Compound Detail

CHEMBL1091644

LINSITINIB

🧪 Phase III

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🧪 Phase III

C[C@]1(O)C[C@@H](c2nc(-c3ccc4ccc(-c5ccccc5)nc4c3)c3c(N)nccn32)C1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL1091644
Name	LINSITINIB
Phase	Phase III
Structure Type	MOL
InChI Key	PKCDDUHJAFVJJB-VLZXCDOPSA-N

Known Names

ASP-7487 Linsitinib OSI-906 OSI-906AA

463

Targets

730

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

421.5

MW (Da)

4.82

ALogP

HBA

HBD

89.3

PSA (Å²)

0.44

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Single Enantiomer

Flags

Natural Product Chemical Probe

USAN Stem	-tinib
USAN Year	2010

Extended Properties

Molecular Formula	C26H23N5O
MW	421.50
Aromatic Rings	5
Heavy Atoms	32
NP-Likeness	-0.48

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Insulin-like growth factor I receptor inhibitor	INHIBITOR	Insulin-like growth factor 1 receptor	✓	✓
Insulin receptor inhibitor	INHIBITOR	Insulin receptor	✓	✓

Indications

Adrenal Cortex Neoplasms Breast Neoplasms Carcinoma, Hepatocellular Carcinoma, Non-Small-Cell Lung Head and Neck Neoplasms Neoplasms Prostatic Neoplasms Prostatic Neoplasms, Castration-Resistant Sarcoma, Ewing Small Cell Lung Carcinoma Carcinoma, Squamous Cell Carcinoma, Squamous Cell Colorectal Neoplasms Ovarian Neoplasms Skin Neoplasms

Activity Summary

IC50 709 meas. best 8.7

Kd 19 meas. best 8.0

EC50 2 meas. best 6.98

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Insulin-like growth factor 1 receptor CHEMBL1957	IC50	8.7	7.6185	2.0	20
Mitogen-activated protein kinase 11 CHEMBL3961	Kd	8.0	8.0	10.0	1
Insulin receptor CHEMBL1981	IC50	7.8	7.245	16.0	8
Insulin receptor-related protein CHEMBL5483	IC50	7.68	6.9733	21.0	3
SW-620 CHEMBL612262	IC50	7.68	6.255	21.0	2
Mitogen-activated protein kinase; ERK1/ERK2 CHEMBL1907606	IC50	7.55	7.55	28.0	1
A4-Fuk CHEMBL2366356	IC50	7.55	7.55	28.1	1
KS-1 CHEMBL2366228	IC50	7.42	7.42	38.4	1
NIH3T3 CHEMBL614822	IC50	7.22	7.165	60.0	2
Mitogen-activated protein kinase kinase kinase kinase 2 CHEMBL5330	Kd	7.17	7.17	67.0	1
Unchecked CHEMBL612545	IC50	7.12	6.6333	75.0	3
TE-11 CHEMBL2366166	IC50	7.11	7.11	78.2	1
DU-4475 CHEMBL2366246	IC50	7.07	5.825	86.0	2
EW-1 CHEMBL2366364	IC50	7.07	7.07	85.8	1
HMV-2 cell line CHEMBL614826	IC50	7.05	7.05	88.5	1
Broad substrate specificity ATP-binding cassette transporter ABCG2 CHEMBL5393	EC50	6.98	6.98	104.0	1
COLO 205 CHEMBL614561	IC50	6.98	6.74	104.5	2
ES1 CHEMBL2366146	IC50	6.97	6.97	107.0	1
Insulin-like growth factor 1 receptor CHEMBL1957	Kd	6.86	6.86	138.0	1
GDM-1 CHEMBL2366157	IC50	6.86	6.86	136.7	1
A673 CHEMBL614517	IC50	6.82	5.9	153.0	2
BXPC-3 CHEMBL614530	IC50	6.82	5.55	150.0	2
ML-2 CHEMBL614356	IC50	6.8	6.8	159.0	1
SAOS-2 CHEMBL614894	IC50	6.78	6.78	165.3	1
MCF7 CHEMBL387	IC50	6.75	6.02	177.0	2
NCI-H1355 CHEMBL2366227	IC50	6.74	6.74	181.3	1
G-401 CHEMBL613509	IC50	6.74	6.74	182.3	1
EW-16 CHEMBL2366358	IC50	6.73	6.73	187.8	1
EW-7 CHEMBL2366112	IC50	6.72	6.72	188.8	1
Serine/threonine-protein kinase LATS1 CHEMBL6167	Kd	6.71	6.71	195.0	1
NCI-H727 CHEMBL1075545	IC50	6.7	6.7	197.9	1
Insulin receptor CHEMBL1981	Kd	6.7	6.7	202.0	1
Uncharacterized aarF domain-containing protein kinase 5 CHEMBL4105886	Kd	6.7	6.7	202.0	1
LCLC-97TM1 CHEMBL1075489	IC50	6.68	6.68	209.6	1
HT-29 CHEMBL384	IC50	6.68	6.65	210.0	2
NCI-H650 CHEMBL1075543	IC50	6.67	6.67	213.8	1
NCI-H2122 CHEMBL1075533	IC50	6.63	6.63	233.0	1
SK-N-DZ CHEMBL1075579	IC50	6.62	6.62	237.0	1
LB771-HNC CHEMBL2366099	IC50	6.59	6.59	259.1	1
LAN-6 CHEMBL2366123	IC50	6.58	6.58	263.5	1
HT-144 CHEMBL2366291	IC50	6.58	6.58	261.9	1
LS-1034 CHEMBL2366072	IC50	6.57	6.57	271.3	1
EW-18 CHEMBL2366097	IC50	6.57	6.57	270.0	1
EW-11 CHEMBL2366223	IC50	6.55	6.55	284.3	1
SNU-C1 CHEMBL2366304	IC50	6.53	6.53	293.1	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	Kd	6.51	6.51	308.0	1
RS4-11 CHEMBL2366159	IC50	6.47	6.47	337.6	1
Dual specificity mitogen-activated protein kinase kinase 1 CHEMBL3587	Kd	6.45	6.45	352.0	1
Plasmodium berghei CHEMBL612653	IC50	6.44	6.44	360.0	1
Hepatocyte growth factor receptor CHEMBL3717	Kd	6.4	6.4	395.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	6954.0	ng.hr.mL-1	Mus musculus
AUC	23123.0	ng.hr.mL-1	Rattus norvegicus
AUC	1066.0	ng.hr.mL-1	Canis lupus familiaris
AUC	6770.0	ng.hr.mL-1	Mus musculus
AUC	26741.0	ng.hr.mL-1	Mus musculus
AUC	87455.0	ng.hr.mL-1	Mus musculus
AUC	317487.0	ng.hr.mL-1	Mus musculus
AUC	42832.0	ng.hr.mL-1	Rattus norvegicus
AUC	424076.0	ng.hr.mL-1	Rattus norvegicus
AUC	1328.0	ng.hr.mL-1	Canis lupus familiaris
CL	16.98	uL.min-1.(10^6cells)-1	Rattus norvegicus
CL	17.38	mL.min-1.g-1	Homo sapiens
CL	12.0	mL.min-1.kg-1	Mus musculus
CL	4.0	mL.min-1.kg-1	Rattus norvegicus
CL	39.0	mL.min-1.kg-1	Canis lupus familiaris
Cmax	3420.0	nM	Mus musculus
Cmax	16040.0	nM	Mus musculus
Cmax	16800.0	nM	Mus musculus
Cmax	41990.0	nM	Mus musculus
Cmax	10010.0	nM	Rattus norvegicus
Cmax	34640.0	nM	Rattus norvegicus
Cmax	1200.0	nM	Canis lupus familiaris
F	84.0	%	Mus musculus
F	92.0	%	Rattus norvegicus
F	64.0	%	Canis lupus familiaris
F	98.0	%	Mus musculus
F	100.0	%	Mus musculus
F	84.0	%	Mus musculus
F	100.0	%	Mus musculus
F	74.0	%	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Insulin-like growth factor 1 receptor	IC50	=	2.0	nM	8.7	Inhibition of IGF1R (unknown origin) using poly-G1 as substrate incubated for 10...	25559205
Insulin-like growth factor 1 receptor	IC50	=	2.8	nM	8.55	Inhibition of full length IGF-1 receptor (unknown origin) autophosphorylation tr...	26951753
Insulin-like growth factor 1 receptor	IC50	=	7.6	nM	8.12	Inhibition of full length IGF-1 receptor (unknown origin) transfected in Ba/F3 c...	26951753
Mitogen-activated protein kinase 11	Kd	=	10.0	nM	8.0	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Insulin-like growth factor 1 receptor	IC50	=	12.0	nM	7.92	Inhibition of GST-tagged IGF-1R catalytic domain (unknown origin) using omnia Y ...	24900721
Insulin-like growth factor 1 receptor	IC50	=	13.0	nM	7.89	Inhibition of GST-tagged IGF-1R catalytic domain (unknown origin) using omnia Y ...	24900721
Insulin-like growth factor 1 receptor	IC50	=	14.0	nM	7.85	Inhibition of IGF-1 receptor (unknown origin) in presence of [gamma33P]ATP	26951753
Insulin receptor	IC50	=	16.0	nM	7.8	Inhibition of full length insulin receptor (unknown origin) autophosphorylation ...	26951753
Insulin receptor	IC50	=	18.0	nM	7.75	Inhibition of recombinant INSR (unknown origin) using fluorescent dye-labelled K...	24900830
Insulin-like growth factor 1 receptor	IC50	=	18.0	nM	7.75	Inhibition of IGF1R intracellular phosphorylation in human A431 cells by ELISA	20346655
SW-620	IC50	=	21.0	nM	7.68	Antiproliferative activity against human SW620 cells assessed as inhibition of c...	21425998
Insulin receptor-related protein	IC50	=	21.0	nM	7.68	Affinity Phenotypic Cellular interaction (CellTiterGlo™ luciferase-based cellula...	-
Insulin-like growth factor 1 receptor	IC50	=	21.0	nM	7.68	Affinity Phenotypic Cellular interaction (CellTiterGlo™ luciferase-based cellula...	-
Insulin receptor	IC50	=	21.0	nM	7.68	Affinity Phenotypic Cellular interaction (CellTiterGlo™ luciferase-based cellula...	-
Insulin-like growth factor 1 receptor	IC50	=	24.0	nM	7.62	Inhibition of human recombinant IGF-1 receptor in presence of 100 uM ATP treated...	21425998
Insulin-like growth factor 1 receptor	IC50	=	24.0	nM	7.62	Inhibition of human recombinant IGF-1 receptor expressed in mouse 3T3 cells trea...	21425998
Insulin-like growth factor 1 receptor	IC50	=	24.0	nM	7.62	Affinity On-target Cellular interaction (Immunoblot (IGF-1-dependent autophospho...	-
Insulin-like growth factor 1 receptor	IC50	=	24.0	nM	7.62	Inhibition of full length human IGF-1R overexpressed in mouse NIH 3T3 cells asse...	24900721
Insulin-like growth factor 1 receptor	IC50	=	24.0	nM	7.62	Inhibition of human IGF1R expressed in mouse 3T3 cells by ELISA based assay	21251824
Mitogen-activated protein kinase; ERK1/ERK2	IC50	=	28.0	nM	7.55	Inhibition of ERK1/2 phosphorylation (unknown origin) expressed in mouse 3T3 cel...	21425998

Literature References

PubMed	DOI	Target Context	# Activities
-	10.6019/CHEMBL4689842	U2OS	261
-	10.6019/CHEMBL4689842	HEK-293T	261
-	10.6019/CHEMBL4689842	Fibroblast	259
21425998	10.4155/fmc.09.89	ADMET	45
-	10.6019/CHEMBL5674860	Colon cancer organoid	12
-	10.6019/CHEMBL5724558	Colon cancer organoid	12
21425998	10.4155/fmc.09.89	Unchecked	11
-	10.6019/CHEMBL5608141	Colon cancer organoid	6
21425998	10.4155/fmc.09.89	NIH3T3	6
21425998	10.4155/fmc.09.89	Insulin-like growth factor 1 receptor	6
29191878	10.1126/science.aan4368	Unchecked	5
-	10.6019/CHEMBL4495565	SARS-CoV-2	4
24900721	10.1021/ml400160a	Insulin-like growth factor 1 receptor	4
26951753	10.1016/j.bmcl.2016.02.075	Insulin-like growth factor 1 receptor	3
26951753	10.1016/j.bmcl.2016.02.075	ADMET	3
-	10.6019/CHEMBL3832761	Plasmodium falciparum	3
26951753	10.1016/j.bmcl.2016.02.075	Unchecked	3
26951753	10.1016/j.bmcl.2016.02.075	Insulin receptor	3
36324498	10.1039/d2md00139j	ADMET	3
-	10.6019/CHEMBL4808148	Histone deacetylase 6	2

Data from ChEMBL 36 via Core Engine