Compound Detail

CHEMBL2204538

THPP-1

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COCCOc1nc(-c2ccc(Cl)nc2)nc2c1CN(C(=O)c1ncn3ccccc13)CC2

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL2204538
Name	THPP-1
Phase	Preclinical
Structure Type	MOL
InChI Key	JBHLOPKIPKTRSU-UHFFFAOYSA-N

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Molecular Properties

464.9

MW (Da)

3.06

ALogP

HBA

HBD

94.7

PSA (Å²)

0.32

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	C23H21ClN6O3
MW	464.91
Aromatic Rings	4
Heavy Atoms	33
NP-Likeness	-1.87

Activity Summary

Ki 23 meas. best 9.0

IC50 5 meas. best 7.31

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A CHEMBL4409	Ki	9.0	9.0	1.0	6
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A CHEMBL6140	Ki	8.89	8.89	1.3	1
Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha CHEMBL3878	Ki	7.36	7.36	44.0	2
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A CHEMBL4409	IC50	7.31	7.31	49.0	2
cGMP-specific 3',5'-cyclic phosphodiesterase CHEMBL1827	Ki	6.94	6.94	116.0	2
Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A CHEMBL2717	Ki	6.53	6.53	298.0	2
Unchecked CHEMBL612545	Ki	6.26	6.26	550.0	1
cGMP-dependent 3',5'-cyclic phosphodiesterase CHEMBL2652	Ki	5.92	5.92	1200.0	2
Sodium/nucleoside cotransporter 2 CHEMBL5780	IC50	5.79	5.79	1610.0	2
Unchecked CHEMBL612545	IC50	5.79	5.79	1610.0	1
cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A CHEMBL241	Ki	5.48	5.48	3300.0	1
Sigma intracellular receptor 2 CHEMBL4105907	Ki	5.47	5.47	3350.4	3
3',5'-cyclic-AMP phosphodiesterase 4A CHEMBL254	Ki	5.23	5.23	5900.0	2
High affinity 3',5'-cyclic-AMP phosphodiesterase 7A CHEMBL3012	Ki	4.95	4.95	11200.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
CL	7.7	mL.min-1.kg-1	Macaca mulatta
CL	3.8	mL.min-1.kg-1	Canis lupus familiaris
CL	6.0	mL.min-1.kg-1	Rattus norvegicus
CL	6.0	mL.min-1.kg-1	Rattus norvegicus
CL	3.8	mL.min-1.kg-1	Canis lupus familiaris
CL	7.7	mL.min-1.kg-1	Macaca mulatta
F	31.0	%	Macaca mulatta
F	79.0	%	Canis lupus familiaris
F	47.0	%	Rattus norvegicus
F	47.0	%	Rattus norvegicus
F	79.0	%	Canis lupus familiaris
F	31.0	%	Macaca mulatta
T1/2	1.4	hr	Macaca mulatta
T1/2	7.2	hr	Canis lupus familiaris
T1/2	1.4	hr	Rattus norvegicus
T1/2	1.4	hr	Rattus norvegicus
T1/2	7.2	hr	Canis lupus familiaris
T1/2	1.4	hr	Macaca mulatta

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A	Ki	=	1.0	nM	9.0	Inhibition of PDE10A	22892116
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A	Ki	=	0.99	nM	9.0	Fluorescence Polarization Assay: The fluorescence polarization assay for cyclic ...	-
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A	Ki	=	1.0	nM	9.0	Biochemical assay (PDE10A)	-
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A	Ki	=	0.99	nM	9.0	Affinity Biochemical interaction (Fluorescence polarization assay) EUB0000751a P...	-
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A	Ki	=	1.0	nM	9.0	Selectivity interaction (PDE panel (enzymatic activity assay)) EUB0000751a PDE10...	-
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A	Ki	=	1.0	nM	9.0	Inhibition of human fetal brain PDE10A2 expressed in human AD293 cells assessed ...	22750078
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A	Ki	=	1.3	nM	8.89	Inhibition of rat PDE10A2 assessed as inhibition of cAMP hydrolysis by fluoresce...	22750078
Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha	Ki	=	44.0	nM	7.36	Selectivity interaction (PDE panel (enzymatic activity assay)) EUB0000751a PDE6A	-
Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha	Ki	=	44.0	nM	7.36	Biochemical assay (PDE6A)	-
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A	IC50	=	49.0	nM	7.31	Affinity On-target Cellular interaction (Cell-based assay) EUB0000751a PDE10A	-
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A	IC50	=	49.0	nM	7.31	Cell assay	-
cGMP-specific 3',5'-cyclic phosphodiesterase	Ki	=	116.0	nM	6.94	Biochemical assay (PDE5A)	-
cGMP-specific 3',5'-cyclic phosphodiesterase	Ki	=	116.0	nM	6.94	Selectivity interaction (PDE panel (enzymatic activity assay)) EUB0000751a PDE5A	-
Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A	Ki	=	298.0	nM	6.53	Biochemical assay (PDE11A)	-
Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A	Ki	=	298.0	nM	6.53	Selectivity interaction (PDE panel (enzymatic activity assay)) EUB0000751a PDE11...	-
Unchecked	Ki	=	550.0	nM	6.26	Inhibition of Transporter, Adenosine at 10 µM in the Eurofins-Panlabs radioligan...	-
cGMP-dependent 3',5'-cyclic phosphodiesterase	Ki	=	1200.0	nM	5.92	Biochemical assay (PDE2A)	-
cGMP-dependent 3',5'-cyclic phosphodiesterase	Ki	=	1200.0	nM	5.92	Selectivity interaction (PDE panel (enzymatic activity assay)) EUB0000751a PDE2A	-
Sodium/nucleoside cotransporter 2	IC50	=	1610.0	nM	5.79	Selectivity interaction (Enzyme panel (Eurofins-Panlabs enzyme assay)) EUB000075...	-
Sodium/nucleoside cotransporter 2	IC50	=	1610.0	nM	5.79	Selectivity interaction (Enzyme panel (Eurofins-Panlabs radioligand binding assa...	-

Literature References

PubMed	DOI	Target Context	# Activities
22750078	10.1016/j.neuropharm.2012.06.013	ADMET	36
-	10.6019/CHEMBL4507293	Unchecked	35
-	10.6019/CHEMBL4507293	Tyrosine-protein kinase ABL1	15
22750078	10.1016/j.neuropharm.2012.06.013	Rattus norvegicus	15
22892116	10.1016/j.bmcl.2012.07.072	Rattus norvegicus	14
-	10.6019/CHEMBL4507293	Epidermal growth factor receptor	12
-	10.6019/CHEMBL5674860	Colon cancer organoid	12
-	10.6019/CHEMBL5724558	Colon cancer organoid	12
-	10.6019/CHEMBL4507293	Receptor-type tyrosine-protein kinase FLT3	11
-	10.6019/CHEMBL4689842	Fibroblast	10
22892116	10.1016/j.bmcl.2012.07.072	Unchecked	10
-	10.6019/CHEMBL4507293	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	10
-	10.6019/CHEMBL4507293	Mast/stem cell growth factor receptor Kit	9
-	10.6019/CHEMBL4689842	HEK-293T	8
-	10.6019/CHEMBL4689842	U2OS	8
-	10.6019/CHEMBL5608141	Colon cancer organoid	6
-	10.1158/2159-8290.CD-23-0050	Colon cancer organoid	5
22750078	10.1016/j.neuropharm.2012.06.013	cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A	4
-	10.6019/CHEMBL4507293	Proto-oncogene tyrosine-protein kinase receptor Ret	4
22892116	10.1016/j.bmcl.2012.07.072	Canis familiaris	4

Data from ChEMBL 36 via Core Engine