Compound Detail

CHEMBL1614701

SELUMETINIB

💊 Approved Drug

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💊 Approved Drug

Cn1cnc2c(F)c(Nc3ccc(Br)cc3Cl)c(C(=O)NOCCO)cc21

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL1614701
Name	SELUMETINIB
Phase	Approved
Structure Type	MOL
InChI Key	CYOHGALHFOKKQC-UHFFFAOYSA-N
Therapeutic	✓ Yes

Known Names

ARRY-142886 ARRY-886 Azd-6244 AZD6244 Selumetinib

430

Targets

593

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

457.7

MW (Da)

3.53

ALogP

HBA

HBD

88.4

PSA (Å²)

0.39

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	2020
Availability	Prescription
Chirality	Achiral

Routes of Administration

Oral

Flags

First in Class Chemical Probe

USAN Stem	-tinib
USAN Year	2009

Extended Properties

Molecular Formula	C17H15BrClFN4O3
MW	457.69
Aromatic Rings	3
Heavy Atoms	27
NP-Likeness	-1.23

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

Neoplasms Neoplasms Carcinoma, Non-Small-Cell Lung Thyroid Neoplasms Thyroid Neoplasms Thyroid Neoplasms Uveal Melanoma Uveal Melanoma Adenocarcinoma Adenocarcinoma, Follicular Bile Duct Neoplasms Biliary Tract Neoplasms Breast Neoplasms Breast Neoplasms Carcinoma, Squamous Cell Carcinoma, Squamous Cell Cholangiocarcinoma Colorectal Neoplasms Colorectal Neoplasms Gallbladder Neoplasms

ATC Classification

L01EE04

selumetinib

Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 565 meas. best 8.5

Kd 26 meas. best 7.85

EC50 2 meas. best 6.12

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
CHP-212 CHEMBL1075423	IC50	8.5	8.5	3.2	1
Dual specificity mitogen-activated protein kinase kinase 1 CHEMBL3587	IC50	8.05	6.3062	9.0	13
Dual specificity mitogen-activated protein kinase kinase; MEK1/2 CHEMBL2111289	IC50	7.85	7.85	14.0	2
Unchecked CHEMBL612545	IC50	7.85	7.85	14.0	1
Unchecked CHEMBL612545	Kd	7.85	7.85	14.0	1
SW-620 CHEMBL612262	IC50	7.82	7.17	15.0	2
H9 CHEMBL614806	IC50	7.64	7.64	22.9	1
HL-60 CHEMBL383	IC50	7.61	7.61	24.6	1
A-375 CHEMBL613859	IC50	7.51	7.51	31.0	1
NOMO-1 CHEMBL2366198	IC50	7.5	7.5	32.0	1
HepG2 CHEMBL395	IC50	7.5	7.5	32.0	1
DU-4475 CHEMBL2366246	IC50	7.47	7.47	33.7	1
M14 CHEMBL614317	IC50	7.43	7.43	36.9	1
Dual specificity mitogen-activated protein kinase kinase 1 CHEMBL3587	Kd	7.39	7.0975	41.0	4
Dual specificity mitogen-activated protein kinase kinase 2 CHEMBL2964	Kd	7.28	6.53	52.0	4
Malme-3M CHEMBL614021	IC50	7.23	7.23	59.0	1
COLO 205 CHEMBL614561	IC50	7.23	7.23	59.0	1
ASPC1 CHEMBL612588	IC50	7.19	6.84	64.2	2
NON-PROTEIN TARGET CHEMBL3879801	IC50	7.16	6.3533	69.0	3
HT-144 CHEMBL2366291	IC50	7.05	7.05	89.0	1
SK-N-AS CHEMBL1075578	IC50	7.03	7.03	92.8	1
LB2518-MEL CHEMBL2366335	IC50	7.03	7.03	93.8	1
C32 CHEMBL1075401	IC50	7.01	7.01	98.2	1
BaF3 CHEMBL614524	IC50	7.0	7.0	100.0	1
BHT-101 CHEMBL1075398	IC50	6.97	6.97	106.9	1
KY821 CHEMBL2366190	IC50	6.97	6.97	107.2	1
SK-CO-1 CHEMBL1075576	IC50	6.93	6.93	117.0	1
CP50-MEL-B CHEMBL2366076	IC50	6.89	6.89	127.9	1
MEL-HO CHEMBL1075500	IC50	6.86	6.86	138.8	1
MIA PaCa-2 CHEMBL614725	IC50	6.85	6.45	142.0	2
EOL1 CHEMBL614489	IC50	6.84	6.84	144.8	1
DOK CHEMBL1075435	IC50	6.83	6.83	147.1	1
SH-4 CHEMBL2366309	IC50	6.78	6.78	166.5	1
BPH-1 CHEMBL2366131	IC50	6.74	6.74	182.3	1
HuP-T4 CHEMBL1075478	IC50	6.71	6.71	195.3	1
Structural maintenance of chromosomes protein 2 CHEMBL4105890	Kd	6.68	6.68	209.0	1
HTC-C3 CHEMBL1075472	IC50	6.67	6.67	214.6	1
A549 CHEMBL392	IC50	6.67	6.0633	214.1	3
KU812 cell line CHEMBL613997	IC50	6.67	6.67	211.7	1
A101D CHEMBL2366306	IC50	6.62	6.62	240.3	1
ONS-76 CHEMBL2366068	IC50	6.61	6.61	244.5	1
RKO CHEMBL614879	IC50	6.61	6.61	248.4	1
WM-115 CHEMBL1075611	IC50	6.57	6.57	267.5	1
HCC 2998 CHEMBL613855	IC50	6.57	6.57	269.1	1
C2BBe1 CHEMBL2366283	IC50	6.56	6.56	272.6	1
RVH-421 CHEMBL1075567	IC50	6.55	6.55	279.4	1
H-EMC-SS CHEMBL1075451	IC50	6.54	6.54	291.0	1
ML-2 CHEMBL614356	IC50	6.53	6.53	293.6	1
UACC-257 CHEMBL612796	IC50	6.49	6.49	321.8	1
CAL-39 CHEMBL1075410	IC50	6.48	6.48	332.3	1

Pharmacokinetic Data

Parameter	Value	Units	Species
CL	1.0	mL.min-1.kg-1	Rattus norvegicus
CL	1.0	mL.min-1.kg-1	Rattus norvegicus
F	14.0	%	Rattus norvegicus
F	24.0	%	Rattus norvegicus
T1/2	3.8	hr	Rattus norvegicus
T1/2	4.1	hr	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
CHP-212	IC50	=	3.153	nM	8.5	SANGER: Inhibition of human CHP-212 cell growth in a cell viability assay.	-
Dual specificity mitogen-activated protein kinase kinase 1	IC50	=	9.0	nM	8.05	Inhibition of MEK1 (unknown origin) using Ser/Thr 03 peptide substrate after 4 h...	29317148
Unchecked	Kd	=	14.0	nM	7.85	Binding affinity to MEK1/2 (unknown origin) assessed as dissociation constant	35312319
Dual specificity mitogen-activated protein kinase kinase 1	IC50	=	14.0	nM	7.85	Inhibition of MEK1 in human HeLa-MaTu matched pair cells assessed as reduction i...	26611920
Dual specificity mitogen-activated protein kinase kinase; MEK1/2	IC50	=	14.0	nM	7.85	Inhibition of MEK (unknown origin)	32828424
Unchecked	IC50	=	14.0	nM	7.85	Inhibition of MEK (unknown origin)	33539089
Dual specificity mitogen-activated protein kinase kinase; MEK1/2	IC50	=	14.0	nM	7.85	Inhibition of MEK 1/2 (unknown origin)	33970631
Dual specificity mitogen-activated protein kinase kinase 1	IC50	=	14.0	nM	7.85	Affinity On-target Cellular interaction (Inhibition of MEK1 human HeLa-Ma Tu mat...	-
Dual specificity mitogen-activated protein kinase kinase 1	IC50	=	14.0	nM	7.85	Inhibition of MEK1 (unknown origin)	36924668
SW-620	IC50	=	15.0	nM	7.82	Antiproliferative activity against human SW620 cells harboring KRAS G12V mutant ...	28038940
H9	IC50	=	22.88	nM	7.64	SANGER: Inhibition of human H9 cell growth in a cell viability assay.	-
HL-60	IC50	=	24.59	nM	7.61	SANGER: Inhibition of human HL-60 cell growth in a cell viability assay.	-
A-375	IC50	=	31.0	nM	7.51	Antiproliferative activity against human A375 cells expressing BRAF V600E mutant...	23474388
Dual specificity mitogen-activated protein kinase kinase 1	IC50	=	31.0	nM	7.51	Inhibition of MEK1 (unknown origin) using biotinylated ERK1 as substrate incubat...	26611920
NOMO-1	IC50	=	31.97	nM	7.5	SANGER: Inhibition of human NOMO-1 cell growth in a cell viability assay.	-
HepG2	IC50	=	32.0	nM	7.5	Antiproliferative activity against human HepG2 cells harboring N-Ras mutation	26611920
DU-4475	IC50	=	33.67	nM	7.47	SANGER: Inhibition of human DU-4475 cell growth in a cell viability assay.	-
M14	IC50	=	36.89	nM	7.43	SANGER: Inhibition of human M14 cell growth in a cell viability assay.	-
Dual specificity mitogen-activated protein kinase kinase 1	Kd	=	41.0	nM	7.39	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Dual specificity mitogen-activated protein kinase kinase 2	Kd	=	52.0	nM	7.28	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878

Literature References

PubMed	DOI	Target Context	# Activities
27448918	10.1016/j.ejmech.2016.06.043	SW480	19
22037378	10.1038/nbt.1990	Tyrosine-protein kinase ABL1	15
-	10.6019/CHEMBL5674860	Colon cancer organoid	12
-	10.6019/CHEMBL5724558	Colon cancer organoid	12
22037378	10.1038/nbt.1990	Epidermal growth factor receptor	12
22037378	10.1038/nbt.1990	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	10
26254279	10.18632/oncotarget.4214	Dual specificity mitogen-activated protein kinase kinase 1	9
-	10.6019/CHEMBL4689842	U2OS	9
-	10.6019/CHEMBL5724696	U2OS	8
22037378	10.1038/nbt.1990	Mast/stem cell growth factor receptor Kit	8
27448918	10.1016/j.ejmech.2016.06.043	Molecular identity unknown	7
22037378	10.1038/nbt.1990	Receptor-type tyrosine-protein kinase FLT3	7
-	10.6019/CHEMBL5608141	Colon cancer organoid	6
-	10.1158/2159-8290.CD-23-0050	Colon cancer organoid	5
29191878	10.1126/science.aan4368	Unchecked	5
-	10.6019/CHEMBL4689842	HEK-293T	5
22037378	10.1038/nbt.1990	Proto-oncogene tyrosine-protein kinase receptor Ret	4
26611920	10.1016/j.bmcl.2015.11.004	Rattus norvegicus	4
23474388	10.1016/j.bmcl.2013.02.028	Rattus norvegicus	4
27448918	10.1016/j.ejmech.2016.06.043	HT-29	3

Data from ChEMBL 36 via Core Engine