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

General Information of Drug (ID: DMELUAK)

• Drug Name: MP470 Drug Info
• Synonyms: Amuvatinib; 850879-09-3; MP-470; MP470; MP 470; Amuvatinib (MP-470); HPK56; UNII-SO9S6QZB4R; Amuvatinib(MP470); N-(benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide; SO9S6QZB4R; HPK-56; HPK 56; N-(Benzo[d][1,3]dioxol-5-ylmethyl)-4-(benzofuro-[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide; N-(1,3-benzodioxol-5-ylmethyl)-4-([1]benzofuro[3,2-d]pyrimidin-4-yl)piperazine-1-carbothioamide; Amuvatinib [USAN:INN]; Amuvatinib (MP-470, HPK 56); PubChem22479; Amuvatinib (USAN/INN)

Indication

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

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 11282283
  ChEBI ID: CHEBI:91389
  CAS Number: CAS 850879-09-3
  TTD Drug ID: DMELUAK

Molecule-Related Drug Atlas

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	[4]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[5]
Olaratumab	DMNYOIX	Soft tissue sarcoma	2B57	Approved	[6]
Avapritinib	DMK2GZX	Gastrointestinal stromal tumour	2B5B	Approved	[7]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[8]
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[9]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[10]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[11]
MEDI-575	DMI9WVM	Glioblastoma multiforme	2A00.0	Phase 2	[12]
Pyridine derivative 18	DMBZMYT	N. A.	N. A.	Patented	[13]

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	[14]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[15]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[16]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[17]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[17]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[18]
Pexidartinib	DMS2J0Z	Tenosynovial giant cell tumour	2F7B	Approved	[19]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[5]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[10]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[11]

Drug(s) Affected By Tyrosine-protein kinase receptor UFO (AXL)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Selenium	DM25CGV	N. A.	N. A.	Approved	[20]
Dactinomycin	DM2YGNW	Adult kidney Wilms tumor		Approved	[21]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[22]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[23]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[21]
Plicamycin	DM7C8YV	Hypercalcaemia	5B91.0	Approved	[24]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[25]
Clodronate	DM9Y6X7	Hypercalcaemia	5B91.0	Approved	[26]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[26]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[26]

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	Modulator	[2]
Tyrosine-protein kinase Kit (KIT)	TTX41N9	KIT_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Gene/Protein Processing	[3]

References

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• [2] 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.
• [3] Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat Genet. 2012 Jul 1;44(8):852-60. doi: 10.1038/ng.2330.
• [4] 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.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [6] 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.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [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] 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.
• [10] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [11] National Cancer Institute Drug Dictionary (drug id 452042).
• [12] Clinical pipeline report, company report or official report of MedImmune (2011).
• [13] RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [18] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [19] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [20] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [21] Genomic profiling uncovers a molecular pattern for toxicological characterization of mutagens and promutagens in vitro. Toxicol Sci. 2011 Jul;122(1):185-97.
• [22] Simvastatin inactivates beta1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells. Cancer Sci. 2007 Jun;98(6):890-9.
• [23] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [24] The human receptor tyrosine kinase Axl gene--promoter characterization and regulation of constitutive expression by Sp1, Sp3 and CpG methylation. Biosci Rep. 2008 Jun;28(3):161-76. doi: 10.1042/BSR20080046.
• [25] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [26] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.