Compound Detail

CHEMBL3813842

PAXALISIB

🧪 Phase II

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🧪 Phase II

CC1(C)OCCn2c1nc1c(N3CCOCC3)nc(-c3cnc(N)nc3)nc12

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL3813842
Name	PAXALISIB
Phase	Phase II
Structure Type	MOL
InChI Key	LGWACEZVCMBSKW-UHFFFAOYSA-N

Known Names

G-02441729 G02441729 GDC-0084 GDC0084 Paxalisib RG 7666 Rg-7666 Sim-0395

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

382.4

MW (Da)

0.97

ALogP

HBA

HBD

117.1

PSA (Å²)

0.69

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Achiral

USAN Stem	-lisib
USAN Year	2020

Extended Properties

Molecular Formula	C18H22N8O2
MW	382.43
Aromatic Rings	3
Heavy Atoms	28
NP-Likeness	-0.99

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
PI3-kinase class I inhibitor	INHIBITOR	PI3-kinase class I	✓	✓

Indications

Breast Neoplasms Glioblastoma Central Nervous System Neoplasms Neoplasms

Activity Summary

EC50 7 meas. best 6.57

IC50 5 meas. best 8.7

Ki 3 meas. best 8.7

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform CHEMBL4005	IC50	8.7	8.7	2.0	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform CHEMBL4005	Ki	8.7	8.7	2.0	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform CHEMBL3130	IC50	8.52	8.52	3.0	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform CHEMBL3267	IC50	8.0	8.0	10.0	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform CHEMBL3145	IC50	7.34	7.34	46.0	1
Serine/threonine-protein kinase mTOR CHEMBL2842	IC50	7.16	7.16	70.0	1
Serine/threonine-protein kinase mTOR CHEMBL2842	Ki	7.16	7.16	70.0	1
mTORC1 CHEMBL4296661	Ki	7.16	7.16	70.0	1
NON-PROTEIN TARGET CHEMBL3879801	EC50	6.57	6.2314	270.0	7

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	3174.17	ng.hr.mL-1	Rattus norvegicus
AUC	17974.21	ng.hr.mL-1	Mus musculus
CL	28.0	mL.min-1.kg-1	Rattus norvegicus
CL	17.0	mL.min-1.kg-1	Mus musculus
F	77.0	%	Rattus norvegicus
F	75.0	%	Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	2.0	nM	8.7	Inhibition of P13Kalpha (unknown origin)	36462440
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Ki	=	2.0	nM	8.7	Inhibition of recombinant PI3Kalpha (unknown origin) using dioctanoylglycerol-PI...	27096040
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform	IC50	=	3.0	nM	8.52	Inhibition of P13Kdelta (unknown origin)	36462440
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	IC50	=	10.0	nM	8.0	Inhibition of P13Kgamma (unknown origin)	36462440
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	IC50	=	46.0	nM	7.34	Inhibition of P13Kbeta (unknown origin)	36462440
Serine/threonine-protein kinase mTOR	IC50	=	70.0	nM	7.16	Inhibition of mTOR (unknown origin)	36462440
Serine/threonine-protein kinase mTOR	Ki	=	70.0	nM	7.16	Inhibition of human recombinant mTOR (1360 to 2549 residues) expressed in insect...	27096040
mTORC1	Ki	=	70.0	nM	7.16	Binding affinity to mTORC1 (unknown origin) assessed as apparent inhibition cons...	38183777
NON-PROTEIN TARGET	EC50	=	270.0	nM	6.57	Antiproliferative activity against human G111 cells after 4 days by CellTitre-Gl...	27096040
NON-PROTEIN TARGET	EC50	=	400.0	nM	6.4	Antiproliferative activity against human PC3 cells after 3 days by CellTitre-Glo...	27096040
NON-PROTEIN TARGET	EC50	=	530.0	nM	6.28	Antiproliferative activity against human G96 cells after 4 days by CellTitre-Glo...	27096040
NON-PROTEIN TARGET	EC50	=	580.0	nM	6.24	Antiproliferative activity against human G112 cells after 4 days by CellTitre-Gl...	27096040
NON-PROTEIN TARGET	EC50	=	740.0	nM	6.13	Antiproliferative activity against human U87 cells after 4 days by CellTitre-Glo...	27096040
NON-PROTEIN TARGET	EC50	=	1010.0	nM	6.0	Antiproliferative activity against human SF268 cells after 4 days by CellTitre-G...	27096040
NON-PROTEIN TARGET	EC50	=	1010.0	nM	6.0	Antiproliferative activity against human G122 cells after 4 days by CellTitre-Gl...	27096040

Literature References

PubMed	DOI	Target Context	# Activities
27096040	10.1021/acsmedchemlett.6b00005	NON-PROTEIN TARGET	8
27096040	10.1021/acsmedchemlett.6b00005	Mus musculus	7
27096040	10.1021/acsmedchemlett.6b00005	ADMET	6
27096040	10.1021/acsmedchemlett.6b00005	Brain	4
27096040	10.1021/acsmedchemlett.6b00005	Rattus norvegicus	4
27096040	10.1021/acsmedchemlett.6b00005	cAMP-dependent protein kinase catalytic subunit alpha	3
27096040	10.1021/acsmedchemlett.6b00005	Tyrosine-protein kinase Lyn	2
27096040	10.1021/acsmedchemlett.6b00005	Molecular identity unknown	2
27096040	10.1021/acsmedchemlett.6b00005	Casein kinase II subunit alpha	2
27096040	10.1021/acsmedchemlett.6b00005	3-phosphoinositide-dependent protein kinase 1	2
27096040	10.1021/acsmedchemlett.6b00005	Mitogen-activated protein kinase 14	2
27096040	10.1021/acsmedchemlett.6b00005	Cyclin-dependent kinase 5/CDK5 activator 1	2
27096040	10.1021/acsmedchemlett.6b00005	Protein kinase C beta type	2
27096040	10.1021/acsmedchemlett.6b00005	Serine/threonine-protein kinase pim-1	1
38183777	10.1016/j.ejmech.2023.116109	mTORC1	1
27096040	10.1021/acsmedchemlett.6b00005	Serine/threonine-protein kinase pim-2	1
27096040	10.1021/acsmedchemlett.6b00005	Phosphatidylinositol 4-kinase alpha	1
27096040	10.1021/acsmedchemlett.6b00005	Phosphatidylinositol 3-kinase catalytic subunit type 3	1
27096040	10.1021/acsmedchemlett.6b00005	Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha	1
27096040	10.1021/acsmedchemlett.6b00005	Platelet-derived growth factor receptor beta	1

Data from ChEMBL 36 via Core Engine