Compound Detail

CHEMBL4744041

Enter ChEMBL ID:

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

Cc1cc(-c2ccnc(Nc3cnn(C)c3)n2)ccc1CNC(=O)N1CC(OC(C)C)C1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL4744041
Phase	Preclinical
Structure Type	MOL
InChI Key	BMWMKGNVAMXXCH-UHFFFAOYSA-N

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Molecular Properties

435.5

MW (Da)

3.25

ALogP

HBA

HBD

97.2

PSA (Å²)

0.59

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Unknown
Availability	Unknown
Chirality	Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula	C23H29N7O2
MW	435.53
Aromatic Rings	3
Heavy Atoms	32
NP-Likeness	-1.78

Activity Summary

IC50 19 meas. best 9.0

Kd 18 meas. best 9.52

Ki 2 meas. best 4.3

EC50 1 meas. best 6.8

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Tyrosine-protein kinase BTK CHEMBL5251	Kd	9.52	9.52	0.3	3
Tyrosine-protein kinase BTK CHEMBL5251	IC50	9.0	7.4129	1.0	14
Tyrosine-protein kinase BTK CHEMBL3259478	IC50	6.89	6.83	130.0	2
Mitogen-activated protein kinase kinase kinase 19 CHEMBL6191	Kd	6.89	6.89	130.0	2
Unchecked CHEMBL612545	EC50	6.8	6.8	160.0	1
Cyclin-dependent kinase-like 2 CHEMBL5728	Kd	6.38	6.38	420.0	2
AP2-associated protein kinase 1 CHEMBL3830	Kd	6.37	6.37	430.0	2
Tyrosine-protein kinase JAK2 CHEMBL2971	Kd	6.34	6.34	460.0	2
Cyclin-dependent kinase 7 CHEMBL3055	Kd	6.06	6.06	880.0	1
BMP-2-inducible protein kinase CHEMBL4522	Kd	5.96	5.96	1100.0	2
Serine/threonine-protein kinase RIO1 CHEMBL5975	Kd	5.92	5.92	1200.0	2
Serine/threonine-protein kinase RIO2 CHEMBL6000	Kd	5.62	5.62	2400.0	2
Early activation antigen CD69 CHEMBL3308911	IC50	5.52	5.52	3000.0	1
Unchecked CHEMBL612545	IC50	5.38	5.38	4200.0	1
Histamine H2 receptor CHEMBL1941	IC50	4.58	4.58	26500.0	1
Cytochrome P450 3A4 CHEMBL340	Ki	4.3	4.3	50000.0	2

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	11907.0	ng.hr.mL-1	Rattus norvegicus
AUC	1938.0	ng.hr.mL-1	Canis lupus familiaris
AUC	2346.0	ng.hr.mL-1	Macaca fascicularis
AUC	376000.0	ng.hr.mL-1	Rattus norvegicus
AUC	129000.0	ng.hr.mL-1	Macaca fascicularis
AUC	11907.0	ng.hr.mL-1	Rattus norvegicus
AUC	1938.0	ng.hr.mL-1	Canis lupus familiaris
CL	1.0	%	Rattus norvegicus
CL	3.0	mL.min-1.kg-1	Rattus norvegicus
CL	6.0	%	Rattus norvegicus
CL	11.0	mL.min-1.kg-1	Canis lupus familiaris
CL	37.0	%	Canis lupus familiaris
CL	11.0	mL.min-1.kg-1	Macaca fascicularis
CL	26.0	%	Macaca fascicularis
CL	3.0	mL.min-1.kg-1	Rattus norvegicus
CL	11.0	mL.min-1.kg-1	Canis lupus familiaris
Cmax	6704.48	nM	Rattus norvegicus
Cmax	1497.03	nM	Canis lupus familiaris
Cmax	647.49	nM	Macaca fascicularis
Cmax	6704.48	nM	Rattus norvegicus
Cmax	1497.03	nM	Canis lupus familiaris
F	48.0	%	Rattus norvegicus
F	26.0	%	Canis lupus familiaris
F	32.0	%	Macaca fascicularis
F	48.0	%	Rattus norvegicus
F	26.0	%	Canis lupus familiaris
Fu	0.059	-	Homo sapiens
Fu	0.0128	-	Rattus norvegicus
Fu	0.0362	-	Macaca fascicularis
Fu	0.113	-	Canis lupus familiaris

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Tyrosine-protein kinase BTK	Kd	=	0.3	nM	9.52	Selectivity interaction (KINOMEscan (DiscoverX, competition-binding assay)) EUB0...	-
Tyrosine-protein kinase BTK	Kd	=	0.3	nM	9.52	Affinity Biochemical interaction: (Competition-binding assay (DiscoverX)) EUB000...	-
Tyrosine-protein kinase BTK	Kd	=	0.3	nM	9.52	Binding affinity to wild-type human full length BTK (M1 to S659 residues) expres...	32696648
Tyrosine-protein kinase BTK	IC50	=	1.0	nM	9.0	Inhibition of recombinant human full-length N-terminal His6-tagged BTK expressed...	32696648
Tyrosine-protein kinase BTK	IC50	=	1.0	nM	9.0	Inhibition of human BTK using fluorescein-labeled polyGAT peptide as substrate i...	34734694
Tyrosine-protein kinase BTK	IC50	=	1.0	nM	9.0	Selectivity interaction (Time-resolved fluorescence (TRF) assay) EUB0001868a BTK	-
Tyrosine-protein kinase BTK	IC50	=	54.0	nM	7.27	Affinity Phenotypic Cellular interaction: (SLE IC-induced neutrophil ROS inducti...	-
Tyrosine-protein kinase BTK	IC50	=	54.0	nM	7.27	Inhibition of BTK in human whole blood derived neutrophils assessed as reduction...	32696648
Tyrosine-protein kinase BTK	IC50	=	63.0	nM	7.2	Inhibition of BTK in human PBMC assessed as suppression of TNFalpha/FcgammaR-ind...	32696648
Tyrosine-protein kinase BTK	IC50	=	63.0	nM	7.2	Affinity Phenotypic Cellular interaction: (IgG-mediated (plate bound) monocyte c...	-
Tyrosine-protein kinase BTK	IC50	=	100.0	nM	7.0	Inhibition of BTK phosphorylation in human whole blood assessed as reduction in ...	34734694
Tyrosine-protein kinase BTK	IC50	=	110.0	nM	6.96	Inhibition of BTK in human PBMC assessed as reduction in anti-IgD-induced B cell...	32696648
Tyrosine-protein kinase BTK	IC50	=	111.0	nM	6.96	Affinity Phenotypic Cellular interaction: (Anti-IgD-induced B cell activation in...	-
Tyrosine-protein kinase BTK	IC50	=	120.0	nM	6.92	Inhibition of BTK in human whole blood assessed as reduction in BTK phosphorylat...	32696648
Tyrosine-protein kinase BTK	IC50	=	120.0	nM	6.92	Affinity Phenotypic Cellular interaction: (Phosphorylation of BTK in human whole...	-
Tyrosine-protein kinase BTK	IC50	=	130.0	nM	6.89	In vivo inhibition of BTK in TI-2 antigen/ NP-Ficoll-induced DBA1 mouse immunize...	32696648
Mitogen-activated protein kinase kinase kinase 19	Kd	=	130.0	nM	6.89	Selectivity interaction (KINOMEscan (DiscoverX, competition binding assay)) EUB0...	-
Mitogen-activated protein kinase kinase kinase 19	Kd	=	130.0	nM	6.89	Binding affinity to wild-type human partial length YSK4 (T1019 to H1328 residues...	32696648
Unchecked	EC50	=	160.0	nM	6.8	In vivo inhibition of BTK-dependent B cell activation in TI-2 antigen/ NP-Ficoll...	32696648
Tyrosine-protein kinase BTK	IC50	=	170.0	nM	6.77	Inhibition of BTK in DBA1 mouse whole blood assessed as reduction in BTK phospho...	32696648

Literature References

PubMed	DOI	Target Context	# Activities
32696648	10.1021/acs.jmedchem.0c00702	ADMET	66
32696648	10.1021/acs.jmedchem.0c00702	Unchecked	25
34734694	10.1021/acs.jmedchem.1c00926	ADMET	17
32696648	10.1021/acs.jmedchem.0c00702	Tyrosine-protein kinase BTK	16
-	10.6019/CHEMBL5444388	Tyrosine-protein kinase BTK	10
32696648	10.1021/acs.jmedchem.0c00702	No relevant target	6
-	10.6019/CHEMBL5303304	Fibroblast	6
34734694	10.1021/acs.jmedchem.1c00926	No relevant target	5
-	10.6019/CHEMBL5303304	U2OS	5
32696648	10.1021/acs.jmedchem.0c00702	Cytochrome P450 3A4	5
-	10.6019/CHEMBL5303304	HEK-293T	4
34734694	10.1021/acs.jmedchem.1c00926	Tyrosine-protein kinase BTK	3
-	10.6019/CHEMBL5465560	Tyrosine-protein kinase BTK	3
32696648	10.1021/acs.jmedchem.0c00702	Histamine H2 receptor	2
32696648	10.1021/acs.jmedchem.0c00702	Cytochrome P450 1A2	2
32696648	10.1021/acs.jmedchem.0c00702	Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha	2
32696648	10.1021/acs.jmedchem.0c00702	Tyrosine-protein kinase JAK2	2
32696648	10.1021/acs.jmedchem.0c00702	AP2-associated protein kinase 1	2
32696648	10.1021/acs.jmedchem.0c00702	Serine/threonine-protein kinase RIO1	2
32696648	10.1021/acs.jmedchem.0c00702	Mitogen-activated protein kinase kinase kinase 19	2

Data from ChEMBL 36 via Core Engine