectal cancer	2B91.Z	Approved	[21]
Midostaurin	DMI6E0R	Acute myeloid leukaemia	2A60	Approved	[4]
Gilteritinib	DMTI0ZO	Acute myeloid leukaemia	2A60	Approved	[22]
Pexidartinib	DMS2J0Z	Tenosynovial giant cell tumour	2F7B	Approved	[9]
Pacritinib	DM1T6ZN	Myelofibrosis	2A20.2	Approved	[20]
Quizartinib	DM8Y4JS	Acute myeloid leukaemia	2A60	Approved	[17]
Lestaurtinib	DMQ2AIJ	Acute myeloid leukaemia	2A60	Approved (orphan drug)	[23]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[11]

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	[5]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[24]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[7]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[25]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[26]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[4]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[8]
Fruquintinib	DMHOSCQ	Colorectal cancer	2B91.Z	Approved	[27]
Cabozantinib	DMIYDT4	Medullary thyroid gland carcinoma		Approved	[28]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fms-like tyrosine kinase 3 (FLT-3)	TTGJCWZ	FLT3_HUMAN	Inhibitor	[2]
Proto-oncogene c-Ret (RET)	TT4DXQT	RET_HUMAN	Inhibitor	[3]
Tyrosine-protein kinase Kit (KIT)	TTX41N9	KIT_HUMAN	Inhibitor	[3]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[3]

References

• [1] Antileukemic effects of the novel, mutant FLT3 inhibitor NVP-AST487: effects on PKC412-sensitive and -resistant FLT3-expressing cells. Blood. 2008 Dec 15;112(13):5161-70.
• [2] Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011 Oct 30;29(11):1046-51.
• [3] 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.
• [4] 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.
• [5] 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.
• [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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [8] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [11] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [12] National Cancer Institute Drug Dictionary (drug id 452042).
• [13] 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.
• [14] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [16] 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).
• [17] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [18] Clinical pipeline report, company report or official report of Turning Point Therapeutics.
• [19] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [20] 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: 1807).
• [21] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [22] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [23] Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with ... Blood. 2008 Jun 15;111(12):5663-71.
• [24] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [25] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [26] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [27] 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.
• [28] Clinical pipeline report, company report or official report of Exelixis (2011).
• [29] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services