Compound Detail

CHEMBL2178352

Enter ChEMBL ID:

Free Research Context This compound will appear in recent viewed items on the research home for this browser.

CN1CCN(c2ccc(Nc3ncc4nc(Nc5ccccc5)n(C5CCCC5)c4n3)cc2)CC1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL2178352
Phase	Preclinical
Structure Type	MOL
InChI Key	QPOURHROVVCOHC-UHFFFAOYSA-N

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Molecular Properties

468.6

MW (Da)

5.18

ALogP

HBA

HBD

74.1

PSA (Å²)

0.40

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Availability	Unknown
Chirality	Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula	C27H32N8
MW	468.61
Aromatic Rings	4
Heavy Atoms	35
NP-Likeness	-1.27

Activity Summary

IC50 43 meas. best 9.66

Kd 9 meas. best 9.4

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
PC-9 CHEMBL614102	IC50	9.66	9.66	0.2	1
Unchecked CHEMBL612545	Kd	9.4	9.3333	0.4	3
Epidermal growth factor receptor CHEMBL203	Kd	9.3	9.1517	0.5	6
HCC827 CHEMBL4296422	IC50	9.09	8.5233	0.8	3
Epidermal growth factor receptor CHEMBL203	IC50	9.0	7.6	1.0	6
Vascular endothelial growth factor receptor 2 CHEMBL279	IC50	8.15	7.925	7.0	2
FaDu CHEMBL612250	IC50	7.82	7.82	15.0	1
Receptor tyrosine-protein kinase erbB-4 CHEMBL3009	IC50	7.52	7.52	30.0	1
NCI-H292 CHEMBL614733	IC50	7.35	7.35	45.0	1
Receptor tyrosine-protein kinase erbB-2 CHEMBL1824	IC50	7.22	7.22	60.0	1
Calu-3 CHEMBL614534	IC50	6.92	6.92	120.0	1
A-431 CHEMBL614069	IC50	6.92	6.855	120.0	2
Mitogen-activated protein kinase 14 CHEMBL260	IC50	6.64	6.64	230.0	1
Proto-oncogene tyrosine-protein kinase Src CHEMBL267	IC50	6.54	6.54	290.0	1
NCI-H1975 CHEMBL614348	IC50	6.47	6.4267	342.0	3
Mast/stem cell growth factor receptor Kit CHEMBL1936	IC50	6.27	6.27	540.0	1
Lysine--tRNA ligase CHEMBL5575	IC50	6.14	6.14	720.0	1
Unchecked CHEMBL612545	IC50	5.96	5.495	1100.0	2
Tyrosine-protein kinase JAK2 CHEMBL2971	IC50	5.92	5.92	1200.0	1
Mitogen-activated protein kinase 9 CHEMBL4179	IC50	5.82	5.82	1500.0	1
ALK tyrosine kinase receptor CHEMBL4247	IC50	5.64	5.64	2300.0	1
Tyrosine-protein kinase JAK3 CHEMBL2148	IC50	5.58	5.58	2600.0	1
HCT-116 CHEMBL394	IC50	5.52	5.52	3000.0	1
MAP kinase-interacting serine/threonine-protein kinase 2 CHEMBL4204	IC50	5.5	5.5	3200.0	1
Tyrosine-protein kinase JAK1 CHEMBL2835	IC50	5.48	5.48	3300.0	1
Protein kinase C theta type CHEMBL3920	IC50	5.44	5.44	3600.0	1
MDA-MB-231 CHEMBL400	IC50	5.3	5.3	5000.0	1
Serine/threonine-protein kinase N1 CHEMBL3384	IC50	5.21	5.21	6100.0	1
Hepatocyte growth factor receptor CHEMBL3717	IC50	5.19	5.19	6400.0	1
MAP kinase-interacting serine/threonine-protein kinase 1 CHEMBL4718	IC50	5.17	5.17	6700.0	1
Non-receptor tyrosine-protein kinase TYK2 CHEMBL3553	IC50	5.17	5.17	6700.0	1
Protein kinase C alpha type CHEMBL299	IC50	5.17	5.17	6700.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	2140.0	ng.hr.mL-1	Rattus norvegicus
CL	162.0	mL.min-1.kg-1	Rattus norvegicus
Cmax	490.81	nM	Rattus norvegicus
T1/2	4.86	hr	Rattus norvegicus
Tmax	1.0	hr	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
PC-9	IC50	=	0.22	nM	9.66	Cytotoxicity against human PC9 cells incubated for 72 hrs by MTT assay	23116168
Unchecked	Kd	=	0.4	nM	9.4	Binding affinity to wild type EGFR 747-E749del, A750P mutant by KINOMEscan kinas...	23116168
Epidermal growth factor receptor	Kd	=	0.5	nM	9.3	Binding affinity to wild type EGFR G719S mutant by KINOMEscan kinase binding ass...	23116168
Unchecked	Kd	=	0.5	nM	9.3	Binding affinity to wild type EGFR L747-S752del, Sins mutant by KINOMEscan kinas...	23116168
Unchecked	Kd	=	0.5	nM	9.3	Binding affinity to wild type EGFR E646-A750del mutant by KINOMEscan kinase bind...	23116168
Epidermal growth factor receptor	Kd	=	0.6	nM	9.22	Binding affinity to wild type EGFR by KINOMEscan kinase binding assay	23116168
Epidermal growth factor receptor	Kd	=	0.6	nM	9.22	Binding affinity to wild type EGFR L858R mutant by KINOMEscan kinase binding ass...	23116168
Epidermal growth factor receptor	Kd	=	0.6	nM	9.22	Binding affinity to wild type EGFR L861Q mutant by KINOMEscan kinase binding ass...	23116168
Epidermal growth factor receptor	Kd	=	0.7	nM	9.15	Binding affinity to wild type EGFR G719C mutant by KINOMEscan kinase binding ass...	23116168
HCC827	IC50	=	0.82	nM	9.09	Antiproliferative activity against human HCC827 cells expressing EGFR del19 muta...	32883633
HCC827	IC50	=	0.93	nM	9.03	Antiproliferative activity against human HCC827 cells expressing EGFR deletion19...	35254067
Epidermal growth factor receptor	IC50	=	1.0	nM	9.0	Inhibition Assay: The object of this assay was to test the inventive compounds f...	-
Epidermal growth factor receptor	IC50	=	1.0	nM	9.0	Inhibition Assay: The object of this assay was to test the inventive compounds f...	-
Epidermal growth factor receptor	Kd	=	1.6	nM	8.8	Binding affinity to wild type EGFR L858R and T790M mutant by KINOMEscan kinase b...	23116168
Epidermal growth factor receptor	IC50	=	4.0	nM	8.4	Inhibition of human recombinant EGFR by radiometric kinase assay	23116168
Vascular endothelial growth factor receptor 2	IC50	=	7.0	nM	8.15	Inhibition Assay: The object of this assay was to test the inventive compounds f...	-
FaDu	IC50	=	15.0	nM	7.82	Cytotoxicity against human FADU cells incubated for 72 hrs by MTT assay	23116168
Vascular endothelial growth factor receptor 2	IC50	=	20.0	nM	7.7	Inhibition of human recombinant VEGFR2 by radiometric kinase assay	23116168
Receptor tyrosine-protein kinase erbB-4	IC50	=	30.0	nM	7.52	Inhibition of human recombinant ERBB4 by radiometric kinase assay	23116168
HCC827	IC50	=	35.9	nM	7.45	Antiproliferative activity against human HCC827 cells after 72 hrs by MTT assay	29576272

Literature References

PubMed	DOI	Target Context	# Activities
23116168	10.1021/jm301365e	Epidermal growth factor receptor	16
23116168	10.1021/jm301365e	Unchecked	7
23116168	10.1021/jm301365e	Rattus norvegicus	6
23116168	10.1021/jm301365e	NON-PROTEIN TARGET	6
23116168	10.1021/jm301365e	NCI-H1975	5
23116168	10.1021/jm301365e	Mus musculus	3
29576272	10.1016/j.bmc.2018.03.025	HCC827	2
23116168	10.1021/jm301365e	FaDu	1
23116168	10.1021/jm301365e	A-431	1
23116168	10.1021/jm301365e	NCI-H292	1
23116168	10.1021/jm301365e	Calu-3	1
23116168	10.1021/jm301365e	PC-9	1
23116168	10.1021/jm301365e	Mitogen-activated protein kinase 12	1
23116168	10.1021/jm301365e	Mitogen-activated protein kinase 14	1
23116168	10.1021/jm301365e	Serine/threonine-protein kinase WNK1	1
23116168	10.1021/jm301365e	Vascular endothelial growth factor receptor 2	1
23116168	10.1021/jm301365e	Non-receptor tyrosine-protein kinase TYK2	1
23116168	10.1021/jm301365e	MDA-MB-231	1
23116168	10.1021/jm301365e	Rho-associated protein kinase 2	1
35254067	10.1021/acs.jmedchem.1c01827	A-431	1

Data from ChEMBL 36 via Core Engine