Details of the Drug

General Information of Drug (ID: DM3U9BY)

Drug Name

RO-5126766

Synonyms

VS-6766; CH-5126766; Dual Raf/MEK protein kinase inhibitor (cancer), Roche

Indication

Disease Entry	ICD 11	Status	REF
Non-small cell lung cancer	2C25	Phase 2	[1]
Ovarian cancer	2C73	Phase 2	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

471.5

Topological Polar Surface Area (xlogp)

2

Rotatable Bond Count (rotbonds)

7

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

11

Chemical Identifiers

Formula: C21H18FN5O5S
IUPAC Name: 3-[[3-fluoro-2-(methylsulfamoylamino)pyridin-4-yl]methyl]-4-methyl-7-pyrimidin-2-yloxychromen-2-one
Canonical SMILES: CC1=C(C(=O)OC2=C1C=CC(=C2)OC3=NC=CC=N3)CC4=C(C(=NC=C4)NS(=O)(=O)NC)F
InChI: InChI=1S/C21H18FN5O5S/c1-12-15-5-4-14(31-21-25-7-3-8-26-21)11-17(15)32-20(28)16(12)10-13-6-9-24-19(18(13)22)27-33(29,30)23-2/h3-9,11,23H,10H2,1-2H3,(H,24,27)
InChIKey: LMMJFBMMJUMSJS-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 16719221
ChEBI ID: CHEBI:78825
CAS Number: 946128-88-7
TTD ID: D0M6BD

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
MAPK/ERK kinase kinase (MAP3K)	TTROQ37	NOUNIPROTAC	Modulator	[3]
Serine/threonine-protein kinase Raf (RAF)	TTQ9K3Y	ARAF_HUMAN; BRAF_HUMAN; RAF1_HUMAN	Modulator	[3]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

References

1	ClinicalTrials.gov (NCT04625270) A Study of VS-6766 v. VS-6766 + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer With and Without a KRAS Mutation. U.S. National Institutes of Health.
2	ClinicalTrials.gov (NCT02407509) Phase I Trial of RO5126766. U.S. National Institutes of Health.
3	The dual RAF/MEK inhibitor CH5126766/RO5126766 may be a potential therapy for RAS-mutated tumor cells.PLoS One.2014 Nov 25;9(11):e113217.
4	MEK and the inhibitors: from bench to bedside. J Hematol Oncol. 2013; 6: 27.
5	Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
6	RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer.Cancer Res.2009 Sep 1;69(17):6839-47.
7	Intrinsic resistance to selumetinib, a selective inhibitor of MEK1/2, by cAMP-dependent protein kinase A activation in human lung and colorectal cancer cells.Br J Cancer.2012 May 8;106(10):1648-59.
8	Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells. Int J Cancer. 2013 Nov;133(9):2089-101.
9	E6201, a novel kinase inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-1 and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase-1: in vivo effects on cutaneous inflammatory responses by topical administration. J Pharmacol Exp Ther. 2010 Oct;335(1):23-31.
10	Clinical pipeline report, company report or official report of Roche.
11	doi: 10.1158/1535-7163.TARG-13-B281
12	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
13	Company report (eli lily)