Compound Detail

CHEMBL4440406

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COc1ncc(-c2ccc3ncc(-c4nnc(CCN5CCN(C)CC5)o4)n3c2)cc1NS(=O)(=O)c1ccc(F)cc1F

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL4440406
Phase	Preclinical
Structure Type	MOL
InChI Key	LSPJWTULWKYRTQ-UHFFFAOYSA-N

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Molecular Properties

610.6

MW (Da)

3.32

ALogP

HBA

HBD

131.0

PSA (Å²)

0.27

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Unknown
Availability	Unknown
Chirality	Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula	C28H28F2N8O4S
MW	610.65
Aromatic Rings	5
Heavy Atoms	43
NP-Likeness	-2.14

Activity Summary

IC50 16 meas. best 9.7

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
PI3-kinase p110-alpha/p85-alpha CHEMBL2111367	IC50	9.7	9.7	0.2	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform CHEMBL4005	IC50	9.7	9.7	0.2	1
PI3-kinase p110-delta/p85-alpha CHEMBL2111432	IC50	9.3	9.3	0.5	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform CHEMBL3130	IC50	9.3	9.3	0.5	1
PI3K p110 beta/p85 alpha CHEMBL3038510	IC50	9.24	9.24	0.6	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform CHEMBL3145	IC50	9.24	9.24	0.6	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform CHEMBL3267	IC50	8.92	8.92	1.2	2
LoVo CHEMBL614721	IC50	8.28	8.28	5.2	1
HCT-116 CHEMBL394	IC50	8.0	8.0	10.0	1
Serine/threonine-protein kinase mTOR CHEMBL2842	IC50	7.68	7.68	21.0	2
MCF7 CHEMBL387	IC50	7.4	7.4	40.0	1
HT-29 CHEMBL384	IC50	7.28	7.28	52.0	1
PC-3 CHEMBL390	IC50	7.15	7.15	71.0	1
HUVEC CHEMBL613979	IC50	4.81	4.81	15530.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	2958.0	ng.hr.mL-1	Rattus norvegicus
AUC	3965.0	ng.hr.mL-1	Rattus norvegicus
CL	5.66	mL.min-1.kg-1	Rattus norvegicus
Cmax	905.59	nM	Rattus norvegicus
F	26.8	%	Rattus norvegicus
T1/2	4.71	hr	Rattus norvegicus
T1/2	7.94	hr	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
PI3-kinase p110-alpha/p85-alpha	IC50	=	0.2	nM	9.7	Inhibition of recombinant human full-length N-terminal His-tagged p110alpha/p85a...	32069401
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	0.2	nM	9.7	Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate incubated for 1...	36586298
PI3-kinase p110-delta/p85-alpha	IC50	=	0.5	nM	9.3	Inhibition of human full-length His-tagged p110delta/p85alpha expressed in bacul...	32069401
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform	IC50	=	0.5	nM	9.3	Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate incubated for 1...	36586298
PI3K p110 beta/p85 alpha	IC50	=	0.58	nM	9.24	Inhibition of recombinant human full-length His-tagged p110beta/p85alpha express...	32069401
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	IC50	=	0.58	nM	9.24	Inhibition of PI3Kbeta (unknown origin) using PIP2 as substrate incubated for 1 ...	36586298
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	IC50	=	1.2	nM	8.92	Inhibition of recombinant human full-length His-tagged p110gamma expressed in ba...	32069401
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	IC50	=	1.2	nM	8.92	Inhibition of PI3Kgamma (unknown origin) using PIP2 as substrate incubated for 1...	36586298
LoVo	IC50	=	5.2	nM	8.28	Cytotoxicity against human LoVo cells over-expressing HER2 assessed as reduction...	32069401
HCT-116	IC50	=	10.0	nM	8.0	Cytotoxicity against human HCT116 cells harboring PIK3CA mutant assessed as redu...	32069401
Serine/threonine-protein kinase mTOR	IC50	=	21.0	nM	7.68	Inhibition of recombinant human N-terminal FLAG-tagged mTOR (1362 to end residue...	32069401
Serine/threonine-protein kinase mTOR	IC50	=	21.0	nM	7.68	Inhibition of mTOR (unknown origin) using ULight-4E-BP1 (Thr37/46) as peptide su...	36586298
MCF7	IC50	=	40.0	nM	7.4	Cytotoxicity against human MCF7 cells harboring PIK3CA mutant assessed as reduct...	32069401
HT-29	IC50	=	52.0	nM	7.28	Cytotoxicity against human HT-29 cells harboring PIK3CA mutant assessed as reduc...	32069401
PC-3	IC50	=	71.0	nM	7.15	Cytotoxicity against PTEN-deficient human PC3 cells assessed as reduction in cel...	32069401
HUVEC	IC50	=	15530.0	nM	4.81	Cytotoxicity against HUVEC assessed as reduction in cell viability	32069401

Literature References

PubMed	DOI	Target Context	# Activities
32069401	10.1021/acs.jmedchem.9b01736	ADMET	15
32069401	10.1021/acs.jmedchem.9b01736	Unchecked	9
36586298	10.1016/j.ejmech.2022.115030	ADMET	5
32069401	10.1021/acs.jmedchem.9b01736	HCT-116	4
32069401	10.1021/acs.jmedchem.9b01736	HT-29	3
32069401	10.1021/acs.jmedchem.9b01736	PI3-kinase p110-alpha/p85-alpha	2
32069401	10.1021/acs.jmedchem.9b01736	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	2
32069401	10.1021/acs.jmedchem.9b01736	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	1
32069401	10.1021/acs.jmedchem.9b01736	Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta	1
32069401	10.1021/acs.jmedchem.9b01736	Serine/threonine-protein kinase mTOR	1
32069401	10.1021/acs.jmedchem.9b01736	MCF7	1
32069401	10.1021/acs.jmedchem.9b01736	PC-3	1
32069401	10.1021/acs.jmedchem.9b01736	LoVo	1
32069401	10.1021/acs.jmedchem.9b01736	HUVEC	1
32069401	10.1021/acs.jmedchem.9b01736	PI3-kinase p110-delta/p85-alpha	1
32069401	10.1021/acs.jmedchem.9b01736	Mus musculus	1
36586298	10.1016/j.ejmech.2022.115030	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	1
36586298	10.1016/j.ejmech.2022.115030	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	1
36586298	10.1016/j.ejmech.2022.115030	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	1
36586298	10.1016/j.ejmech.2022.115030	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform	1

Data from ChEMBL 36 via Core Engine