Compound Detail

CHEMBL1922094

APITOLISIB

🧪 Phase II

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🧪 Phase II

Cc1c(CN2CCN(C(=O)[C@H](C)O)CC2)sc2c(N3CCOCC3)nc(-c3cnc(N)nc3)nc12

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL1922094
Name	APITOLISIB
Phase	Phase II
Structure Type	MOL
InChI Key	YOVVNQKCSKSHKT-HNNXBMFYSA-N

Known Names

Apitolisib G-038390 G-038390.1 GDC-0980 GDC-0980.1 Gne-390 Rg-7422 RG7422

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

498.6

MW (Da)

0.90

ALogP

HBA

HBD

133.8

PSA (Å²)

0.52

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Single Enantiomer

Flags

Natural Product Chemical Probe

USAN Stem	-lisib
USAN Year	2013

Extended Properties

Molecular Formula	C23H30N8O3S
MW	498.61
Aromatic Rings	3
Heavy Atoms	35
NP-Likeness	-1.49

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Serine/threonine-protein kinase mTOR inhibitor	INHIBITOR	Serine/threonine-protein kinase mTOR	✓	✓
PI3-kinase class I inhibitor	INHIBITOR	PI3-kinase class I	✓	✓

Indications

Breast Neoplasms Carcinoma, Renal Cell Endometrial Neoplasms Lymphoma, Non-Hodgkin Neoplasms Prostatic Neoplasms, Castration-Resistant

Activity Summary

IC50 36 meas. best 8.32

Kd 21 meas. best 9.21

Ki 5 meas. best 8.3

EC50 1 meas. best 6.51

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform CHEMBL4005	Kd	9.21	9.21	0.6	1
Unchecked CHEMBL612545	Kd	8.7	8.7	2.0	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform CHEMBL3267	Kd	8.59	8.59	2.6	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform CHEMBL3130	Kd	8.48	8.48	3.3	1
Serine/threonine-protein kinase mTOR CHEMBL2842	Kd	8.48	8.48	3.3	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform CHEMBL3145	Kd	8.42	8.42	3.8	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform CHEMBL4005	IC50	8.32	8.3033	4.8	6
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform CHEMBL4005	Ki	8.3	8.3	5.0	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform CHEMBL3130	IC50	8.17	8.155	6.7	4
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform CHEMBL3267	IC50	7.85	7.768	14.0	5
Serine/threonine-protein kinase mTOR CHEMBL2842	Ki	7.77	7.77	17.0	3
Serine/threonine-protein kinase mTOR CHEMBL2842	IC50	7.77	7.77	17.0	2
Tyrosine-protein kinase JAK1 CHEMBL2835	Kd	7.58	7.58	26.0	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform CHEMBL3145	IC50	7.57	7.57	27.0	4
Tyrosine-protein kinase SYK CHEMBL2599	IC50	6.87	6.87	134.0	1
Mitogen-activated protein kinase kinase kinase 9 CHEMBL2872	IC50	6.63	6.63	232.0	1
Phosphatidylinositol 3-kinase catalytic subunit type 3 CHEMBL1075165	Kd	6.6	6.6	250.0	1
NON-PROTEIN TARGET CHEMBL3879801	IC50	6.59	6.59	255.0	1
PC-3 CHEMBL390	IC50	6.51	6.51	307.0	1
NON-PROTEIN TARGET CHEMBL3879801	EC50	6.51	6.51	310.0	1
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta CHEMBL5554	Kd	6.24	6.24	580.0	1
Tyrosine-protein kinase Tec CHEMBL4246	Kd	6.24	6.24	570.0	1
Unchecked CHEMBL612545	Ki	6.21	6.21	623.0	1
Tyrosine-protein kinase Fgr CHEMBL4454	IC50	6.16	6.16	697.0	1
Serine/threonine-protein kinase ULK3 CHEMBL5047	Kd	6.14	6.14	721.0	1
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta CHEMBL5554	IC50	6.1	6.1	794.0	1
Tyrosine-protein kinase ABL1 CHEMBL1862	Kd	6.09	6.09	814.0	1
Serine/threonine-protein kinase PAK 4 CHEMBL4482	Kd	6.04	6.04	904.0	1
HCT-116 CHEMBL394	IC50	5.96	5.96	1110.0	1
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha CHEMBL1075102	IC50	5.89	5.89	1300.0	1
Tyrosine-protein kinase Fer CHEMBL3982	Kd	5.83	5.83	1497.0	1
Tyrosine-protein kinase BTK CHEMBL5251	Kd	5.81	5.81	1555.0	1
MDA-MB-468 CHEMBL614335	IC50	5.78	5.78	1670.0	1
SW-620 CHEMBL612262	IC50	5.76	5.76	1720.0	1
Phosphatidylinositol 3-kinase catalytic subunit type 3 CHEMBL1075165	IC50	5.7	5.7	2000.0	1
Protein kinase C alpha type CHEMBL299	Kd	5.67	5.67	2134.0	1
SARS-CoV-2 CHEMBL4303835	IC50	5.64	5.64	2310.0	2
Serine/threonine-protein kinase 10 CHEMBL3981	Kd	5.64	5.64	2269.0	1
MDA-MB-231 CHEMBL400	IC50	5.61	5.61	2460.0	1
HCC1937 CHEMBL1075458	IC50	5.49	5.49	3210.0	1
Dual specificity mitogen-activated protein kinase kinase 5 CHEMBL4948	Kd	5.45	5.45	3576.0	1
Epidermal growth factor receptor CHEMBL203	Kd	5.31	5.31	4874.0	1
DNA-dependent protein kinase catalytic subunit CHEMBL3142	Kd	5.01	5.01	9800.0	1
STE20-like serine/threonine-protein kinase CHEMBL4202	Kd	4.99	4.99	10170.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
CL	3.0	mL.min-1.kg-1	Rattus norvegicus
CL	10.96	mL.min-1.g-1	Homo sapiens
CL	3.0	uL.min-1.(10^6cells)-1	Rattus norvegicus

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	Kd	=	0.62	nM	9.21	Binding affinity to human PI3Kalpha (R108 to N1068 residues) expressed in mammal...	28829592
Unchecked	Kd	=	2.0	nM	8.7	Binding affinity to PI3K (unknown origin) assessed as dissociation constant	38295689
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	Kd	=	2.6	nM	8.59	Binding affinity to human PI3Kgamma (S144 to A1102 residues) expressed in mammal...	28829592
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform	Kd	=	3.3	nM	8.48	Binding affinity to human PI3Kdelta (R108 to Q1044 residues) expressed in mammal...	28829592
Serine/threonine-protein kinase mTOR	Kd	=	3.3	nM	8.48	Binding affinity to human mTOR (L1382 to W2549 residues) expressed in mammalian ...	28829592
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	Kd	=	3.8	nM	8.42	Binding affinity to human PI3Kbeta (P118 to S1070 residues) expressed in mammali...	28829592
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	4.8	nM	8.32	Inhibition of PI3K subunit p110alpha assessed as formation of phosphatidylinosit...	21981714
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	5.0	nM	8.3	Inhibition of P13Kalpha (unknown origin)	36462440
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	5.0	nM	8.3	Inhibition of PI3Kalpha (unknown origin)	-
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	5.0	nM	8.3	Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate measured after ...	33740547
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Ki	=	5.0	nM	8.3	Inhibition of recombinant PI3Kalpha (unknown origin) using dioctanoylglycerol-PI...	27096040
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	5.0	nM	8.3	Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate measured after ...	38183777
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	5.0	nM	8.3	Inhibition of p110 alpha (unknown origin)	20729870
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform	IC50	=	6.7	nM	8.17	Inhibition of PI3K subunit p110delta assessed as formation of phosphatidylinosit...	21981714
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform	IC50	=	7.0	nM	8.15	Inhibition of PI3Kdelta (unknown origin)	-
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform	IC50	=	7.0	nM	8.15	Inhibition of P13Kdelta (unknown origin)	36462440
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform	IC50	=	7.0	nM	8.15	Inhibition of p110 delta (unknown origin)	20729870
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	IC50	=	14.0	nM	7.85	Inhibition of p110 gamma (unknown origin)	20729870
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	IC50	=	14.0	nM	7.85	Inhibition of P13Kgamma (unknown origin)	36462440
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	IC50	=	14.0	nM	7.85	Inhibition of PI3Kgamma (unknown origin)	-

Literature References

PubMed	DOI	Target Context	# Activities
-	10.6019/CHEMBL4495565	SARS-CoV-2	6
29191878	10.1126/science.aan4368	Unchecked	4
21981714	10.1021/jm2009327	PC-3	4
33740547	10.1016/j.ejmech.2021.113357	MDA-MB-468	3
27096040	10.1021/acsmedchemlett.6b00005	ADMET	3
21981714	10.1021/jm2009327	MCF7	3
22946614	10.1021/jm300867c	ADMET	2
23199076	10.1021/jm301389h	Mus musculus	2
-	10.6019/CHEMBL4495565	Vero C1008	2
-	10.6019/CHEMBL3301361	No relevant target	2
-	10.6019/CHEMBL4495564	Replicase polyprotein 1ab	2
-	10.6019/CHEMBL4651402	SARS-CoV-2	2
22084396	10.1158/0008-5472.can-11-1515	A2058	2
21981714	10.1021/jm2009327	Tyrosine-protein kinase SYK	2
21981714	10.1021/jm2009327	Mitogen-activated protein kinase kinase kinase 9	2
21981714	10.1021/jm2009327	Tyrosine-protein kinase Fgr	2
-	10.6019/CHEMBL3301361	ADMET	2
-	10.6019/CHEMBL4495565	ADMET	2
21981714	10.1021/jm2009327	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	2
-	10.6019/CHEMBL4808148	Histone deacetylase 6	2

Data from ChEMBL 36 via Core Engine