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Purity: ≥98%
BKM120 HCl (also known as NVP-BKM120, or Buparlisib), the hydrochloride salt of BKM-120, is a selective and potent Pan-class I PI3K inhibitor with anticancer activity. It inhibits p110α/β/δ/γ with IC50 values of 52 nM, 166 nM, 116 nM, and 262 nM, respectively. Its effectiveness against VPS34, mTOR, DNAPK, and PI4Kβ is reduced. For the treatment of various cancers, BKM120 has been put through numerous clinical trials. The intracellular phosphatidylinositol-3-kinase (PI3K) pathway controls cellular processes such as protein synthesis, glucose metabolism, and cell growth, survival, and apoptosis. A pan-PI3K inhibitor, BKM120 is a biological characterization of the 2-morpholino pyrimidine derivative.
| Targets |
p110α (IC50 = 52 nM); p110β (IC50 = 166 nM); p110δ (IC50 = 116 nM); p110γ (IC50 = 262 nM); Vps34 (IC50 = 2.4 μM); p110α-H1047R (IC50 = 58 nM); p110α-E545K (IC50 = 99 nM); mTOR (IC50 = 4.6 μM)
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| ln Vitro |
Buparlisib (BKM120) exhibits 50-300 nM activity for class I PI3K’s, including the most common p110α mutants. Additionally, NVP-BKM120 has less potency against class III and class IV PI3K's; inhibition of VPS34, mTOR, DNAPK, and PI4K, respectively, is seen to be inhibited by 2, 5, >5, and >25 μM biochemical activity, respectively[1]. Both dose and time dependencies are present in how buparlisib (BKM120) causes apoptosis in multiple myeloma (MM) cells. Buparlisib (BKM120) significantly induces apoptosis in all tested MM cell lines after 24 hours at concentrations 10 μM (P<0.05, compares with control). If not specified otherwise, the following experiments will use 10 μM buparlisib (BKM120) and a 24-h treatment. All of the tested MM cell lines exhibit a dose-dependent growth inhibition in response to buparlisib (BKM120) treatment. Each tested MM cell has a different buparlisib (BKM120) IC50 value. ARP-1, ARK, and MM.1R have an IC50 of between 1 and 10 μM at 24 h of treatment, whereas MM.1S has an IC50 of less than <1 μM and U266 has an IC50 of between 10 and 100 M. In conclusion, buparlisib (BKM120) treatment causes MM cell growth inhibition and apoptosis in ways that depend on the dose and time[2].
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| ln Vivo |
In A2780 xenograft tumors, oral dosing of Buparlisib (BKM120) at 3, 10, 30, 60, and 100 mg/kg results in a dose dependent modulation of pAKTSer473. At doses of 3 and 10 mg/kg, pAKTSer473 is partially inhibited, and at doses of 30, 60, or 100 mg/kg, it is nearly completely inhibited. Both plasma and tumor drug exposure were well correlated with inhibition of pAKT (normalized to total AKT)[1]. Buparlisib (BKM120) (5 μM per kg per day for 15 days)-treated mice had significantly lower tumor burdens than control mice, as determined by tumor volume (P<0.05) and level of circulating human kappa chain (P<0.05). Additionally, buparlisib (BKM120) treatment significantly increases the survival of tumor-bearing mice (P<0.05)[2].
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| Enzyme Assay |
BKM120 is dissolved in DMSO and then immediately distributed at a rate of 1.25 µL per well into a black 384-well plate for the PI3K biochemical assay (ATP depletion assay). 25 µL of 10 nM PI3 kinase, 5 µg/mL 1-phosphatidylinositol (PI), and 25 µL of 2 µM ATP in assay buffer are added to each well to initiate the reaction. Assay buffer is composed of 10 mM Tris pH 7.5, 5 mM MgCl2, 20 mM NaCl, 1 mM DTT, and 0.05% CHAPS. The addition of 25 µL of KinaseGlo solution stops the reaction after it has run for approximately 50% of the ATP. The stopped reaction is allowed to continue for five minutes, after which the remaining ATP is found by luminescence.
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| Cell Assay |
A2780 cells are cultured in DMEM supplemented with 10% FBS. L-glutamine, sodium pyruvate, and antibiotics. In black-walled, clear-bottom plates, 1000 cells are plated in the same medium at a density of 100 uL per well, and the cells are then incubated for three to five hours. Buparlisib (BKM120) is diluted further into DMSO after being supplied in the 20 mM solution (7.5 uL of 20 mM NVP-BKM120 in 22.5 uL DMSO). To make nine concentrations, repeat the process (mix well, transfer 10 uL to 20 uL DMSO, etc.). Then, the cell medium (500 uL) is added, followed by the diluted Buparlisib (BKM120) solution (2 uL). Equal volumes of this solution (100 uL) are poured on top of the cells in 96-well plates, where they are then incubated at 37°C for three days before being developed with Cell Titer Glo. Luminescence reading with Trilux is used to ascertain whether cell proliferation is being inhibited[1].
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| Animal Protocol |
Mice: SCID(Six- to eight-week-old female severe combined immunodeficiency) mice are used. One million ARP-1 or MM.1S cells suspended in 50 mL of phosphate-buffered saline (PBS) are subcutaneously injected into SCID mice's right flank. Mice are administered DMSO/PBS or buparlisib (BKM120) (5 μL per kg per day) intraperitoneally for 15 days after the development of a palpable tumor (tumor diameter 5 mm). Blood samples are taken at regular intervals and tumor sizes are measured every five days. The size of the tumor and the presence of circulating human kappa chain or lambda chain are used to assess the burden of the tumor.
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| References |
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| Molecular Formula |
C₁₈H₂₂CLF₃N₆O₂
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| Molecular Weight |
446.85
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| Exact Mass |
446.1445
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| Elemental Analysis |
C, 48.38; H, 4.96; Cl, 7.93; F, 12.75; N, 18.81; O, 7.16
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| CAS # |
1312445-63-8
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| Related CAS # |
Buparlisib;944396-07-0
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| Appearance |
Solid powder
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| SMILES |
C1COCCN1C2=NC(=NC(=C2)C3=CN=C(C=C3C(F)(F)F)N)N4CCOCC4.Cl
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| InChi Key |
DGPLYAXBXJXEID-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H21F3N6O2.ClH/c19-18(20,21)13-9-15(22)23-11-12(13)14-10-16(26-1-5-28-6-2-26)25-17(24-14)27-3-7-29-8-4-27;/h9-11H,1-8H2,(H2,22,23);1H
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| Chemical Name |
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.59 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.59 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.59 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 0.5% CMC Na : 6mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2379 mL | 11.1894 mL | 22.3789 mL | |
| 5 mM | 0.4476 mL | 2.2379 mL | 4.4758 mL | |
| 10 mM | 0.2238 mL | 1.1189 mL | 2.2379 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01487265 | Completed | Drug: BKM120 and Erlotinib | Non Small Cell Lung Cancer | SCRI Development Innovations, LLC | March 2014 | Phase 2 |
| NCT01971489 | Withdrawn | Drug: Buparlisib Drug: Cisplatin |
Adult Solid Neoplasm Stage IIIA Non-Small Cell Lung Cancer |
Roswell Park Cancer Institute | September 2015 | Phase 1 |
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J Mol Med, 2011, 89(9), 877-889. |
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