Compound Detail

CHEMBL1229592

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C=CC(=O)Nc1cccc(Oc2nc(Nc3ccc(N4CCN(C)CC4)cc3OC)ncc2Cl)c1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL1229592
Phase	Preclinical
Structure Type	MOL
InChI Key	ITTRLTNMFYIYPA-UHFFFAOYSA-N

Targets

190

Activities

Assay Types

PK Parameters

Publications

Known Names

Molecular Properties

495.0

MW (Da)

4.55

ALogP

HBA

HBD

91.8

PSA (Å²)

0.44

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Availability	Unknown
Chirality	Unknown

Flags

First in Class Prodrug Chemical Probe

Extended Properties

Molecular Formula	C25H27ClN6O3
MW	494.98
Aromatic Rings	3
Heavy Atoms	35
NP-Likeness	-1.55

Activity Summary

IC50 145 meas. best 10.4

Kd 28 meas. best 9.52

EC50 17 meas. best 8.7

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Epidermal growth factor receptor CHEMBL203	IC50	10.4	8.0023	0.0	64
Epidermal growth factor receptor CHEMBL203	Kd	9.52	7.77	0.3	13
BaF3 CHEMBL614524	IC50	8.7	7.5617	2.0	12
NON-PROTEIN TARGET CHEMBL3879801	EC50	8.7	7.5633	2.0	3
HCC827 CHEMBL4296422	IC50	8.3	8.3	5.0	1
NON-PROTEIN TARGET CHEMBL3879801	IC50	8.15	7.48	7.0	9
NUAK family SNF1-like kinase 2 CHEMBL5698	Kd	8.0	8.0	10.0	1
PC-9 CHEMBL614102	EC50	7.85	7.645	14.0	2
PC-9 CHEMBL614102	IC50	7.85	7.5767	14.0	3
HCC827 CHEMBL4296422	EC50	7.7	7.7	20.0	1
NUAK family SNF1-like kinase 1 CHEMBL5784	IC50	7.6	7.6	25.0	1
Epidermal growth factor receptor CHEMBL203	EC50	7.58	7.166	26.0	5
NCI-H1975 CHEMBL614348	IC50	7.57	7.2563	27.0	16
Receptor tyrosine-protein kinase erbB-4 CHEMBL3009	Kd	7.55	7.55	28.0	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	Kd	7.48	7.48	33.0	1
Tyrosine-protein kinase BTK CHEMBL5251	Kd	7.44	7.44	36.0	1
Tyrosine-protein kinase ITK/TSK CHEMBL2959	Kd	7.37	7.37	43.0	1
Unchecked CHEMBL612545	IC50	7.33	6.104	47.0	5
Cytoplasmic tyrosine-protein kinase BMX CHEMBL3834	IC50	7.32	7.32	48.0	1
Focal adhesion kinase 1 CHEMBL2695	Kd	7.11	7.11	78.0	1
NCI-H1975 CHEMBL614348	EC50	7.05	7.025	90.0	2
NCI-H3255 CHEMBL4296476	IC50	7.05	7.05	89.0	1
Cyclin-G-associated kinase CHEMBL4355	Kd	7.04	7.04	91.0	1
NUAK family SNF1-like kinase 1 CHEMBL5784	Kd	7.04	7.04	91.0	1
Serine/threonine-protein kinase PLK4 CHEMBL3788	Kd	7.0	7.0	100.0	1
eIF-2-alpha kinase GCN2 CHEMBL5358	Kd	6.85	6.85	140.0	1
Tyrosine-protein kinase JAK3 CHEMBL2148	Kd	6.82	6.82	150.0	2
Tyrosine-protein kinase Blk CHEMBL2250	Kd	6.66	6.66	220.0	1
ALK tyrosine kinase receptor CHEMBL4247	Kd	6.52	6.52	300.0	1
Tyrosine-protein kinase Blk CHEMBL2250	IC50	6.12	6.12	756.0	1
ADMET CHEMBL612558	IC50	6.09	5.695	811.0	6
Serine/threonine-protein kinase DCLK3 CHEMBL6123	Kd	6.04	6.04	910.0	1
ALK tyrosine kinase receptor CHEMBL4247	IC50	6.0	6.0	990.0	1
A-431 CHEMBL614069	IC50	5.98	5.9338	1042.0	8
A549 CHEMBL392	IC50	5.73	5.595	1870.0	6
Calu-3 CHEMBL614534	IC50	5.71	5.71	1960.0	1
Dipeptidyl peptidase 1 CHEMBL2252	IC50	5.68	5.68	2100.0	2
A-431 CHEMBL614069	EC50	5.66	5.66	2200.0	2
Tyrosine-protein kinase JAK3 CHEMBL2148	IC50	5.55	5.55	2820.0	1
HT-29 CHEMBL384	IC50	5.53	5.53	2950.0	2
Tyrosine-protein kinase JAK2 CHEMBL2971	IC50	5.42	5.42	3760.0	1
A549 CHEMBL392	EC50	5.4	5.4	3990.0	1
EML4-ALK CHEMBL3883330	EC50	5.2	5.2	6258.0	1
Tyrosine-protein kinase ABL1 CHEMBL3099	IC50	5.01	4.9	9690.0	2

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	956.0	ng.hr.mL-1	Mus musculus
AUC	976.0	ng.hr.mL-1	Mus musculus
AUC	2393.0	ng.hr.mL-1	Mus musculus
AUC	2396.0	ng.hr.mL-1	Mus musculus
CL	3.31	uL.min-1.(10^6cells)-1	Homo sapiens
CL	79.43	uL.min-1.(10^6cells)-1	Rattus norvegicus
CL	17.1	mL.min-1.kg-1	Mus musculus
Cmax	866.7	nM	Mus musculus
F	24.5	%	Mus musculus
MRT	1.51	hr	Mus musculus
MRT	3.98	hr	Mus musculus
T1/2	1.76	hr	Mus musculus
T1/2	2.46	hr	Mus musculus
Tmax	0.25	hr	Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Epidermal growth factor receptor	IC50	=	0.04	nM	10.4	Inhibition of recombinant human N-terminal GST tagged EGFR L858R/T790M double mu...	29523467
Epidermal growth factor receptor	IC50	=	0.19	nM	9.72	Inhibition of GST-tagged human recombinant EGFR catalytic domain (668 to 1210 am...	25975640
Epidermal growth factor receptor	Kd	=	0.3	nM	9.52	Binding affinity to partial length human EGFR L858R/T790M double mutant expresse...	26882288
Epidermal growth factor receptor	IC50	=	0.3	nM	9.52	Inhibition of recombinant human N-terminal GST tagged EGFR d746-750 mutant (669 ...	29523467
Epidermal growth factor receptor	IC50	=	0.42	nM	9.38	Inhibition of GST-tagged human recombinant EGFR catalytic domain (668 to 1210 am...	25975640
Epidermal growth factor receptor	IC50	=	0.66	nM	9.18	Inhibition of EGFR T790M/L858R double mutant (unknown origin) using Tyr 4 peptid...	24053674
Epidermal growth factor receptor	IC50	=	0.7	nM	9.15	Inhibition of EGFR L858R/T790M mutant (unknown origin) after 1.5 hr by FRET-base...	24607591
Epidermal growth factor receptor	IC50	=	0.8	nM	9.1	Inhibition of EGFR L858R/T790M double mutant (unknown origin) after 1.5 hrs by F...	23668441
Epidermal growth factor receptor	IC50	=	0.8	nM	9.1	Inhibition of EGFR L858R/T790M mutant (unknown origin) using Tyr 4 peptide as su...	23792318
Epidermal growth factor receptor	IC50	=	0.8	nM	9.1	Inhibition of recombinant human N-terminal GST tagged EGFR L858R mutant (669 to ...	29523467
Epidermal growth factor receptor	IC50	=	1.02	nM	8.99	EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants...	-
Epidermal growth factor receptor	IC50	=	1.1	nM	8.96	Inhibition of EGFR L858R mutant (unknown origin)	28482151
Epidermal growth factor receptor	Kd	=	1.2	nM	8.92	Binding affinity to wild type partial length human EGFR expressed in bacterial s...	26882288
Epidermal growth factor receptor	IC50	=	1.4	nM	8.85	Inhibition of wild-type EGFR (unknown origin)	28482151
Epidermal growth factor receptor	IC50	=	1.7	nM	8.77	Inhibition of EGFR (unknown origin) using biotin-labelled peptide as substrate p...	31145622
Epidermal growth factor receptor	IC50	=	1.82	nM	8.74	Inhibition of EGFR kinase L858R/T790M double mutant (unknown origin) after 1.5 h...	-
Epidermal growth factor receptor	IC50	=	1.88	nM	8.73	Inhibition of EGFR L858R/T790M mutant after 1.5 hr by FRET assay	22339342
BaF3	IC50	=	2.0	nM	8.7	Antiproliferative activity against mouse BaF3 cells harboring EGFR E746_A750/T79...	20033049
BaF3	IC50	=	2.0	nM	8.7	Antiproliferative activity against mouse BaF3 cells harboring EGFR L858R mutant ...	20033049
Epidermal growth factor receptor	IC50	=	1.98	nM	8.7	Inhibition of N-terminal GST-tagged human recombinant EGFR T790M mutant (668 to ...	33239261

Literature References

PubMed	DOI	Target Context	# Activities
-	10.6019/CHEMBL4689842	U2OS	262
-	10.6019/CHEMBL4689842	HEK-293T	260
-	10.6019/CHEMBL4689842	Fibroblast	259
20033049	10.1038/nature08622	ADMET	33
20033049	10.1038/nature08622	Epidermal growth factor receptor	21
22339342	10.1021/jm201591k	Epidermal growth factor receptor	19
28974338	10.1016/j.bmcl.2017.09.048	Epidermal growth factor receptor	15
20033049	10.1038/nature08622	Mus musculus	14
20033049	10.1038/nature08622	BaF3	13
20033049	10.1038/nature08622	Unchecked	12
28528303	10.1016/j.ejmech.2017.04.079	Epidermal growth factor receptor	8
28850922	10.1016/j.ejmech.2017.08.035	Epidermal growth factor receptor	7
-	10.1039/C5MD00208G	Epidermal growth factor receptor	7
23792318	10.1016/j.ejmech.2013.05.026	Epidermal growth factor receptor	6
23668441	10.1021/jm400463q	Epidermal growth factor receptor	6
-	10.1039/C2MD20078C	Epidermal growth factor receptor	5
24607591	10.1016/j.ejmech.2014.02.032	No relevant target	5
21208802	10.1016/j.bmcl.2010.12.036	NON-PROTEIN TARGET	5
26451770	10.1016/j.ejmech.2015.09.031	Epidermal growth factor receptor	5
26882288	10.1021/acs.jmedchem.5b00840	BaF3	5

Data from ChEMBL 36 via Core Engine