Avutometinib

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NCATS

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H18FN5O5S
Molecular Weight	471.462
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of Avutometinib

Structure Search

SMILES

CNS(=O)(=O)NC1=NC=CC(CC2=C(C)C3=CC=C(OC4=NC=CC=N4)C=C3OC2=O)=C1F

InChI

InChIKey=LMMJFBMMJUMSJS-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C21H18FN5O5S
Molecular Weight	471.462
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Approval Year

Targets

Targets

Primary Target	Pharmacology	Condition	Potency
Dual specificity mitogen-activated protein kinase kinase 1 20 Target ID: CHEMBL3587 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23667175	Inhibitor 8297		0.16 µM [IC50]
Serine/threonine-protein kinase RAF 10 Target ID: CHEMBL1906 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23667175	Inhibitor 8297		0.056 µM [IC50]
Serine/threonine-protein kinase B-raf 20 Target ID: CHEMBL5145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23667175	Inhibitor 8297		0.019 µM [IC50]

PubMed

PubMed

Title	Date	PubMed
MEK and the inhibitors: from bench to bedside.	2013 Apr 12	23587417

Patents

Patents

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:29:59 UTC 2023` Edited by `admin` on `Fri Dec 15 16:29:59 UTC 2023`
Record UNII	D0D4252V97
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

Avutometinib

Official Name

English

R-7304

Code

English

N-[3-fluoro-4-({4-methyl-2-oxo-7-[(pyrimidin-2-yl)oxy]-2H-1-benzopyran-3-yl}methyl)pyridin-2-yl]-N′-methylsulfuric diamide

Systematic Name

English

CKI-27

Code

English

Avutometinib [WHO-DD]

Common Name

English

avutometinib [INN]

Common Name

English

VS-6766

Code

English

Sulfamide, N-[3-fluoro-4-[[4-methyl-2-oxo-7-(2-pyrimidinyloxy)-2H-1-benzopyran-3-yl]methyl]-2-pyridinyl]-N′-methyl-

Systematic Name

English

RO-5126766

Code

English

RG-7304

Code

English

CH-5126766

Code

English

CH5126766

Code

English

AVUTOMETINIB [USAN]

Common Name

English

RO-5126766 FREE BASE

Code

English

Code System Code Type Description

DRUG BANK

DB15254

Created by admin on Fri Dec 15 16:29:59 UTC 2023 , Edited by admin on Fri Dec 15 16:29:59 UTC 2023

PRIMARY

USAN

LM-17

Created by admin on Fri Dec 15 16:29:59 UTC 2023 , Edited by admin on Fri Dec 15 16:29:59 UTC 2023

PRIMARY

PUBCHEM

16719221

Created by admin on Fri Dec 15 16:29:59 UTC 2023 , Edited by admin on Fri Dec 15 16:29:59 UTC 2023

PRIMARY

ChEMBL

CHEMBL3545081

Created by admin on Fri Dec 15 16:29:59 UTC 2023 , Edited by admin on Fri Dec 15 16:29:59 UTC 2023

PRIMARY

FDA UNII

D0D4252V97

Created by admin on Fri Dec 15 16:29:59 UTC 2023 , Edited by admin on Fri Dec 15 16:29:59 UTC 2023

PRIMARY

CAS

946128-88-7

Created by admin on Fri Dec 15 16:29:59 UTC 2023 , Edited by admin on Fri Dec 15 16:29:59 UTC 2023

PRIMARY

NCI_THESAURUS

C80060

Created by admin on Fri Dec 15 16:29:59 UTC 2023 , Edited by admin on Fri Dec 15 16:29:59 UTC 2023

PRIMARY

MANUFACTURER PRODUCT INFORMATION

RO-5126766 FREE BASE

Created by admin on Fri Dec 15 16:29:59 UTC 2023 , Edited by admin on Fri Dec 15 16:29:59 UTC 2023

PRIMARY

In vitro: In HCT116 KRAS-mutant colorectal cancer cells, CH5126766 significantly reduces the levels of phospho-MEK and phospho-ERK. CH5126766 inhibits RAF kinase by binding to MEK1, and causes MEK to become a dominant negative inhibitor of RAF. In Raf or RAS-mutant cell lines SK-MEL-28, SK-MEL-2, MIAPaCa-2, SW480, HCT116, and PC3 cells, CH5126766 inhibits cell growth with IC50 of 65, 28, 40, 46, and 277 nM, respectively. In two melanoma cell lines with the BRAF V600E or NRAS mutation, RO5126766 induces G1 cell cycle arrest accompanied by up-regulation of the CDK inhibitor p27 and down-regulation of cyclinD1. In vivo: In an HCT116 (G13D KRAS) mouse xenograft model, CH5126766 (25 mg/kg, p.o.) inhibits ERK signaling output more effectively than a standard MEK inhibitor that induces MEK phosphorylation and has potent antitumor activity. In the HCT116 (K-ras) and COLO205 (B-raf) mutant xenografts, CH5126766 (0.3 mg/kg) causes significant decreases in (18F)FDG uptake. In the SK-MEL-2 xenograft model, RO5126766 also suppresses the tumor growth.

SMS_ID

300000027351

Created by admin on Fri Dec 15 16:29:59 UTC 2023 , Edited by admin on Fri Dec 15 16:29:59 UTC 2023

PRIMARY

INN

11815

Created by admin on Fri Dec 15 16:29:59 UTC 2023 , Edited by admin on Fri Dec 15 16:29:59 UTC 2023

PRIMARY

Related Record Type Details


					S54X4ZF5K5

SERINE/THREONINE-PROTEIN KINASE B-RAF

TARGET -> INHIBITOR

Qualification:

IC50

Amount:


					CTZ3P20I6M

DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 1

TARGET -> INHIBITOR

Comments:

Causes MEK to adopt a conformation in which it cannot be phosphorylated by and released from RAF.

Qualification:

IC50

Amount:


					U7FKT8J0J3

SERINE/THREONINE-PROTEIN KINASE B-RAF V600E

TARGET -> INHIBITOR

Qualification:

IC50

Amount:


					5XY6H1L8TA

RAF PROTO-ONCOGENE SERINE/THREONINE-PROTEIN KINASE

TARGET -> INHIBITOR

Qualification:

IC50

Amount:

Related Record Type Details


					D0D4252V97

ACTIVE MOIETY

Comments:

RO-5126766 RG-7304 CH-5126766 CKI-27 R-7304 CAS No. 946128-88-7

Amount: