Compound Detail

CHEMBL2017974

BUPARLISIB

🧪 Phase III

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🧪 Phase III

Nc1cc(C(F)(F)F)c(-c2cc(N3CCOCC3)nc(N3CCOCC3)n2)cn1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL2017974
Name	BUPARLISIB
Phase	Phase III
Structure Type	MOL
InChI Key	CWHUFRVAEUJCEF-UHFFFAOYSA-N

Known Names

Bkm-120 BKM-120NX BKM120-NX Buparlisib NVP-BKM-120 NVP-BKM120

Targets

199

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

410.4

MW (Da)

1.81

ALogP

HBA

HBD

89.6

PSA (Å²)

0.82

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Achiral

USAN Stem	-lisib
USAN Year	2013

Extended Properties

Molecular Formula	C18H21F3N6O2
MW	410.40
Aromatic Rings	2
Heavy Atoms	29
NP-Likeness	-1.24

Mechanism of Action

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

Indications

Breast Neoplasms Breast Neoplasms Head and Neck Neoplasms Carcinoma, Non-Small-Cell Lung Carcinoma, Squamous Cell Endometrial Neoplasms Esophageal Neoplasms Glioblastoma Leukemia, Lymphocytic, Chronic, B-Cell Lymphoma, Mantle-Cell Melanoma Neoplasms Prostatic Neoplasms, Castration-Resistant Thymoma Thyroid Neoplasms Uterine Cervical Neoplasms Colorectal Neoplasms Gastrointestinal Stromal Tumors Kidney Diseases Leukemia

Activity Summary

IC50 182 meas. best 7.96

Kd 9 meas. best 8.46

EC50 5 meas. best 7.26

Ki 3 meas. best 7.7

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform CHEMBL4005	Kd	8.46	8.46	3.5	1
PI3-kinase p110-alpha/p85-alpha CHEMBL2111367	IC50	7.96	7.6333	11.0	3
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform CHEMBL4005	IC50	7.89	7.3259	13.0	22
Serine/threonine-protein kinase mTOR CHEMBL2842	Kd	7.72	7.72	19.0	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform CHEMBL4005	Ki	7.7	7.7	20.0	1
Unchecked CHEMBL612545	IC50	7.55	6.5569	28.0	16
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform CHEMBL3145	Kd	7.44	7.44	36.0	1
Unchecked CHEMBL612545	EC50	7.26	7.105	55.0	4
Serine/threonine-protein kinase mTOR CHEMBL2842	IC50	7.03	5.946	94.0	5
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform CHEMBL3130	IC50	6.96	6.909	110.0	10
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform CHEMBL5169092	IC50	6.93	6.93	117.0	1
PI3-kinase p110-delta/p85-alpha CHEMBL2111432	IC50	6.9	6.9	125.0	1
PI3-kinase subunit gamma/Phosphoinositide 3-kinase regulatory subunit 5 CHEMBL3430881	IC50	6.89	6.89	129.0	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform CHEMBL3267	Kd	6.89	6.89	130.0	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform CHEMBL3145	IC50	6.78	6.7167	165.0	9
Phosphatidylinositol 3-kinase catalytic subunit type 3 CHEMBL1075165	Kd	6.7	6.7	200.0	1
Serine/threonine-protein kinase mTOR CHEMBL2842	Ki	6.7	6.7	199.0	1
MCF7 CHEMBL387	IC50	6.69	5.5817	206.0	6
PI3K p110 beta/p85 alpha CHEMBL3038510	IC50	6.63	6.63	234.0	1
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform CHEMBL3267	IC50	6.59	6.4464	256.0	11
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform CHEMBL3130	Kd	6.58	6.58	260.0	1
Daoy CHEMBL612519	IC50	6.55	6.55	279.0	1
D283 Med CHEMBL614476	IC50	6.55	6.55	279.0	1
T47D CHEMBL614361	IC50	6.54	5.85	286.0	2
Phosphatidylinositol 3-kinase regulatory subunit alpha CHEMBL2506	IC50	6.51	6.51	310.0	1
A2780 CHEMBL614004	IC50	6.46	6.42	346.7	2
L1210 CHEMBL386	IC50	6.43	6.43	370.0	1
MDA-MB-453 CHEMBL614334	IC50	6.43	6.43	370.0	1
NON-PROTEIN TARGET CHEMBL3879801	IC50	6.32	6.055	480.0	2
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform CHEMBL3608198	IC50	6.28	6.28	523.0	1
A2780 CHEMBL614004	EC50	6.28	6.28	520.0	1
MV4-11 CHEMBL613835	IC50	6.25	6.195	560.0	2
U-937 CHEMBL612794	IC50	6.24	6.24	580.0	1
A549 CHEMBL392	IC50	6.19	5.694	645.6	5
NCI-N87 CHEMBL614197	IC50	6.18	6.18	660.0	1
K562 CHEMBL385	IC50	6.14	5.7333	730.0	3
Ca-Ski CHEMBL1075403	IC50	6.13	6.13	740.0	1
NB-4 CHEMBL614188	IC50	6.12	6.12	750.0	1
MOLT-4 CHEMBL614177	IC50	6.1	6.1	800.0	1
Friend leukemia cell line CHEMBL614499	IC50	6.09	6.09	810.0	1
Serine/threonine-protein kinase mTOR CHEMBL1255165	IC50	6.08	6.08	832.0	1
EL4 CHEMBL614293	IC50	6.07	6.07	860.0	1
HUVEC CHEMBL613979	IC50	6.05	6.05	886.0	1
DU-145 CHEMBL613508	IC50	6.04	5.435	910.0	4
HGC-27 CHEMBL1075463	IC50	6.0	6.0	990.0	1
Raji CHEMBL614628	IC50	6.0	6.0	990.0	1
A-431 CHEMBL614069	IC50	5.99	5.99	1030.0	1
HeLa CHEMBL399	IC50	5.93	5.4433	1170.0	3
Ramos CHEMBL614629	IC50	5.93	5.5467	1174.9	3
HL-60 CHEMBL383	IC50	5.92	5.87	1200.0	2

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	73051.2	ng.hr.mL-1	Rattus norvegicus
CL	3.0	mL.min-1.kg-1	Rattus norvegicus
CL	9.0	mL.min-1.g-1	Rattus norvegicus
CL	9.0	mL.min-1.g-1	Homo sapiens
CL	11.0	mL.min-1.kg-1	Mus musculus
CL	3.0	mL.min-1.kg-1	Rattus norvegicus
CL	7.3	mL.min-1.kg-1	Canis lupus familiaris
CL	13.0	mL.min-1.kg-1	Macaca fascicularis
CL	15.85	uL.min-1.(10^6cells)-1	Rattus norvegicus
CL	3.0	uL.min-1.(10^6cells)-1	Homo sapiens
CL	10.86	mL.min-1.kg-1	Homo sapiens
CL	151.33	mL.min-1.kg-1	Mus musculus
F	50.0	%	Rattus norvegicus
F	71.0	%	Mus musculus
F	50.0	%	Rattus norvegicus
F	100.0	%	Canis lupus familiaris
F	44.0	%	Macaca fascicularis
T1/2	1.6	hr	Mus musculus
T1/2	11.0	hr	Rattus norvegicus
T1/2	6.6	hr	Canis lupus familiaris
T1/2	3.6	hr	Macaca fascicularis

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	=	3.5	nM	8.46	Binding affinity to human PI3Kalpha (R108 to N1068 residues) expressed in mammal...	28829592
PI3-kinase p110-alpha/p85-alpha	IC50	=	11.0	nM	7.96	Inhibition of recombinant human His-tagged p85alpha/p110alpha E545K mutant expre...	30034607
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	13.0	nM	7.89	Inhibition of PI3Kalpha (unknown origin) by mobility shift assay	36272186
Serine/threonine-protein kinase mTOR	Kd	=	19.0	nM	7.72	Binding affinity to human mTOR (L1382 to W2549 residues) expressed in mammalian ...	28829592
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Ki	=	20.0	nM	7.7	Binding affinity to recombinant N-terminal His6-tagged P110alpha catalytic domai...	30359003
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	20.0	nM	7.7	Inhibition of recombinant human PI3Kalpha using PIP2 as substrate incubated for ...	31117517
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	25.0	nM	7.6	Inhibition of p110alpha H1047R mutant (unknown origin)	30034607
Unchecked	IC50	=	28.0	nM	7.55	Inhibition of PI3K p110alpha/p85 (unknown origin) using PIP2/ATP as substrate af...	27427973
PI3-kinase p110-alpha/p85-alpha	IC50	=	29.0	nM	7.54	Inhibition of recombinant human His-tagged p85alpha/p110alpha E542K mutant expre...	30034607
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	30.0	nM	7.52	Inhibition of PI3Kalpha (unknown origin)	25911625
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	30.0	nM	7.52	Inhibition of PI3Kalpha (unknown origin)	25765909
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	30.0	nM	7.52	Inhibition of PI3Kalpha (unknown origin)	-
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	30.0	nM	7.52	Inhibition of PI3Kalpha using 1-alpha-phosphatidylinositol as substrate by ATP d...	24900266
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	Kd	=	36.0	nM	7.44	Binding affinity to human PI3Kbeta (P118 to S1070 residues) expressed in mammali...	28829592
PI3-kinase p110-alpha/p85-alpha	IC50	=	40.0	nM	7.4	Inhibition of recombinant human full length N-terminal His-tagged p110alpha/p85a...	30034607
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	44.0	nM	7.36	Inhibition of PI3Kalpha (unknown origin) using L-alpha-phosphatidylinositol as s...	35500094
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	45.0	nM	7.35	Inhibition of PI3Kalpha (unknown origin)	28829592
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	50.0	nM	7.3	Inhibition of p110 alpha (unknown origin)	33650861
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	52.0	nM	7.28	Inhibition of P13Kalpha (unknown origin)	36462440
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	IC50	=	52.0	nM	7.28	Inhibition of PI3K p110alpha (unknown origin)	31581005

Literature References

PubMed	DOI	Target Context	# Activities
31846325	10.1021/acs.jmedchem.9b00622	MDA-MB-468	14
24900266	10.1021/ml200156t	Mus musculus	14
24900266	10.1021/ml200156t	Rattus norvegicus	8
33636537	10.1016/j.ejmech.2021.113268	Unchecked	8
36272186	10.1016/j.bmc.2022.117067	MV4-11	8
25177796	10.1042/bj20140889	Unchecked	6
31117517	10.1021/acs.jmedchem.9b00390	HCT-116	6
38636129	10.1016/j.ejmech.2024.116425	SiHa	6
31846325	10.1021/acs.jmedchem.9b00622	Unchecked	6
33309164	10.1016/j.ejmech.2020.113054	MDA-MB-468	6
29191878	10.1126/science.aan4368	Unchecked	5
28829592	10.1021/acs.jmedchem.7b00930	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	5
35500094	10.1021/acs.jmedchem.2c00267	ADMET	5
24900266	10.1021/ml200156t	Canis familiaris	5
27427973	10.1021/acs.jmedchem.6b00235	Unchecked	5
24900266	10.1021/ml200156t	Unchecked	5
24900266	10.1021/ml200156t	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	5
35500094	10.1021/acs.jmedchem.2c00267	Rat1	4
24900266	10.1021/ml200156t	Cynomolgus monkey	4
24900266	10.1021/ml200156t	ADMET	4

Data from ChEMBL 36 via Core Engine