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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

SMILES

CNS(=O)(=O)NC1=C(F)C(CC2=C(C)C3=C(OC2=O)C=C(OC4=NC=CC=N4)C=C3)=CC=N1

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

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
 0.16 µM [IC50]
Inhibitor
8504
 0.056 µM [IC50]
Inhibitor
8504
 0.019 µM [IC50]
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
58.4 ng/mL
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
0.8 mg single, oral
dose: 0.8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
77.7 ng/mL
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
1.2 mg single, oral
dose: 1.2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
128 ng/mL
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
1.8 mg single, oral
dose: 1.8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
171 ng/mL
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
2.25 mg single, oral
dose: 2.25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
148 ng/mL
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
0.8 mg 1 times / day multiple, oral
dose: 0.8 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
355 ng/mL
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
1.2 mg 1 times / day multiple, oral
dose: 1.2 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
430 ng/mL
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
1.8 mg 1 times / day multiple, oral
dose: 1.8 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
618 ng/mL
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
2.25 mg 1 times / day multiple, oral
dose: 2.25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2610 ng × h/mL
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
0.8 mg single, oral
dose: 0.8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
7940 ng × h/mL
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
1.2 mg single, oral
dose: 1.2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
8490 ng × h/mL
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
1.8 mg single, oral
dose: 1.8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
9970 ng × h/mL
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
2.25 mg single, oral
dose: 2.25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
10400 ng × h/mL
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
0.8 mg 1 times / day multiple, oral
dose: 0.8 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
33400 ng × h/mL
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
1.2 mg 1 times / day multiple, oral
dose: 1.2 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
25700 ng × h/mL
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
1.8 mg 1 times / day multiple, oral
dose: 1.8 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
37000 ng × h/mL
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
2.25 mg 1 times / day multiple, oral
dose: 2.25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
47.6 h
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
0.8 mg single, oral
dose: 0.8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
93.7 h
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
1.2 mg single, oral
dose: 1.2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
59.9 h
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
1.8 mg single, oral
dose: 1.8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
62.4 h
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
2.25 mg single, oral
dose: 2.25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
68.5 h
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
0.8 mg 1 times / day multiple, oral
dose: 0.8 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
86.4 h
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
1.2 mg 1 times / day multiple, oral
dose: 1.2 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
52.7 h
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
1.8 mg 1 times / day multiple, oral
dose: 1.8 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
45.8 h
CLINICAL TRIAL
https://pubmed.ncbi.nlm.nih.gov/23860959/
2.25 mg 1 times / day multiple, oral
dose: 2.25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RO5126766 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
PubMed

PubMed

TitleDatePubMed
MEK and the inhibitors: from bench to bedside.
2013-04-12
Patents

Patents

20100004233
2
20110009398
2
20110092700
2
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:29:38 GMT 2025
Edited
by admin
on Mon Mar 31 18:29:38 GMT 2025
Record UNII
D0D4252V97
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
Sulfamide, N-[3-fluoro-4-[[4-methyl-2-oxo-7-(2-pyrimidinyloxy)-2H-1-benzopyran-3-yl]methyl]-2-pyridinyl]-N?-methyl-
Preferred Name English
Avutometinib
USAN   INN  
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
RO-5126766
Code English
RG-7304
Code English
CH-5126766
Code English
CH5126766
Code English
RO5126766
Code English
AVUTOMETINIB [USAN]
Common Name English
Code System Code Type Description
DRUG BANK
DB15254
Created by admin on Mon Mar 31 18:29:38 GMT 2025 , Edited by admin on Mon Mar 31 18:29:38 GMT 2025
PRIMARY
USAN
LM-17
Created by admin on Mon Mar 31 18:29:38 GMT 2025 , Edited by admin on Mon Mar 31 18:29:38 GMT 2025
PRIMARY
PUBCHEM
16719221
Created by admin on Mon Mar 31 18:29:38 GMT 2025 , Edited by admin on Mon Mar 31 18:29:38 GMT 2025
PRIMARY
ChEMBL
CHEMBL3545081
Created by admin on Mon Mar 31 18:29:38 GMT 2025 , Edited by admin on Mon Mar 31 18:29:38 GMT 2025
PRIMARY
FDA UNII
D0D4252V97
Created by admin on Mon Mar 31 18:29:38 GMT 2025 , Edited by admin on Mon Mar 31 18:29:38 GMT 2025
PRIMARY
CAS
946128-88-7
Created by admin on Mon Mar 31 18:29:38 GMT 2025 , Edited by admin on Mon Mar 31 18:29:38 GMT 2025
PRIMARY
NCI_THESAURUS
C80060
Created by admin on Mon Mar 31 18:29:38 GMT 2025 , Edited by admin on Mon Mar 31 18:29:38 GMT 2025
PRIMARY
MANUFACTURER PRODUCT INFORMATION
RO-5126766 FREE BASE
Created by admin on Mon Mar 31 18:29:38 GMT 2025 , Edited by admin on Mon Mar 31 18:29:38 GMT 2025
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 Mon Mar 31 18:29:38 GMT 2025 , Edited by admin on Mon Mar 31 18:29:38 GMT 2025
PRIMARY
INN
11815
Created by admin on Mon Mar 31 18:29:38 GMT 2025 , Edited by admin on Mon Mar 31 18:29:38 GMT 2025
PRIMARY
Related Record Type Details
SERINE/THREONINE-PROTEIN KINASE B-RAF
TARGET -> INHIBITOR
IC50
DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 1
TARGET -> INHIBITOR
Causes MEK to adopt a conformation in which it cannot be phosphorylated by and released from RAF.
IC50
SERINE/THREONINE-PROTEIN KINASE B-RAF V600E
TARGET -> INHIBITOR
IC50
RAF PROTO-ONCOGENE SERINE/THREONINE-PROTEIN KINASE
TARGET -> INHIBITOR
IC50
Related Record Type Details
Structure of Avutometinib
ACTIVE MOIETY
RO-5126766 RG-7304 CH-5126766 CKI-27 R-7304 CAS No. 946128-88-7
NIH
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