Details of the Drug

General Information of Drug (ID: DMV6GX7)

Drug Name

ONO-7475

Synonyms

1646839-59-9; UNII-0VCB95RHRV; N-(5-((6,7-Dimethoxyquinolin-4-yl)oxy)pyridin-2-yl)-2,5-dioxo-1-phenyl-1,2,5,6,7,8-hexahydroquinoline-3-carboxamide; N-[5-[(6,7-Dimethoxy-4-quinolinyl)oxy]-2-pyridinyl]-1,2,5,6,7,8-hexahydro-2,5-dioxo-1-phenyl-3-quinolinecarboxamide; SCHEMBL16426362; ONO7475; BCP33232; MFCD32689448; s8933; ONO-7475; ONO 7475; HY-114358; CS-0083699; 3-Quinolinecarboxamide, N-(5-((6,7-dimethoxy-4-quinolinyl)oxy)-2-pyridinyl)-1,2,5,6,7,8-hexahydro-2,5-dioxo-1-phenyl-; N-[5-(6,7-dimethoxyquinolin-4-yl)oxypyridin-2-yl]-2,5-dioxo-1-phenyl-7,8-dihydro-6H-quinoline-3-carboxamide

Indication

Disease Entry	ICD 11	Status	REF
Acute leukaemia	2A60	Phase 1/2	[1]
Myelodysplastic syndrome	2A37	Phase 1/2	[1]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

562.6

Topological Polar Surface Area (xlogp)

3.8

Rotatable Bond Count (rotbonds)

7

Hydrogen Bond Donor Count (hbonddonor)

1

Hydrogen Bond Acceptor Count (hbondacc)

8

Chemical Identifiers

Formula: C32H26N4O6
IUPAC Name: N-[5-(6,7-dimethoxyquinolin-4-yl)oxypyridin-2-yl]-2,5-dioxo-1-phenyl-7,8-dihydro-6H-quinoline-3-carboxamide
Canonical SMILES: COC1=CC2=C(C=CN=C2C=C1OC)OC3=CN=C(C=C3)NC(=O)C4=CC5=C(CCCC5=O)N(C4=O)C6=CC=CC=C6
InChI: InChI=1S/C32H26N4O6/c1-40-28-16-21-24(17-29(28)41-2)33-14-13-27(21)42-20-11-12-30(34-18-20)35-31(38)23-15-22-25(9-6-10-26(22)37)36(32(23)39)19-7-4-3-5-8-19/h3-5,7-8,11-18H,6,9-10H2,1-2H3,(H,34,35,38)
InChIKey: WHMMKPWGWNYYFE-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 90645873
CAS Number: 1646839-59-9
TTD ID: DA1MG8

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Tyrosine-protein kinase Mer (MERTK)	TTO7LKR	MERTK_HUMAN	Inhibitor	[2]
Tyrosine-protein kinase UFO (AXL)	TTZPY6J	UFO_HUMAN	Inhibitor	[2]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Acute leukaemia

ICD Disease Classification

2A60

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Tyrosine-protein kinase Mer (MERTK)	DTT	MERTK	5.86E-04	0.3	0.47

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	ClinicalTrials.gov (NCT03176277) A Study of ONO-7475 in Patients With Acute Leukemias. U.S. National Institutes of Health.
2	Clinical pipeline report, company report or official report of Ono Pharmaceutical.
3	MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
4	National Cancer Institute Drug Dictionary (drug name RXDX106).
5	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6	The MERTK/FLT3 inhibitor MRX-2843 overcomes resistance-conferring FLT3 mutations in acute myeloid leukemia. JCI Insight. 2016 Mar;1(3):e85630.
7	National Cancer Institute Drug Dictionary (drug name PF-07265807).
8	A Potent and Selective Dual Inhibitor of AXL and MERTK Possesses Both Immunomodulatory and Tumor-Targeted Activity. Front Oncol. 2020 Dec 7;10:598477.
9	The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature. 2014 Mar 27;507(7493):508-12.
10	G-749, a novel FLT3 kinase inhibitor, can overcome drug resistance for the treatment of acute myeloid leukemia. Blood. 2014 Apr 3;123(14):2209-19.
11	MerTK as a therapeutic target in glioblastoma. Neuro Oncol. 2018 Jan 10;20(1):92-102.
12	UNC569, a novel small-molecule mer inhibitor with efficacy against acute lymphoblastic leukemia in vitro and in vivo. Mol Cancer Ther. 2013 Nov;12(11):2367-77.
13	Company report (Mirati Therapeutics: formerly MethylGene)
14	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
15	AXL Targeting Abrogates Autophagic Flux and Induces Immunogenic Cell Death in Drug-Resistant Cancer Cells. J Thorac Oncol. 2020 Jun;15(6):973-999.
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: 1835).
17	Enapotamab vedotin, an AXL-specific antibody-drug conjugate, shows preclinical antitumor activity in non-small cell lung cancer. JCI Insight. 2019 Nov 1;4(21):e128199.
18	First-in-human phase I study of BPI-9016M, a dual MET/Axl inhibitor, in patients with non-small cell lung cancer. J Hematol Oncol. 2020 Jan 16;13(1):6.