Compound Detail

CHEMBL3264002

AVUTOMETINIB

🧪 Phase III

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🧪 Phase III

CNS(=O)(=O)Nc1nccc(Cc2c(C)c3ccc(Oc4ncccn4)cc3oc2=O)c1F

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL3264002
Name	AVUTOMETINIB
Phase	Phase III
Structure Type	MOL
InChI Key	LMMJFBMMJUMSJS-UHFFFAOYSA-N

Known Names

Avutometinib CH-5126766 CH5126766 CKI-27 R-7304 Rg-7304 Ro 5126766 Ro-5126766 VS-6766

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

471.5

MW (Da)

2.68

ALogP

HBA

HBD

136.3

PSA (Å²)

0.39

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Achiral

USAN Stem	-tinib
USAN Year	2022

Extended Properties

Molecular Formula	C21H18FN5O5S
MW	471.47
Aromatic Rings	4
Heavy Atoms	33
NP-Likeness	-0.97

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Dual specificity mitogen-activated protein kinase kinase 1 inhibitor	INHIBITOR	Dual specificity mitogen-activated protein kinase kinase 1	✓	✓
Dual specificity mitogen-activated protein kinase kinase 2 inhibitor	INHIBITOR	Dual specificity mitogen-activated protein kinase kinase 2	✓	✓

Indications

Ovarian Neoplasms Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms Colorectal Neoplasms Genital Neoplasms, Female Thyroid Neoplasms Uveal Melanoma Carcinoma, Endometrioid Melanoma Multiple Myeloma Neoplasms Pancreatic Neoplasms Glioblastoma

Activity Summary

IC50 28 meas. best 8.22

Kd 4 meas. best 8.15

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
HL-60 CHEMBL383	IC50	8.22	8.22	6.0	1
Serine/threonine-protein kinase B-raf CHEMBL5145	Kd	8.15	8.15	7.0	1
Serine/threonine-protein kinase B-raf CHEMBL5145	IC50	8.09	7.905	8.2	2
Unchecked CHEMBL612545	IC50	7.77	7.0033	17.0	3
SK-MEL-2 CHEMBL614917	IC50	7.55	7.55	28.0	1
Dual specificity mitogen-activated protein kinase kinase 1 CHEMBL3587	Kd	7.52	7.52	30.0	1
Dual specificity mitogen-activated protein kinase kinase 2 CHEMBL2964	Kd	7.43	7.43	37.0	1
MIA PaCa-2 CHEMBL614725	IC50	7.4	7.17	40.0	2
HCT-116 CHEMBL394	IC50	7.4	6.8425	40.0	4
SW480 CHEMBL612544	IC50	7.34	7.34	46.0	1
C32 CHEMBL1075401	IC50	7.33	7.33	47.0	1
RAF proto-oncogene serine/threonine-protein kinase CHEMBL1906	IC50	7.25	7.25	56.0	2
SK-MEL-28 CHEMBL614919	IC50	7.19	7.19	65.0	1
Dual specificity mitogen-activated protein kinase kinase 1 CHEMBL3587	IC50	6.8	6.8	160.0	3
Dual specificity mitogen-activated protein kinase kinase; MEK1/2 CHEMBL2111289	IC50	6.8	6.8	160.0	1
MDA-MB-231 CHEMBL400	IC50	6.77	6.77	170.0	1
SARS-CoV-2 CHEMBL4303835	IC50	6.22	6.22	600.0	1
A549 CHEMBL392	IC50	5.91	5.91	1240.0	1
Dual specificity mitogen-activated protein kinase kinase 5 CHEMBL4948	Kd	5.7	5.7	1996.0	1
Cytochrome P450 2C9 CHEMBL3397	IC50	4.92	4.57	12000.0	2
L02 CHEMBL4296457	IC50	4.76	4.76	17270.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	1334731.57	ng.hr.mL-1	Mus musculus
CL	0.5	mL.min-1.g-1	Homo sapiens
CL	1.1	mL.min-1.kg-1	Mus musculus
CL	0.7	mL.min-1.kg-1	Rattus norvegicus
CL	0.1	mL.min-1.kg-1	Macaca fascicularis
F	93.0	%	Mus musculus
F	66.0	%	Rattus norvegicus
F	82.0	%	Macaca fascicularis

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
HL-60	IC50	=	6.0	nM	8.22	Antiproliferative activity against human HL60 cells harboring NRAS K61L mutant a...	32305784
Serine/threonine-protein kinase B-raf	Kd	=	7.0	nM	8.15	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Serine/threonine-protein kinase B-raf	IC50	=	8.2	nM	8.09	Inhibition of human BRAF V600E mutant using 5-Fl-SGQLIDSMANSFV-NH2 peptide as su...	35849914
Unchecked	IC50	=	17.0	nM	7.77	Antiproliferative activity against human A375 cells harboring BRAF V600E mutant ...	32305784
Serine/threonine-protein kinase B-raf	IC50	=	19.0	nM	7.72	Inhibition of wild type human BRAF using 5-Fl-SGQLIDSMANSFV-NH2 peptide as subst...	35849914
SK-MEL-2	IC50	=	28.0	nM	7.55	Antiproliferative activity against human SK-MEL-2 cells harboring NRAS Q61R muta...	35849914
Dual specificity mitogen-activated protein kinase kinase 1	Kd	=	30.0	nM	7.52	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Dual specificity mitogen-activated protein kinase kinase 2	Kd	=	37.0	nM	7.43	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
HCT-116	IC50	=	40.0	nM	7.4	Inhibition of human HCT116 cell growth after 96 hrs by counting kit-8 analysis	24900832
MIA PaCa-2	IC50	=	40.0	nM	7.4	Antiproliferative activity against human MIA PaCa-2 cells harboring NRAS G12C mu...	35849914
SW480	IC50	=	46.0	nM	7.34	Antiproliferative activity against human SW480 cells harboring NRAS G12V mutant ...	35849914
C32	IC50	=	47.0	nM	7.33	Growth inhibition of human C32 cells harboring R-Raf V600E mutant	24900832
HCT-116	IC50	=	53.0	nM	7.28	Antiproliferative activity against human HCT116 cells harboring KRAS G13D mutant...	32305784
RAF proto-oncogene serine/threonine-protein kinase	IC50	=	56.0	nM	7.25	Inhibition of truncated active C-Raf (unknown origin) assessed as MEK1 phosphory...	24900832
RAF proto-oncogene serine/threonine-protein kinase	IC50	=	56.0	nM	7.25	Inhibition of human CRAF using 5-Fl-SGQLIDSMANSFV-NH2 peptide as substrate by FR...	35849914
SK-MEL-28	IC50	=	65.0	nM	7.19	Antiproliferative activity against human SK-MEL-28 cells harboring BRAF V600E mu...	35849914
MIA PaCa-2	IC50	=	115.0	nM	6.94	Antiproliferative activity against human MIA PaCa-2 cells harboring KRAS G12C mu...	39166848
Dual specificity mitogen-activated protein kinase kinase 1	IC50	=	160.0	nM	6.8	Inhibition of MEK1 (unknown origin)	34655985
Dual specificity mitogen-activated protein kinase kinase; MEK1/2	IC50	=	160.0	nM	6.8	TBD: TBD	-
Dual specificity mitogen-activated protein kinase kinase 1	IC50	=	160.0	nM	6.8	Inhibition of MEK1 (unknown origin)	38183777

Literature References

PubMed	DOI	Target Context	# Activities
32305784	10.1016/j.ejmech.2020.112271	MDA-MB-231	9
29191878	10.1126/science.aan4368	Unchecked	5
24900832	10.1021/ml400379x	Mus musculus	5
32305784	10.1016/j.ejmech.2020.112271	Dual specificity mitogen-activated protein kinase kinase; MEK1/2	4
25766633	10.1016/j.bmc.2015.02.053	Unchecked	3
25766633	10.1016/j.bmc.2015.02.053	Dual specificity mitogen-activated protein kinase kinase 1	3
24900832	10.1021/ml400379x	C32	3
24900832	10.1021/ml400379x	Cynomolgus monkey	2
-	10.6019/CHEMBL4495565	SARS-CoV-2	2
39166848	10.1021/acs.jmedchem.4c00860	MIA PaCa-2	2
39166848	10.1021/acs.jmedchem.4c00860	HCT-116	2
35849914	10.1016/j.bmc.2022.116922	Unchecked	2
35849914	10.1016/j.bmc.2022.116922	Serine/threonine-protein kinase B-raf	2
39166848	10.1021/acs.jmedchem.4c00860	Dual specificity mitogen-activated protein kinase kinase 1	2
24900832	10.1021/ml400379x	Rattus norvegicus	2
39166848	10.1021/acs.jmedchem.4c00860	Serine/threonine-protein kinase B-raf	2
24900832	10.1021/ml400379x	Cytochrome P450 3A4	2
24900832	10.1021/ml400379x	Cytochrome P450 2C9	2
24900832	10.1021/ml400379x	ADMET	2
-	10.6019/CHEMBL4808148	Histone deacetylase 6	2

Data from ChEMBL 36 via Core Engine