General Information of Drug (ID: DM6NVTR)

Drug Name
RXDX-106
Synonyms
CEP-40783; 1437321-24-8; CEP40783; UNII-1969ZJE05Q; 1969ZJE05Q; N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3-(4-fluorophenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide; N-[4-(6,7-dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]-3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide; RXDX-106 (CEP-40783); SCHEMBL16089863; BCP25839; EX-A2540; MFCD28502441; NSC797770; s8570; AKOS032960472; ZINC205893112; CCG-270157; CS-6371; NSC-797770; SB18930; AC-31425; AS-35141; HY-100946; N-(4-((6,7-Dimethoxy-4-quinolinyl)oxy)-3-fluorophenyl)-3-(4-fluorophenyl)-1,2,3,4-tetrahydro-1-(1-methylethyl)-2,4-dioxo-5-pyrimidinecarboxamide
Indication
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 588.6
Topological Polar Surface Area (xlogp) 4.7
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 9
Chemical Identifiers
Formula
C31H26F2N4O6
IUPAC Name
N-[4-(6,7-dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]-3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide
Canonical SMILES
CC(C)N1C=C(C(=O)N(C1=O)C2=CC=C(C=C2)F)C(=O)NC3=CC(=C(C=C3)OC4=C5C=C(C(=CC5=NC=C4)OC)OC)F
InChI
InChI=1S/C31H26F2N4O6/c1-17(2)36-16-22(30(39)37(31(36)40)20-8-5-18(32)6-9-20)29(38)35-19-7-10-26(23(33)13-19)43-25-11-12-34-24-15-28(42-4)27(41-3)14-21(24)25/h5-17H,1-4H3,(H,35,38)
InChIKey
FKCWHHYUMFGOPY-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
71576419
CAS Number
1437321-24-8
TTD ID
D7HZ3T

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Proto-oncogene c-Met (MET) TTNDSF4 MET_HUMAN Inhibitor [2]
TYRO3 tyrosine kinase receptor (TYRO3) TTIEMFN TYRO3_HUMAN Inhibitor [2]
Tyrosine-protein kinase Mer (MERTK) TTO7LKR MERTK_HUMAN Inhibitor [2]
Tyrosine-protein kinase UFO (AXL) TTZPY6J UFO_HUMAN Inhibitor [2]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Solid tumour/cancer
ICD Disease Classification 2A00-2F9Z
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
Proto-oncogene c-Met (MET) DTT MET 1.08E-03 -0.24 -0.4
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 ClinicalTrials.gov (NCT03454243) Oral Immunomodulatory Tyrosine Kinase Inhibitor in Patients With Locally Advanced or Metastatic Solid Tumors (TITAN). U.S. National Institutes of Health.
2 National Cancer Institute Drug Dictionary (drug name RXDX106).
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 Clinical pipeline report, company report or official report of Exelixis (2011).
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
7 Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC. Cancer Discov. 2020 Aug;10(8):1194-1209.
8 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: 1815).
9 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
10 Beperminogene perplasmid for the treatment of critical limb ischemia. Expert Rev Cardiovasc Ther. 2014 Oct;12(10):1145-56.
11 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. (Ligand id: 7948).
12 MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
13 Clinical pipeline report, company report or official report of Ono Pharmaceutical.
14 The MERTK/FLT3 inhibitor MRX-2843 overcomes resistance-conferring FLT3 mutations in acute myeloid leukemia. JCI Insight. 2016 Mar;1(3):e85630.
15 National Cancer Institute Drug Dictionary (drug name PF-07265807).
16 A Potent and Selective Dual Inhibitor of AXL and MERTK Possesses Both Immunomodulatory and Tumor-Targeted Activity. Front Oncol. 2020 Dec 7;10:598477.
17 The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature. 2014 Mar 27;507(7493):508-12.
18 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.
19 MerTK as a therapeutic target in glioblastoma. Neuro Oncol. 2018 Jan 10;20(1):92-102.
20 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.
21 Company report (Mirati Therapeutics: formerly MethylGene)
22 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
23 AXL Targeting Abrogates Autophagic Flux and Induces Immunogenic Cell Death in Drug-Resistant Cancer Cells. J Thorac Oncol. 2020 Jun;15(6):973-999.
24 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).
25 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.
26 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.
27 Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity. US9649309.
28 Pyrrolopyrimidine derivatives as TAM inhibitors. US10053465.
29 Fused bicyclic 1,2,4-triazine compounds as TAM inhibitors. US9708333.