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

General Information of Drug (ID: DM6NVTR)

• Drug Name: RXDX-106 Drug Info
• 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]

• Cross-matching ID:
  PubChem CID: 71576419
  CAS Number: CAS 1437321-24-8
  TTD Drug ID: DM6NVTR

Molecule-Related Drug Atlas

Drug(s) Targeting Proto-oncogene c-Met (MET)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[3]
Cabozantinib	DMIYDT4	Medullary thyroid gland carcinoma		Approved	[4]
Amivantamab	DMZ7AMY	Non-small-cell lung cancer	2C25	Approved	[5]
Capmatinib	DMYCXKL	Non-small-cell lung cancer	2C25.Y	Approved	[6]
Tepotinib	DMUQ0E8	Non-small-cell lung cancer	2C25	Approved	[7]
RG3638	DMTQJE0	Gastric adenocarcinoma	2B72	Phase 3	[8]
Savolitinib	DMALFKX	Renal cell carcinoma	2C90	Phase 3	[9]
Beperminogene perplasmid	DM6RWBN	Critical limb ischemia	BD4Y	Phase 3	[10]
Tivantinib	DMNVP8Q	Hepatocellular carcinoma	2C12.02	Phase 3	[11]
MGCD516	DM752PU	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[8]

Drug(s) Targeting Tyrosine-protein kinase Mer (MERTK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[12]
ONO-7475	DMV6GX7	Acute leukaemia	2A60	Phase 1/2	[9]
ONO-7475	DMV6GX7	Acute leukaemia	2A60	Phase 1/2	[13]
MRX-2843	DMM5N8P	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]
PF-07265807	DMSMNRQ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[15]
INCB81776	DMFOXGB	Solid tumour/cancer	2A00-2F9Z	Phase 1	[16]
LDC1267	DMH7R6L	Discovery agent	N.A.	Investigative	[17]
G749	DMC7HIS	Discovery agent	N.A.	Investigative	[18]
UNC2025	DMCU59W	Glioblastoma of brain	2A00.00	Investigative	[19]
UNC569	DMJL6ZM	Acute lymphoblastic leukaemia	2A85	Investigative	[20]

Drug(s) Targeting Tyrosine-protein kinase UFO (AXL)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Gilteritinib	DMTI0ZO	Acute myeloid leukaemia	2A60	Approved	[9]
MGCD265	DMRPCF2	Non-small-cell lung cancer	2C25.Y	Phase 2	[21]
BI-505	DMSZQHX	Multiple myeloma	2A83	Phase 2	[22]
Bemcentinib	DM0YCPL	Myelodysplastic syndrome	2A37	Phase 2	[23]
BGB-324	DMDI43Y	Breast cancer	2C60-2C65	Phase 2	[24]
Mecbotamab vedotin	DMU5KH4	Ovarian cancer	2C73	Phase 2	[25]
ONO-7475	DMV6GX7	Acute leukaemia	2A60	Phase 1/2	[9]
ONO-7475	DMV6GX7	Acute leukaemia	2A60	Phase 1/2	[13]
TP-0903	DMHTG8P	Chronic lymphocytic leukaemia	2A82.0	Phase 1/2	[9]
Enapotamab vedotin	DM1PQJO	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[26]

Drug(s) Targeting TYRO3 tyrosine kinase receptor (TYRO3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BDBM50444058	DM9GLQB	N. A.	N. A.	Patented	[27]
BDBM50444062	DMR2UGC	N. A.	N. A.	Patented	[27]
KRDULPYOVRWKMA-UHFFFAOYSA-N	DMRY7KV	N. A.	N. A.	Patented	[28]
BDBM50444059	DMS0EMU	N. A.	N. A.	Patented	[27]
US10053465, 8	DM42XWO	N. A.	N. A.	Patented	[28]
US10053465, 12	DMPM8VB	N. A.	N. A.	Patented	[29]
US10053465, 5	DMV7BF2	N. A.	N. A.	Patented	[29]
LDC1267	DMH7R6L	Discovery agent	N.A.	Investigative	[17]

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]

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] 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.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [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] Clinical pipeline report, company report or official report of BioAtla
• [26] 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.
• [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.