Compound Detail

CHEMBL3719135

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CC(C)n1nc(-c2cnc(N)c(OC(F)(F)F)c2)cc1[C@H]1[C@@H]2CN(C3COC3)C[C@@H]21

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL3719135
Phase	Preclinical
Structure Type	MOL
InChI Key	UHEFRVBGJORHNV-UOIKSKOESA-N

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Molecular Properties

423.4

MW (Da)

3.05

ALogP

HBA

HBD

78.4

PSA (Å²)

0.80

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Availability	Unknown
Chirality	Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula	C20H24F3N5O2
MW	423.44
Aromatic Rings	2
Heavy Atoms	30
NP-Likeness	-0.67

Activity Summary

IC50 8 meas. best 6.89

Kd 2 meas. best 7.96

Ki 2 meas. best 8.72

EC50 1 meas. best 6.24

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Mitogen-activated protein kinase kinase kinase 12 CHEMBL1908389	Ki	8.72	8.62	1.9	2
Mitogen-activated protein kinase kinase kinase 12 CHEMBL1908389	Kd	7.96	7.96	11.0	1
Mitogen-activated protein kinase kinase kinase 12 CHEMBL1908389	IC50	6.89	6.8	129.0	2
Mitogen-activated protein kinase kinase kinase 13 CHEMBL1163124	Kd	6.34	6.34	460.0	1
Mitogen-activated protein kinase kinase kinase 12 CHEMBL4295854	EC50	6.24	6.24	574.0	1
Serine/threonine-protein kinase PAK 4 CHEMBL4482	IC50	6.17	6.17	673.0	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	IC50	6.15	6.15	709.0	1
Serine/threonine-protein kinase 16 CHEMBL3938	IC50	5.82	5.82	1520.0	1
High affinity nerve growth factor receptor CHEMBL2815	IC50	5.81	5.81	1550.0	1
Mitogen-activated protein kinase kinase kinase 9 CHEMBL2872	IC50	5.23	5.23	5920.0	1
Mitogen-activated protein kinase kinase kinase 10 CHEMBL2873	IC50	5.1	5.1	7880.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
CL	8.0	mL.min-1.kg-1	Rattus norvegicus
CL	45.0	mL.min-1.kg-1	Rattus norvegicus
CL	24.6	mL.min-1.kg-1	Mus musculus
CL	186.0	mL.min-1.kg-1	Mus musculus
CL	10.0	mL.min-1.kg-1	Macaca fascicularis
CL	53.0	mL.min-1.kg-1	Macaca fascicularis
F	57.0	%	Rattus norvegicus
F	56.0	%	Rattus norvegicus
F	49.0	%	Rattus norvegicus
F	55.0	%	Rattus norvegicus
F	60.0	%	Mus musculus
F	103.0	%	Macaca fascicularis
T1/2	8.5	hr	Rattus norvegicus
T1/2	2.05	hr	Mus musculus
T1/2	7.2	hr	Macaca fascicularis
Vd	5.4	L.kg-1	Rattus norvegicus
Vd	3.6	L.kg-1	Mus musculus
Vd	5.1	L.kg-1	Macaca fascicularis

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Mitogen-activated protein kinase kinase kinase 12	Ki	=	1.9	nM	8.72	Inhibition of N-terminally GST-tagged human DLK catalytic domain (1 to 520 amino...	-
Mitogen-activated protein kinase kinase kinase 12	Ki	=	3.0	nM	8.52	Binding affinity to N-terminally GST-tagged wild type human DLK (1 to 520 residu...	28929759
Mitogen-activated protein kinase kinase kinase 12	Kd	=	11.0	nM	7.96	Binding affinity to full length wild type human DLK (M1 to P859 residues) expres...	28929759
Mitogen-activated protein kinase kinase kinase 12	IC50	=	129.0	nM	6.89	Inhibition of doxycycline inducible human DLK transfected in HEK293 cells assess...	28929759
Mitogen-activated protein kinase kinase kinase 12	IC50	=	195.0	nM	6.71	Inhibition of doxycycline inducible human DLK transfected in HEK293 cells assess...	28929759
Mitogen-activated protein kinase kinase kinase 13	Kd	=	460.0	nM	6.34	Binding affinity to full length wild type human LZK (M1 to W966 residues) expres...	28929759
Mitogen-activated protein kinase kinase kinase 12	EC50	=	574.0	nM	6.24	Inhibition of DLK in CD-1 mouse DRG neuron assessed as axonal protection pre-inc...	28929759
Serine/threonine-protein kinase PAK 4	IC50	=	673.0	nM	6.17	Inhibition of recombinant GST-tagged human PAK4 catalytic domain expressed in ba...	28929759
Receptor-type tyrosine-protein kinase FLT3	IC50	=	709.0	nM	6.15	Inhibition of recombinant His-tagged human FLT3 cytoplasmic domain expressed in ...	28929759
Serine/threonine-protein kinase 16	IC50	=	1520.0	nM	5.82	Inhibition of recombinant full length His-tagged human STK16 expressed in baculo...	28929759
High affinity nerve growth factor receptor	IC50	=	1550.0	nM	5.81	Inhibition of recombinant His-tagged human TrkA cytoplasmic domain (441 to 796 r...	28929759
Mitogen-activated protein kinase kinase kinase 9	IC50	=	5920.0	nM	5.23	Inhibition of recombinant human GST-tagged MLK1 expressed in baculovirus express...	28929759
Mitogen-activated protein kinase kinase kinase 10	IC50	=	7880.0	nM	5.1	Inhibition of recombinant human full length GST-tagged MLK2 expressed in baculov...	28929759

Literature References

PubMed	DOI	Target Context	# Activities
28929759	10.1021/acs.jmedchem.7b00843	Rattus norvegicus	51
28929759	10.1021/acs.jmedchem.7b00843	ADMET	15
28929759	10.1021/acs.jmedchem.7b00843	Unchecked	10
28929759	10.1021/acs.jmedchem.7b00843	Mus musculus	10
28929759	10.1021/acs.jmedchem.7b00843	Mitogen-activated protein kinase kinase kinase 12	6
-	10.6019/CHEMBL5303304	Fibroblast	6
28929759	10.1021/acs.jmedchem.7b00843	Cynomolgus monkey	5
-	10.6019/CHEMBL5303304	U2OS	4
28929759	10.1021/acs.jmedchem.7b00843	Voltage-gated inwardly rectifying potassium channel KCNH2	3
28929759	10.1021/acs.jmedchem.7b00843	Receptor-type tyrosine-protein kinase FLT3	2
28929759	10.1021/acs.jmedchem.7b00843	High affinity nerve growth factor receptor	2
28929759	10.1021/acs.jmedchem.7b00843	Serine/threonine-protein kinase 16	2
28929759	10.1021/acs.jmedchem.7b00843	Serine/threonine-protein kinase PAK 4	2
28929759	10.1021/acs.jmedchem.7b00843	Epidermal growth factor receptor	2
28929759	10.1021/acs.jmedchem.7b00843	Mitogen-activated protein kinase 8	2
28929759	10.1021/acs.jmedchem.7b00843	Mitogen-activated protein kinase kinase kinase 9	2
28929759	10.1021/acs.jmedchem.7b00843	Mitogen-activated protein kinase kinase kinase 10	2
28929759	10.1021/acs.jmedchem.7b00843	Mitogen-activated protein kinase 9	2
28929759	10.1021/acs.jmedchem.7b00843	Mitogen-activated protein kinase 10	2
28929759	10.1021/acs.jmedchem.7b00843	DNA-dependent protein kinase catalytic subunit	1

Data from ChEMBL 36 via Core Engine