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BKM120 (NVP-BKM120, Buparlisib)

Catalog No.S2247

BKM120 is a selective PI3K inhibitor of p110α/β/δ/γ with IC50 of 52 nM/166 nM/116 nM/262 nM, respectively. Reduced potency against VPS34, mTOR, DNAPK, with little activity to PI4Kβ. Phase 2.

: Selleck USA Tel: +1-832-582-8158[email protected]

BKM120 (NVP-BKM120, Buparlisib) Chemical Structure
Molecular Weight: 410.39

Validation & Quality Control

Customer Reviews(3) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

BKM120 (NVP-BKM120, Buparlisib) is available in the following compound libraries:

Inhibitor Library Kinase Inhibitor Library Bioactive Compound Library Cambridge Cancer Compound Library

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Product Information

Inhibition Profile
Inhibition Profile
BKM120 is a selective PI3K inhibitor of p110α/β/δ/γ with IC50 of 52 nM/166 nM/116 nM/262 nM, respectively. Reduced potency against VPS34, mTOR, DNAPK, with little activity to PI4Kβ. Phase 2.
Matthew T. Burger, et al. ACS Med. Chem. Lett., 2011, 2(10), 774–779

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Research Area
Research Area
BKM120 (NVP-BKM120, Buparlisib) Mechanism
BKM120 (NVP-BKM120, Buparlisib) Mechanism
The receptor-regulated class I PI3K are heterodimeric enzymes, consisting of a 110-kDa catalytic subunit and a regulatory subunit. Different from p110α, -β, and -δ isoforms, the p110γ isoform tightly binds to the p101 regulatory subunit. The p101 structure indicates that an N-terminal domain mediates heterodimerization with the p110γ subunit, and a C-terminal interaction domain mediates the binding to Gβγ complexes. ^[1] The ATP binding site of PI3K-gamma catalytic domain is located in a cleft between the N- and the C-terminal lobes of the catalytic domain.
BKM120 is a 2,6-dimorpholino pyrimidine derivative. The crystal structure indicates that BKM120 binds in the ATP-binding site of PI3K-gamma kinase domain. Specifically, 2-morpholino group makes an interaction via the hydrogen bond from the morpholine oxygenoxygen to the backbone amino group of Val882. The exocyclic nitrogen in the 6-position pyridyl substituent as a donor also forms two bonds to Asp841 and Asp964 in the catalytic region. In addition, a water molecule makes a hydrogen bond bridge between Tyr836 and Asp810, which acts as a hydrogen bond acceptor to interact with the 6-pyridyl endocyclic nitrogen. The binding mode results in greater affinity of PI3K enzyme for BKM120 than ATP. ^[2]
References
[1] Voigt P, et al. J Biol Chem. 2005, 280(6), 5121-5127.
[2] Maira SM, et al. Mol Cancer Ther. 2012, 11(2), 317-328.
Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Cat.No.	Product Name	Solubility (25°C)
S1009	BEZ235 (NVP-BEZ235, Dactolisib)	<1 mg/mL	1 mg/mL	<1 mg/mL
S1065	GDC-0941	<1 mg/mL	44 mg/mL	<1 mg/mL
S1105	LY294002	<1 mg/mL	36 mg/mL	21 mg/mL
S2226	CAL-101 (Idelalisib, GS-1101)	<1 mg/mL	83 mg/mL	35 mg/mL
S2247	BKM120 (NVP-BKM120, Buparlisib)	<1 mg/mL	82 mg/mL	2 mg/mL
S1038	PI-103	<1 mg/mL	24 mg/mL	<1 mg/mL
S2638	NU7441 (KU-57788)	<1 mg/mL	3 mg/mL	<1 mg/mL
S1169	TGX-221	<1 mg/mL	12 mg/mL	<1 mg/mL
S1268	IC-87114	<1 mg/mL	0.66 mg/mL	<1 mg/mL
S2758	Wortmannin	<1 mg/mL	86 mg/mL	<1 mg/mL
S1118	XL147	<1 mg/mL	3 mg/mL	<1 mg/mL
S1072	ZSTK474	<1 mg/mL	21 mg/mL	<1 mg/mL
S2814	BYL719	<1 mg/mL	88 mg/mL	2 mg/mL
S1410	AS-605240	<1 mg/mL	0.4 mg/mL	<1 mg/mL
S1205	PIK-75	<1 mg/mL	3 mg/mL	<1 mg/mL
S2767	3-Methyladenine (3-MA)	<1 mg/mL	4 mg/mL	4 mg/mL
S2636	A66	<1 mg/mL	79 mg/mL	1 mg/mL
S1523	SAR245409 (XL765)	<1 mg/mL	12 mg/mL	<1 mg/mL
S1489	PIK-93	<1 mg/mL	78 mg/mL	<1 mg/mL
S2658	GSK2126458 (GSK458)	<1 mg/mL	100 mg/mL	<1 mg/mL
S1187	PIK-90	<1 mg/mL	0.28 mg/mL	<1 mg/mL
S1462	AZD6482	<1 mg/mL	82 mg/mL	10 mg/mL
S2743	PF-04691502	<1 mg/mL	14 mg/mL	<1 mg/mL
S2696	GDC-0980 (RG7422)	<1 mg/mL	20 mg/mL	<1 mg/mL
S1360	GSK1059615	<1 mg/mL	2 mg/mL	<1 mg/mL
S7028	IPI-145 (INK1197)	<1 mg/mL	84 mg/mL	<1 mg/mL
S2628	PF-05212384 (PKI-587)	<1 mg/mL	2 mg/mL	<1 mg/mL
S1352	TG100-115	<1 mg/mL	9 mg/mL	<1 mg/mL
S2671	AS-252424	<1 mg/mL	61 mg/mL	<1 mg/mL
S2749	BGT226 (NVP-BGT226)	<1 mg/mL	30 mg/mL	<1 mg/mL
S2759	CUDC-907	<1 mg/mL	102 mg/mL	<1 mg/mL
S2227	PIK-294	<1 mg/mL	98 mg/mL	<1 mg/mL
S2681	AS-604850	<1 mg/mL	57 mg/mL	5 mg/mL
S8002	GSK2636771	<1 mg/mL	28 mg/mL	<1 mg/mL
S2802	BAY 80-6946 (Copanlisib)	0.002 mg/mL	0.002 mg/mL	0.01 mg/mL
S1219	YM201636	<1 mg/mL	35 mg/mL	<1 mg/mL
S2699	CH5132799	<1 mg/mL	12 mg/mL	<1 mg/mL
S2682	CAY10505	<1 mg/mL	58 mg/mL	<1 mg/mL
S2207	PIK-293	<1 mg/mL	80 mg/mL	<1 mg/mL
S2739	PKI-402	<1 mg/mL	0.4 mg/mL	<1 mg/mL
S2870	TG100713	<1 mg/mL	2 mg/mL	<1 mg/mL
S7016	VS-5584 (SB2343)	<1 mg/mL	71 mg/mL	3 mg/mL
S7018	CZC24832	<1 mg/mL	5 mg/mL	<1 mg/mL
S7356	HS-173	<1 mg/mL	84 mg/mL	<1 mg/mL

Product Description

Biological Activity Protocol Clinical Trial Information Chemical Information Customer Reviews Product Citations Tech Support & FAQs

Biological Activity

Description	BKM120 is a selective PI3K inhibitor of p110α/β/δ/γ with IC50 of 52 nM/166 nM/116 nM/262 nM, respectively. Reduced potency against VPS34, mTOR, DNAPK, with little activity to PI4Kβ. Phase 2.
Targets	p110α	p110δ	p110β	p110γ	Vps34	View More
IC50	52 nM ^[1]	116 nM ^[1]	166 nM ^[1]	262 nM ^[1]	2.4 μM ^[1]	View More
In vitro	BKM120 is not sensitive to Class III and Class IV PI3K's or PI4K. NVP-BKM120 shows great antiproliferation activity to PI3K deregulated cell lines including A2780, U87MG, MCF7 and DU145 with GI50 of 0.1-0.7 nM. ^[1] BKM120 induces multiple myeloma cells (ARP1, ARK, MM.1S, MM1.R and U266) apoptosis, which results in increased G1-phase cells and decreased S-phase cells. BKM120 induced CD138+ primary MM cell apoptosis and has significant lower cytotoxicity toward CD138− stromal cells. BKM120 exposure could cause upregulation of BimS and downregulation of XIAP. ^[2] BKM120 demonstrates antiproliferative activity in human gastric cancer cell lines by decreasing mTOR downstream signaling. BKM120 could increase either p-ERK or p-STAT3 in KRAS mutant gastric cancer cells. Combination with STAT3 blockade, BKM120 shows a synergism in cells harboring mutated KRAS by inducing apoptosis, but not in KRAS wild-type cells. ^[3] A recent study shows that BKM120 shows differential forms of cell death on the basis of p53 status of the cells with p53 wild-type cells undergoing apoptotic cell death and p53 mutant/deleted cells having a mitotic catastrophe cell death. BKM120 mediates mitotic catastrophe mainly through Aurora B kinase. ^[4]
In vivo	BKM120 completely inhibits pAktser473 in A2780 xenograft tumors at doses of 30, 60, or 100 mg/kg, respectively. BKM120 also shows antitumor activity against U87MG glioma model at doses of 30 and 60 mg/kg. ^[1] BKM120 treatment results in significantly reduced tumor volume and level of circulating human kappa chain at 5 μM/kg/day−1in ARP1 SCID mouse model, with prolonged survival. ^[2]
Features

Protocol(Only for Reference)

Kinase Assay: ^[1]

PI3K biochemical assay (ATP depletion assay)	BKM120 is dissolved in DMSO and directly distributed into a black 384-well plate at 1.25 µL per well. To start the reaction, 25 µL of 10 nM PI3 kinase and 5 µg/mL 1-α-phosphatidylinositol (PI) in assay buffer (10 mM Tris pH 7.5, 5 mM MgCl₂, 20 mM NaCl, 1 mM DTT and 0.05% CHAPS) are added into each well followed by 25 µL of 2 µM ATP in assay buffer. The reaction is performed until approx 50% of the ATP is depleted and then stopped by the addition of 25 µL of KinaseGlo solution. The stopped reaction is incubated for 5 minutes and the remaining ATP is then detected via luminescence.
PI3K biochemical assay (filter binding assay)	50 µL/well of a 1:1 mixture of 100 µL/mL L-α-phosphatidylinositol and L-α-phosphatidylserine dissolved in chloroform:ethanol (2.2:7.8) is pipetted into 96-well MaxiSorp^TM plates. The solvents are evaporated at room temperature and plates are washed with Tris-buffered saline (TBS, pH7.4). PI3Kα is incubated for 60 min at room temperature in coated plates in 50 µL medium containing [γ³³P]-ATP (~6 kBq/well), 0.5 µM ATP (or higher), 5 mM MgCl2, 150 mM NaCl, 25 mM Tris-HCl pH7.4, and 1% DMSO. The reaction is started by adding PI3Kα (0.4 µg/ml, <2 nM) and stopped by adding 50 µL of 50 mM EDTA. Plates are washed twice with TBS and dried; 100 µL/well MicroScint^TM PS is added, and bound radioactivity is determined using a TopCount^TM counter.

PI3K biochemical assay (ATP depletion assay)

BKM120 is dissolved in DMSO and directly distributed into a black 384-well plate at 1.25 µL per well. To start the reaction, 25 µL of 10 nM PI3 kinase and 5 µg/mL 1-α-phosphatidylinositol (PI) in assay buffer (10 mM Tris pH 7.5, 5 mM MgCl₂, 20 mM NaCl, 1 mM DTT and 0.05% CHAPS) are added into each well followed by 25 µL of 2 µM ATP in assay buffer. The reaction is performed until approx 50% of the ATP is depleted and then stopped by the addition of 25 µL of KinaseGlo solution. The stopped reaction is incubated for 5 minutes and the remaining ATP is then detected via luminescence.

PI3K biochemical assay (filter binding assay)

50 µL/well of a 1:1 mixture of 100 µL/mL L-α-phosphatidylinositol and L-α-phosphatidylserine dissolved in chloroform:ethanol (2.2:7.8) is pipetted into 96-well MaxiSorp^TM plates. The solvents are evaporated at room temperature and plates are washed with Tris-buffered saline (TBS, pH7.4). PI3Kα is incubated for 60 min at room temperature in coated plates in 50 µL medium containing [γ³³P]-ATP (~6 kBq/well), 0.5 µM ATP (or higher), 5 mM MgCl2, 150 mM NaCl, 25 mM Tris-HCl pH7.4, and 1% DMSO. The reaction is started by adding PI3Kα (0.4 µg/ml, <2 nM) and stopped by adding 50 µL of 50 mM EDTA. Plates are washed twice with TBS and dried; 100 µL/well MicroScint^TM PS is added, and bound radioactivity is determined using a TopCount^TM counter.

Cell Assay: ^[1]

Cell lines	A2780 cells.
Concentrations	0-6.6 μM
Incubation Time	3 days.
Method	A2780 cells are cultured in DMEM supplemented with 10% FBS, L-glutamine, sodium pyruvate, and antibiotics. Cells are plated in the same medium at a density of 10³ cells per well, 100 μL per well into black-walled-clear-bottom plates and incubated for 3-5 hours. BKM120 supplied in DMSO (20 mM) is diluted. The diluted BKM120 solution (2 μL), is then added to cell medium (500 μL) cell medium (concentration from 0-6.6 μM). Equal volumes of this solution (100 μL) are added to the cells in 96 well plates and incubated at 37 °C for 3 days and developed using Cell Titer Glo. Inhibition of cell proliferation is determined by luminescence read using Trilux.

Animal Study: ^[1]

Animal Models	U87MG and A2780 xenografts are established in female nu/nu mice.
Formulation	In 15% Captisol.
Dosages	~60 mg/kg.
Administration	Dosed orally daily (q.d.).
Solubility	15% Captisol, pH 4, 6 mg/mL
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

References

[1] Burger MT, et al. ACS Med Chem Lett, 2011, 2 (10), 774–779.

[2] Zheng Y, et al. J Mol Med (Berl), 2011 Dec 30.

view more

Clinical Trial Information( data from http://clinicaltrials.gov)

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Start Date	Phases
NCT02113878	Not yet recruiting	Carcinoma, Squamous Cell of Head and Neck\|HPV Positive Oropharyngeal Squamous Cell Carcinoma\|Hypopharyngeal Cancer\|Early Invasive Cervical Squamous Cell Carcinoma\|Carcinoma of Larynx\|Cancer of Nasopharynx	Dana-Farber Cancer Institute\|Novartis Pharmaceuticals	2014-04	Phase 1
NCT02000882	Not yet recruiting	Triple Negative Breast Cancer\|Brain Metastases\|Breast Cancer	US Oncology Research\|Novartis Pharmaceuticals	2014-04	Phase 2
NCT02035124	Recruiting	Advanced Prostate Cancer	SCRI Development Innovations, LLC\|Novartis	2014-04	Phase 2
NCT02058381	Recruiting	Pre-menopausal Breast Cancer\|PI3K Pathway Inhibition	Novartis\|Novartis Pharmaceuticals	2014-05	Phase 2
NCT01487265	Recruiting	Non Small Cell Lung Cancer	SCRI Development Innovations, LLC\|Novartis	2014-05	Phase 2

Chemical Information

Download BKM120 (NVP-BKM120, Buparlisib) SDF

Molecular Weight (MW)	410.39
Formula	C₁₈H₂₁F₃N₆O₂
CAS No.	944396-07-0

Storage	3 years -20℃Powder
Storage	6 months-80℃in DMSO
Synonyms

Solubility (25°C) *	In vitro	DMSO	82 mg/mL (199 mM)
		Water	<1 mg/mL (<1 mM)
		Ethanol	2 mg/mL (4 mM)
	In vivo	15% Captisol, pH 4	6 mg/mL
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Name	5-(2,6-dimorpholinopyrimidin-4-yl)-4-(trifluoromethyl)pyridin-2-amine

Molarity Calculator Dilution Calculator Molecular Weight Calculator

Research Area

Customer Reviews (3)

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Rating

Source

One customer. BKM120 (NVP-BKM120, Buparlisib) purchased from Selleck

Method

Cell growth inhibition assay

Cell Lines

Melanoma cell lines

Concentrations

0.00000512-10 μM

Incubation Time

72 h

Results

BKM120 treatment inhibited Melanoma cells growth in a does-dependent manner.

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Rating

Source

Dr. Zhang of Tianjin Medical University. BKM120 (NVP-BKM120, Buparlisib) purchased from Selleck

Method

Western blot

Cell Lines

A549 cells

Concentrations

0-10 μM

Incubation Time

3 h

Results

BKM120 treatment resulted in a reduction of Akt-308 phosphorylation in A549 cells.

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Rating

Source

Dr. Pilar Eroles of INCLIVA Biomedical Research Institute.. BKM120 (NVP-BKM120, Buparlisib) purchased from Selleck

Method

MTT assay

Cell Lines

JIMT-1 cells

Concentrations

1-1000 nM

Incubation Time

48 h

Results

JIMT-1 cells were seeded in 96 well plates (8x10<SUP>3</SUP>cells per well) andtreated with medium containing DMSO as a control and inhibitor BKM-120 (1nM, 5nM, 10nM, 50nM, 100nM, 500nM, 1000nM). Cell growth was measured after 48 hours by MTT assay.Results are expressed as a percent over DMSO control.

Product Citations (10)

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Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

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BKM120 (NVP-BKM120, Buparlisib)