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

General Information of Drug (ID: DMNV0EZ)

• Drug Name: 3,6-Di-pyridin-4-yl-pyrazolo[1,5-a]pyrimidine Drug Info
• Synonyms: pyrazolo[1,5-a]pyrimidine 1a; AC1NS6UW; CHEMBL92279; BDBM5417; 3,6-dipyridin-4-ylpyrazolo[1,5-a]pyrimidine; 3,6-Bis(4-pyridyl)pyrazolo[1,5-a]pyrimidine

Indication

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

• Cross-matching ID:
  PubChem CID: 5329454
  TTD Drug ID: DMNV0EZ

Molecule-Related Drug Atlas

Drug(s) Targeting Vascular endothelial growth factor receptor 3 (FLT-4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fruquintinib	DMHOSCQ	Colorectal cancer	2B91.Z	Approved	[3]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[4]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[5]
Sulfatinib	DMPOTM4	Neuroendocrine cancer	2B72.1	Phase 3	[6]
PI-88	DMGZPX6	Hepatocellular carcinoma	2C12.02	Phase 3	[7]
Taberminogene vadenovec	DMW5PHL	Vascular restinosis	BE2Z	Phase 3	[8]
ABT-869	DMREDYP	Solid tumour/cancer	2A00-2F9Z	Phase 3	[9]
MGCD516	DM752PU	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[10]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[11]
VATALANIB	DMY0UEQ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[12]

Drug(s) Targeting VEGFR1 messenger RNA (VEGFR1 mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[13]
VATALANIB	DMY0UEQ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[14]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[15]
Sirna-027	DMZTQD8	Exudative age-related macular degeneration	9B78.3Z	Phase 1/2	[16]
PMID22765894C8h	DMH5RFU	Discovery agent	N.A.	Investigative	[17]
2-(1H-indazol-3-yl)-1H-benzo[d]imidazole	DM0CSH8	Discovery agent	N.A.	Investigative	[18]
AAL-993	DM35RFH	Discovery agent	N.A.	Investigative	[14]
PMID17935989C25	DML8ZBR	Discovery agent	N.A.	Investigative	[19]
2-(5-Phenyl-oxazol-2-ylamino)-benzonitrile	DMX6QMT	Discovery agent	N.A.	Investigative	[12]
4-Chloro-N-(3-chloro-benzoyl)-benzenesulfonamide	DMI3OR9	Discovery agent	N.A.	Investigative	[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	[21]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[22]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[23]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[24]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[25]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[26]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[27]
Fruquintinib	DMHOSCQ	Colorectal cancer	2B91.Z	Approved	[3]
Cabozantinib	DMIYDT4	Medullary thyroid gland carcinoma		Approved	[28]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[4]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[1]
Vascular endothelial growth factor receptor 3 (FLT-4)	TTDCBX5	VGFR3_HUMAN	Inhibitor	[2]
VEGFR1 messenger RNA (VEGFR1 mRNA)	TT1VAUK	VGFR1_HUMAN	Inhibitor	[2]

References

• [1] Optimization of a pyrazolo[1,5-a]pyrimidine class of KDR kinase inhibitors: improvements in physical properties enhance cellular activity and pharm... Bioorg Med Chem Lett. 2002 Dec 16;12(24):3537-41.
• [2] Synthesis and initial SAR studies of 3,6-disubstituted pyrazolo[1,5-a]pyrimidines: a new class of KDR kinase inhibitors. Bioorg Med Chem Lett. 2002 Oct 7;12(19):2767-70.
• [3] 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.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [5] 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.
• [6] Clinical pipeline report, company report or official report of Hutchison Medi Pharma.
• [7] Company report (Medigen)
• [8] Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
• [9] Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol Cancer Ther. 2006 Apr;5(4):995-1006.
• [10] 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: 1814).
• [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] Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors. J Med Chem. 2005 Mar 10;48(5):1610-9.
• [13] 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.
• [14] Inhibitors of VEGF receptors-1 and -2 based on the 2-((pyridin-4-yl)ethyl)pyridine template. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1913-9.
• [15] MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
• [16] 2011 Pipeline of Sirna Therapeutics.
• [17] The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett. 2012 Aug 1;22(15):4979-85.
• [18] Design and structure-activity relationship of 3-benzimidazol-2-yl-1H-indazoles as inhibitors of receptor tyrosine kinases. Bioorg Med Chem Lett. 2006 Jul 1;16(13):3595-9.
• [19] Macrocyclic ureas as potent and selective Chk1 inhibitors: an improved synthesis, kinome profiling, structure-activity relationships, and prelimina... Bioorg Med Chem Lett. 2007 Dec 1;17(23):6593-601.
• [20] Acyl sulfonamide anti-proliferatives: benzene substituent structure-activity relationships for a novel class of antitumor agents. J Med Chem. 2004 Oct 21;47(22):5367-80.
• [21] 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.
• [22] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [23] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [24] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [25] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [26] 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.
• [27] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [28] Clinical pipeline report, company report or official report of Exelixis (2011).