Compound Detail

CHEMBL4281823

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CCn1cc(-c2ccc3c(c2)CCN3C(=O)Cc2cccc(OC(F)(F)F)c2)c2c(N)ncnc21

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL4281823
Phase	Preclinical
Structure Type	MOL
InChI Key	APPXQUDJLJXULP-UHFFFAOYSA-N

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Molecular Properties

481.5

MW (Da)

4.73

ALogP

HBA

HBD

86.3

PSA (Å²)

0.45

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Availability	Unknown
Chirality	Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula	C25H22F3N5O2
MW	481.48
Aromatic Rings	4
Heavy Atoms	35
NP-Likeness	-1.19

Activity Summary

IC50 49 meas. best 8.15

EC50 4 meas. best 9.29

Kd 2 meas. best 8.36

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
J774.A1 CHEMBL614040	EC50	9.29	9.29	0.5	1
L929 CHEMBL612267	EC50	9.0	9.0	1.0	1
HT-29 CHEMBL384	EC50	8.73	8.73	1.9	1
Receptor-interacting serine/threonine-protein kinase 1 CHEMBL5464	Kd	8.36	8.36	4.4	1
NT-3 growth factor receptor CHEMBL5608	IC50	8.15	8.15	7.0	1
BDNF/NT-3 growth factors receptor CHEMBL4898	IC50	8.1	8.1	8.0	1
Receptor-interacting serine/threonine-protein kinase 1 CHEMBL5464	IC50	7.96	7.96	11.0	1
U-937 CHEMBL612794	EC50	7.94	7.94	11.6	1
Vascular endothelial growth factor receptor 3 CHEMBL1955	IC50	7.7	7.7	20.0	1
Eukaryotic translation initiation factor 2-alpha kinase 1 CHEMBL6029	IC50	7.58	7.58	26.0	1
High affinity nerve growth factor receptor CHEMBL2815	IC50	7.58	7.58	26.0	1
Tyrosine-protein kinase Mer CHEMBL5331	IC50	7.54	7.54	29.0	1
Tyrosine-protein kinase receptor UFO CHEMBL4895	IC50	7.46	7.46	35.0	1
Epithelial discoidin domain-containing receptor 1 CHEMBL5319	IC50	7.46	7.46	35.0	1
Mitogen-activated protein kinase kinase kinase kinase 5 CHEMBL4852	IC50	7.43	7.43	37.0	1
Tyrosine-protein kinase Lck CHEMBL258	IC50	7.37	7.37	43.0	1
Mitogen-activated protein kinase kinase kinase 10 CHEMBL2873	IC50	7.3	7.3	50.0	1
Serine/threonine-protein kinase 3 CHEMBL4708	IC50	7.3	7.3	50.0	1
Mitogen-activated protein kinase kinase kinase 9 CHEMBL2872	IC50	7.28	7.28	52.0	1
Tyrosine-protein kinase ITK/TSK CHEMBL2959	IC50	7.22	7.22	60.0	1
Proto-oncogene tyrosine-protein kinase receptor Ret CHEMBL2041	IC50	7.18	7.18	66.0	1
Angiopoietin-1 receptor CHEMBL4128	IC50	7.12	7.12	75.0	1
Vascular endothelial growth factor receptor 1 CHEMBL1868	IC50	7.12	7.12	76.0	1
Tyrosine-protein kinase Lyn CHEMBL3905	IC50	7.07	7.07	85.0	1
Focal adhesion kinase 1 CHEMBL2695	IC50	7.05	7.05	89.0	1
Hepatocyte growth factor receptor CHEMBL3717	IC50	7.04	7.04	92.0	1
Serine/threonine-protein kinase WNK3 CHEMBL6055	IC50	7.01	7.01	97.0	1
Mitogen-activated protein kinase kinase kinase kinase 3 CHEMBL5432	IC50	6.97	6.97	106.0	1
Protein-tyrosine kinase 6 CHEMBL4601	IC50	6.96	6.96	111.0	1
Interferon-induced, double-stranded RNA-activated protein kinase CHEMBL5785	IC50	6.94	6.81	116.0	2
Discoidin domain-containing receptor 2 CHEMBL5122	IC50	6.94	6.94	116.0	1
Fibroblast growth factor receptor 1 CHEMBL3650	IC50	6.9	6.9	127.0	1
Tyrosine-protein kinase Blk CHEMBL2250	IC50	6.86	6.86	138.0	1
Tyrosine-protein kinase HCK CHEMBL3234	IC50	6.85	6.85	142.0	1
Proto-oncogene tyrosine-protein kinase Src CHEMBL267	IC50	6.76	6.72	173.0	2
Mast/stem cell growth factor receptor Kit CHEMBL1936	IC50	6.74	6.74	182.0	1
Tyrosine-protein kinase Fyn CHEMBL1841	IC50	6.73	6.73	187.0	1
Ephrin type-A receptor 7 CHEMBL4602	IC50	6.72	6.72	190.0	1
Aurora kinase B CHEMBL2185	IC50	6.68	6.68	210.0	1
Ephrin type-A receptor 8 CHEMBL4134	IC50	6.63	6.63	233.0	1
Mitogen-activated protein kinase kinase kinase 2 CHEMBL5914	IC50	6.59	6.59	255.0	1
Serine/threonine-protein kinase Nek2 CHEMBL3835	IC50	6.57	6.57	268.0	1
Tyrosine-protein kinase ABL2 CHEMBL4014	IC50	6.51	6.51	306.0	1
Ephrin type-A receptor 2 CHEMBL2068	IC50	6.47	6.47	341.0	1
Tyrosine-protein kinase ABL1 CHEMBL1862	IC50	6.47	6.47	335.0	1
Mitogen-activated protein kinase 13 CHEMBL2939	IC50	6.46	6.46	347.0	1
Tyrosine-protein kinase Yes CHEMBL2073	IC50	6.42	6.42	384.0	1
Mitogen-activated protein kinase kinase kinase kinase 2 CHEMBL5330	IC50	6.41	6.41	387.0	1
Mitogen-activated protein kinase kinase kinase 20 CHEMBL3886	IC50	6.34	6.34	457.0	1
Tyrosine-protein kinase Fgr CHEMBL4454	IC50	6.33	6.33	470.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	14855.21	ng.hr.mL-1	Rattus norvegicus
CL	11.22	mL.min-1.kg-1	Rattus norvegicus
Cmax	4791.48	nM	Rattus norvegicus
F	58.0	%	Rattus norvegicus
T1/2	2.254	hr	Rattus norvegicus
Tmax	2.0	hr	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
J774.A1	EC50	=	0.517	nM	9.29	Cytoprotection against TNFalpha/Smac-mimetic/z-VAD-FMK induced necroptosis in mo...	30480444
L929	EC50	=	0.999	nM	9.0	Cytoprotection against TNFalpha/z-VAD-FMK induced necroptosis in mouse L929 cell...	30480444
HT-29	EC50	=	1.861	nM	8.73	Cytoprotection against TNFalpha/Smac-mimetic/z-VAD-FMK induced necroptosis in hu...	30480444
Receptor-interacting serine/threonine-protein kinase 1	Kd	=	4.4	nM	8.36	Binding affinity to wild-type human partial length RIPK1 (M1 to K305 residues) e...	30480444
NT-3 growth factor receptor	IC50	=	7.0	nM	8.15	Inhibition of recombinant human TrkC (510 to end residues) using GEEPLYWSFPAKK a...	30480444
BDNF/NT-3 growth factors receptor	IC50	=	8.0	nM	8.1	Inhibition of recombinant human TrkB (455 to end residues) using poly(Glu, Tyr) ...	30480444
Receptor-interacting serine/threonine-protein kinase 1	IC50	=	11.0	nM	7.96	Inhibition of recombinant human RIPK1 (8 to 322 residues) using myelin basic pro...	30480444
U-937	EC50	=	11.55	nM	7.94	Cytoprotection against TNFalpha/Smac-mimetic/z-VAD-FMK induced necroptosis in hu...	30480444
Vascular endothelial growth factor receptor 3	IC50	=	20.0	nM	7.7	Inhibition of recombinant human Flt4 V1128L/H1146R double mutant (800 to end res...	30480444
High affinity nerve growth factor receptor	IC50	=	26.0	nM	7.58	Inhibition of recombinant human TrkA (440 to end residues) using KKKSPGEYVNIEF a...	30480444
Eukaryotic translation initiation factor 2-alpha kinase 1	IC50	=	26.0	nM	7.58	Inhibition of recombinant human HRI (140 to end residues) using RSRSRSRSRSRSR as...	30480444
Tyrosine-protein kinase Mer	IC50	=	29.0	nM	7.54	Inhibition of recombinant human Mer H628Q/R794A double mutant (557 to 882 residu...	30480444
Tyrosine-protein kinase receptor UFO	IC50	=	35.0	nM	7.46	Inhibition of recombinant human Axl Q764R mutant (473 to end residues) using KKS...	30480444
Epithelial discoidin domain-containing receptor 1	IC50	=	35.0	nM	7.46	Inhibition of recombinant human DDR1 (492 to end residues) using KKKSPGEYVNIEF a...	30480444
Mitogen-activated protein kinase kinase kinase kinase 5	IC50	=	37.0	nM	7.43	Inhibition of recombinant full length human MAP4K5 using myelin basic protein as...	30480444
Tyrosine-protein kinase Lck	IC50	=	43.0	nM	7.37	Inhibition of recombinant full length human Lck using KVEKIGEGTYGVV as substrate...	30480444
Serine/threonine-protein kinase 3	IC50	=	50.0	nM	7.3	Inhibition of recombinant human MST2 (2 to end residues) using myelin basic prot...	30480444
Mitogen-activated protein kinase kinase kinase 10	IC50	=	50.0	nM	7.3	Inhibition of recombinant human MLK2 (1 to 449 residues) using myelin basic prot...	30480444
Mitogen-activated protein kinase kinase kinase 9	IC50	=	52.0	nM	7.28	Inhibition of recombinant human MLK1 (134 to 414 residues) using casein as subst...	30480444
Tyrosine-protein kinase ITK/TSK	IC50	=	60.0	nM	7.22	Inhibition of recombinant human Itk (352 to 617 residues) using myelin basic pro...	30480444

Literature References

PubMed	DOI	Target Context	# Activities
30480444	10.1021/acs.jmedchem.8b01652	Rattus norvegicus	7
30480444	10.1021/acs.jmedchem.8b01652	HT-29	5
30480444	10.1021/acs.jmedchem.8b01652	Receptor-interacting serine/threonine-protein kinase 1	5
30480444	10.1021/acs.jmedchem.8b01652	B16	3
30480444	10.1021/acs.jmedchem.8b01652	Unchecked	3
30480444	10.1021/acs.jmedchem.8b01652	Proto-oncogene tyrosine-protein kinase Src	2
30480444	10.1021/acs.jmedchem.8b01652	L929	2
30480444	10.1021/acs.jmedchem.8b01652	Mitogen-activated protein kinase 13	1
30480444	10.1021/acs.jmedchem.8b01652	Tyrosine-protein kinase Lck	1
30480444	10.1021/acs.jmedchem.8b01652	Hepatocyte growth factor receptor	1
30480444	10.1021/acs.jmedchem.8b01652	Interferon-induced, double-stranded RNA-activated protein kinase	1
30480444	10.1021/acs.jmedchem.8b01652	Tyrosine-protein kinase Mer	1
30480444	10.1021/acs.jmedchem.8b01652	Mitogen-activated protein kinase kinase kinase 10	1
30480444	10.1021/acs.jmedchem.8b01652	Proto-oncogene tyrosine-protein kinase receptor Ret	1
30480444	10.1021/acs.jmedchem.8b01652	High affinity nerve growth factor receptor	1
30480444	10.1021/acs.jmedchem.8b01652	BDNF/NT-3 growth factors receptor	1
30480444	10.1021/acs.jmedchem.8b01652	Serine/threonine-protein kinase WNK3	1
30480444	10.1021/acs.jmedchem.8b01652	Tyrosine-protein kinase Yes	1
36400288	10.1016/j.bmcl.2022.129047	Interferon-induced, double-stranded RNA-activated protein kinase	1
30480444	10.1021/acs.jmedchem.8b01652	Tyrosine-protein kinase Blk	1

Data from ChEMBL 36 via Core Engine