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

General Information of Drug (ID: DMH5RFU)

• Drug Name: PMID22765894C8h Drug Info
• Synonyms: GTPL8175; BDBM50420996

Indication

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

• Cross-matching ID:
  PubChem CID: 67161540
  TTD Drug ID: DMH5RFU

Molecule-Related Drug Atlas

Drug(s) Targeting Ribosomal protein S6 kinase alpha-3 (RSK3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID27410995-Compound-Figure3j	DMJRZLB	N. A.	N. A.	Patented	[2]
Indole-based analog 14	DMQURWZ	N. A.	N. A.	Patented	[2]
Pyrrolo[2,3-d]pyrimidine derivative 35	DMXU08A	N. A.	N. A.	Patented	[2]
BI-D1870	DMK3SAF	Chronic lymphocytic leukaemia	2A82.0	Preclinical	[3]
PMID22564207C25b	DMBMYKQ	Discovery agent	N.A.	Investigative	[4]
BIX 02565	DMNAX1Q	Discovery agent	N.A.	Investigative	[5]

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	[6]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[7]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[8]
Sulfatinib	DMPOTM4	Neuroendocrine cancer	2B72.1	Phase 3	[9]
PI-88	DMGZPX6	Hepatocellular carcinoma	2C12.02	Phase 3	[10]
Taberminogene vadenovec	DMW5PHL	Vascular restinosis	BE2Z	Phase 3	[11]
ABT-869	DMREDYP	Solid tumour/cancer	2A00-2F9Z	Phase 3	[12]
MGCD516	DM752PU	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[13]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[14]
VATALANIB	DMY0UEQ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[15]

Drug(s) Targeting Fibroblast growth factor receptor 1 (FGFR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[16]
Intedanib	DMSTA36	Colorectal cancer	2B91.Z	Approved	[17]
Pemigatinib	DM819JF	Cholangiocarcinoma	2C12.10	Approved	[18]
Infigratinib	DMNKBEC	Cholangiocarcinoma	2C12.10	Approved	[19]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[8]
Sulfatinib	DMPOTM4	Neuroendocrine cancer	2B72.1	Phase 3	[9]
ARQ-087	DM02BVQ	Intrahepatic cholangiocarcinoma	2C12.10	Phase 3	[20]
AZD4547	DM3827C	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[21]
Debio 1347	DMZW50O	Solid tumour/cancer	2A00-2F9Z	Phase 2	[22]
AM-001	DMGVQI8	Actinic keratosis	EK90.0	Phase 2	[23]

Drug(s) Targeting Platelet-derived growth factor receptor alpha (PDGFRA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[24]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[25]
Olaratumab	DMNYOIX	Soft tissue sarcoma	2B57	Approved	[26]
Avapritinib	DMK2GZX	Gastrointestinal stromal tumour	2B5B	Approved	[27]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[8]
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[28]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[14]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[29]
MP470	DMELUAK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[30]
MEDI-575	DMI9WVM	Glioblastoma multiforme	2A00.0	Phase 2	[31]

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	[32]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[33]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[34]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[35]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[35]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[36]
Pexidartinib	DMS2J0Z	Tenosynovial giant cell tumour	2F7B	Approved	[37]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[25]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[14]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[29]

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	[33]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[24]
Becaplermin	DM1R5X4	Diabetic complication	5A2Y	Approved	[38]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[8]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[14]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[29]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[39]
SNN-0031	DM2X3BR	Brain injury	NA07.Z	Phase 1/2	[40]
TAK-593	DMNFZOT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[41]
Pyridine derivative 18	DMBZMYT	N. A.	N. A.	Patented	[42]

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	[43]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[35]
Intedanib	DMSTA36	Colorectal cancer	2B91.Z	Approved	[17]
Midostaurin	DMI6E0R	Acute myeloid leukaemia	2A60	Approved	[32]
Gilteritinib	DMTI0ZO	Acute myeloid leukaemia	2A60	Approved	[44]
Pexidartinib	DMS2J0Z	Tenosynovial giant cell tumour	2F7B	Approved	[37]
Pacritinib	DM1T6ZN	Myelofibrosis	2A20.2	Approved	[43]
Quizartinib	DM8Y4JS	Acute myeloid leukaemia	2A60	Approved	[22]
Lestaurtinib	DMQ2AIJ	Acute myeloid leukaemia	2A60	Approved (orphan drug)	[45]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[14]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[34]
VATALANIB	DMY0UEQ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[46]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[39]
Sirna-027	DMZTQD8	Exudative age-related macular degeneration	9B78.3Z	Phase 1/2	[47]
2-(1H-indazol-3-yl)-1H-benzo[d]imidazole	DM0CSH8	Discovery agent	N.A.	Investigative	[48]
AAL-993	DM35RFH	Discovery agent	N.A.	Investigative	[46]
PMID17935989C25	DML8ZBR	Discovery agent	N.A.	Investigative	[49]
2-(5-Phenyl-oxazol-2-ylamino)-benzonitrile	DMX6QMT	Discovery agent	N.A.	Investigative	[15]
4-Chloro-N-(3-chloro-benzoyl)-benzenesulfonamide	DMI3OR9	Discovery agent	N.A.	Investigative	[50]
(2-Methoxy-phenyl)-(5-phenyl-oxazol-2-yl)-amine	DMQWD75	Discovery agent	N.A.	Investigative	[15]

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	[33]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[16]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[35]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[51]
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[52]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[32]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[36]
Fruquintinib	DMHOSCQ	Colorectal cancer	2B91.Z	Approved	[6]
Cabozantinib	DMIYDT4	Medullary thyroid gland carcinoma		Approved	[53]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[7]

Drug(s) Targeting Proto-oncogene c-Src (SRC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[32]
Bosutinib	DMTI8YE	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[32]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[54]
Herbimycin A	DM6YWBF	Solid tumour/cancer	2A00-2F9Z	Approved	[55]
AL3818	DM3WP0N	Alveolar soft part sarcoma	2A60-2C35	Phase 3	[22]
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[22]
Masitinib	DMRSNEU	Amyotrophic lateral sclerosis	8B60.0	Phase 3	[56]
KX-01	DMF0NA9	Actinic keratosis	EK90.0	Phase 3	[57]
Saracatinib	DMBLHGP	Hematologic tumour	2B33.Y	Phase 2	[58]
TPX-0046	DMIVE67	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[59]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fibroblast growth factor receptor 1 (FGFR1)	TTRLW2X	FGFR1_HUMAN	Inhibitor	[1]
Fms-like tyrosine kinase 3 (FLT-3)	TTGJCWZ	FLT3_HUMAN	Inhibitor	[1]
MEK kinase kinase 3 (MAP4K3)	TTI0AHJ	M4K3_HUMAN	Inhibitor	[1]
Platelet-derived growth factor receptor alpha (PDGFRA)	TT8FYO9	PGFRA_HUMAN	Inhibitor	[1]
Platelet-derived growth factor receptor beta (PDGFRB)	TTI7421	PGFRB_HUMAN	Inhibitor	[1]
Proto-oncogene c-Src (SRC)	TT6PKBN	SRC_HUMAN	Inhibitor	[1]
Ribosomal protein S6 kinase alpha-3 (RSK3)	TTUM2ZR	KS6A3_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]
Vascular endothelial growth factor receptor 3 (FLT-4)	TTDCBX5	VGFR3_HUMAN	Inhibitor	[1]
VEGFR1 messenger RNA (VEGFR1 mRNA)	TT1VAUK	VGFR1_HUMAN	Inhibitor	[1]

References

• [1] The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett. 2012 Aug 1;22(15):4979-85.
• [2] Ribosomal S6 kinase (RSK) modulators: a patent review.Expert Opin Ther Pat. 2016 Sep;26(9):1061-78.
• [3] BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo. Biochem J. 2007 Jan 1;401(1):29-38.
• [4] Discovery of an orally efficacious inhibitor of anaplastic lymphoma kinase. J Med Chem. 2012 May 24;55(10):4580-93.
• [5] Indole RSK inhibitors. Part 2: optimization of cell potency and kinase selectivity. Bioorg Med Chem Lett. 2012 Jan 1;22(1):738-42.
• [6] 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.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
• [8] 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.
• [9] Clinical pipeline report, company report or official report of Hutchison Medi Pharma.
• [10] Company report (Medigen)
• [11] Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
• [12] Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol Cancer Ther. 2006 Apr;5(4):995-1006.
• [13] 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).
• [14] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [15] 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.
• [16] Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
• [17] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [18] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [19] Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets. J Bone Miner Res. 2013 Apr;28(4):899-911.
• [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: 1808).
• [21] AZD4547: an orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. Cancer Res. 2012 Apr 15;72(8):2045-56.
• [22] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [23] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029917)
• [24] 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.
• [25] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [26] A phase I study of olaratumab, an anti-platelet-derived growth factor receptor alpha (PDGFRalpha) monoclonal antibody, in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Mar;73(3):595-604.
• [27] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [28] The FLT3 and PDGFR inhibitor crenolanib is a substrate of the multidrug resistance protein ABCB1 but does not inhibit transport function at pharmacologically relevant concentrations.Invest New Drugs.2015 Apr;33(2):300-9.
• [29] National Cancer Institute Drug Dictionary (drug id 452042).
• [30] 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.
• [31] Clinical pipeline report, company report or official report of MedImmune (2011).
• [32] 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.
• [33] 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.
• [34] 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.
• [35] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [36] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [37] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [38] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [39] MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
• [40] Company report (Neuronova)
• [41] 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.
• [42] RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99.
• [43] 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).
• [44] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [45] 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.
• [46] 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.
• [47] 2011 Pipeline of Sirna Therapeutics.
• [48] 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.
• [49] 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.
• [50] 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.
• [51] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [52] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [53] Clinical pipeline report, company report or official report of Exelixis (2011).
• [54] Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles. J Med Chem. 2006 Dec 28;49(26):7868-76.
• [55] In vivo antitumor activity of herbimycin A, a tyrosine kinase inhibitor, targeted against BCR/ABL oncoprotein in mice bearing BCR/ABL-transfected cells. Leuk Res. 1994 Nov;18(11):867-73.
• [56] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [57] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [58] Novel dual Src/Abl inhibitors for hematologic and solid malignancies.Expert Opin Investig Drugs.2010 Aug;19(8):931-45.
• [59] Clinical pipeline report, company report or official report of Turning Point Therapeutics.