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

General Information of Drug (ID: DMMHX9K)

• Drug Name: XL-820 Drug Info
• Synonyms: EXEL-9820

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 2	[1]

• Cross-matching ID: TTD Drug ID: DMMHX9K

Molecule-Related Drug Atlas

Drug(s) Targeting Vascular endothelial growth factor receptor (VEGFR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Intedanib	DMSTA36	Colorectal cancer	2B91.Z	Approved	[3]
Fruquintinib	DMHOSCQ	Colorectal cancer	2B91.Z	Approved	[4]
Sulfatinib	DMPOTM4	Neuroendocrine cancer	2B72.1	Phase 3	[4]
KH-902	DM8VO16	Diabetic macular edema	9B71.02	Phase 3	[5]
ABP 938	DM00ACQ	Neovascular age-related macular degeneration	9B78.3Z	Phase 3	[6]
BAY-57-9352	DMVA5NS	Gastric adenocarcinoma	2B72	Phase 2	[7]
X-82	DMW1NKO	Age-related macular degeneration	9B75.0	Phase 2	[4]
Vorolanib	DMIM1U9	Non-small-cell lung cancer	2C25	Phase 2	[8]
BFH-772	DMVUX1C	Psoriasis vulgaris	EA90	Phase 2	[9]
ASP-8477	DMBZQS7	Neuropathic pain	8E43.0	Phase 2	[10]

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	[11]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[12]
Olaratumab	DMNYOIX	Soft tissue sarcoma	2B57	Approved	[13]
Avapritinib	DMK2GZX	Gastrointestinal stromal tumour	2B5B	Approved	[14]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[15]
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[16]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[17]
MP470	DMELUAK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[18]
MEDI-575	DMI9WVM	Glioblastoma multiforme	2A00.0	Phase 2	[19]
Pyridine derivative 18	DMBZMYT	N. A.	N. A.	Patented	[20]

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	[21]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[22]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[23]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[24]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[24]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[25]
Pexidartinib	DMS2J0Z	Tenosynovial giant cell tumour	2F7B	Approved	[26]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[12]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[17]
MP470	DMELUAK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[18]

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	[22]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[11]
Becaplermin	DM1R5X4	Diabetic complication	5A2Y	Approved	[27]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[15]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[17]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[28]
SNN-0031	DM2X3BR	Brain injury	NA07.Z	Phase 1/2	[29]
TAK-593	DMNFZOT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[30]
Pyridine derivative 18	DMBZMYT	N. A.	N. A.	Patented	[20]
PMID25656651-Compound-21a	DMCKAON	N. A.	N. A.	Patented	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Platelet-derived growth factor receptor alpha (PDGFRA)	TT8FYO9	PGFRA_HUMAN	Inhibitor	[2]
Platelet-derived growth factor receptor beta (PDGFRB)	TTI7421	PGFRB_HUMAN	Inhibitor	[2]
Tyrosine-protein kinase Kit (KIT)	TTX41N9	KIT_HUMAN	Inhibitor	[2]
Vascular endothelial growth factor receptor (VEGFR)	TTVJ1D8	NOUNIPROTAC	Inhibitor	[2]

References

• [1] ClinicalTrials.gov (NCT00570635) A Phase 2 Study of XL820 in Adults With Advanced GIST Resistant to Imatinib and/or Sunitinib. U.S. National Institutes of Health.
• [2] National Cancer Institute Drug Dictionary (drug id 452042).
• [3] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Effects of intravitreal injection of KH902, a vascular endothelial growth factor receptor decoy, on the retinas of streptozotocin-induced diabetic rats. Diabetes Obes Metab. 2012 Jul;14(7):644-53.
• [6] Clinical pipeline report, company report or official report of Amgen
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Vorolanib, an oral VEGFR/PDGFR dual tyrosine kinase inhibitor for treatment of patients with advanced solid tumors: An open-label, phase I dose escalation and dose expansion trial. Chin J Cancer Res. 2021 Feb 28;33(1):103-114.
• [9] CA patent application no. 841416, Method of selecting therapeutic indications.
• [10] ClinicalTrials.gov (NCT02065349) A Study Into Pain Relief Given by ASP8477 for Peripheral Neuropathic Pain (Either Post-herpetic Neuralgia or Painful Diabetic Peripheral Neuropathy) and Its Safety. U.S. National Institutes of Health.
• [11] 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.
• [12] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [13] 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.
• [14] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [15] 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.
• [16] 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.
• [17] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [18] 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.
• [19] Clinical pipeline report, company report or official report of MedImmune (2011).
• [20] RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99.
• [21] 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.
• [22] 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.
• [23] 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.
• [24] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [25] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [26] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [27] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [28] MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
• [29] Company report (Neuronova)
• [30] 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.
• [31] Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.