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Purity: ≥98%
BKM120 (also known as NVP-BKM120, or Buparlisib) is a selective, orally bioavailable and potent Pan-class I PI3K inhibitor of p110α/β/δ/γ with IC50 of 52 nM/166 nM/116 nM/262 nM in cell-free assays, respectively. It has anticancer activity. It has diminished effectiveness against VPS34, mTOR, DNAPK, and is barely active against PI4K. A number of clinical trials involving BKM120 have been conducted for the treatment of various cancers. Cellular processes like cell proliferation, growth, survival, apoptosis, protein synthesis, and glucose metabolism are regulated by the intracellular phosphatidylinositol-3-kinase (PI3K) pathway. The 2-morpholino pyrimidine derivative's biologic characterization, BKM120, is a pan-PI3K inhibitor. NVP-BKM120 inhibits all four class I PI3K isoforms in biochemical assays with at least 50-fold selectivity over other protein kinases, according to in vitro research.
| 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 = 52 nM); p110α-E545K (IC50 = 99 nM); mTOR (IC50 = 4.6 μM)
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| ln Vitro |
Buparlisib (NVP-BKM120) exhibits 50-300 nM activity for class I PI3K’s, including the most common p110α mutants. Additionally, NVP-BKM120 is less effective against class III and class IV PI3Ks, with biochemical activity being detected at 2, 5, >5, and >25 μM for the inhibition of VPS34, mTOR, DNAPK, and PI4K, respectively[1]. Buparlisib (NVP-BKM120) induces multiple myeloma (MM) cell apoptosis in a manner that depends on both the dose and the passage of time. At concentrations ≥10 μM, buparlisib (NVP-BKM120) significantly induces apoptosis in all tested MM cell lines at 24 h (P<0.05, compared to control). If not specified otherwise, the following experiments will use ≥10 μM buparlisib (NVP-BKM120) and a 24-hour treatment period. All of the tested MM cell lines exhibit a dose-dependent growth inhibition in response to buparlisib (NVP-BKM120) treatment. Buparlisib (NVP-BKM120) IC50 varies among tested MM cells. 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 μM,. In conclusion, NVP-BKM120 treatment inhibits the growth of MM cells and causes them to die off in ways that depend on the dose and the length of time[2].
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| ln Vivo |
In A2780 xenograft tumors, oral dosing of Buparlisib (NVP-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, partial inhibition of pAKTSer473 is seen, and at doses of 30, 60, or 100 mg/kg, nearly complete inhibition is seen. Both plasma and tumor drug exposure were well correlated with the inhibition of pAKT (normalized to total AKT)[1]. Buparlisib (NVP-BKM120) (5 M per kg per day for 15 days)-treated mice had significantly lower tumor burdens than control mice, as indicated by tumor volume (P<0.05) and circulating human kappa chain level (P<0.05). Furthermore, NVP-BKM120 therapy significantly increases the survival of tumor-bearing mice (P<0.05)[2].
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| Enzyme Assay |
BKM120 is dissolved in DMSO and directly distributed into a black 384-well plate at 1.25 µL per well. To begin the reaction, add 25 µL of 10 nM PI3 kinase and 5 µg/mL 1-phosphatidylinositol (PI) in assay buffer (10 mM Tris pH 7.5, 5 mM MgCl2, 20 mM NaCl, 1 mM DTT, and 0.05% CHAPS) into each well. Next, add 25 L of 2 M ATP in assay buffer. The addition of 25 L of KinaseGlo solution stops the reaction after it has run for approximately 50% of the time required to deplete the ATP. After 5 minutes of incubation, the stopped reaction is examined to determine whether any ATP is still present.
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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. The Buparlisib (NVP-BKM120) supplied in DMSO (20 mM) is further diluted in DMSO (7.5 uL of 20 mM Buparlisib in 22.5 uL DMSO). In order to make nine concentrations, repeat the process of mixing well and adding 10 uL to 20 uL DMSO. It is then followed by the addition of the diluted Buparlisib (NVP-BKM120) solution (2 uL) to the cell medium (500 uL). Equal amounts 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: The SCID (severe combined immunodeficiency) mouse model is a female, six to eight week old mouse. One million ARP-1 or MM.1S cells suspended in 50 μL phosphate-buffered saline (PBS) are subcutaneously injected into SCID mice in the right flank. DMSO/PBS or Buparlisib (NVP-BKM120) (5 μM per kg per day) are administered intraperitoneally to mice 15 days after the development of a palpable tumor (tumor diameter ≥5 mm). Each time a blood sample is taken, tumor sizes are also measured every five days. The size of the tumor and the presence of human kappa chain or lambda chain in the bloodstream are used to assess the burden of the tumor.
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| References |
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| Molecular Formula |
C18H21F3N6O2
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|---|---|
| Molecular Weight |
410.3936
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| Exact Mass |
410.16781
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| Elemental Analysis |
C, 52.68; H, 5.16; F, 13.89; N, 20.48; O, 7.80
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| CAS # |
944396-07-0
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| Related CAS # |
Buparlisib Hydrochloride;1312445-63-8
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| Appearance |
white solid powder
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| SMILES |
NC1=NC=C(C2=NC(N3CCOCC3)=NC(N4CCOCC4)=C2)C(C(F)(F)F)=C1
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| InChi Key |
CWHUFRVAEUJCEF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H21F3N6O2/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)
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| Chemical Name |
5-[2,6-Di(4-morpholinyl)-4-pyrimidinyl]-4-(trifluoromethyl)-2-pyridinamine.
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| Synonyms |
Buparlisib; BKM120; BKM-120; BKM 120; NVPBKM120; NVP BKM120; NV- BKM120
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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 |
| 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) |
DMSO: ~82 mg/mL (199.8 mM)
Water: <1 mg/mL (slightly soluble or insoluble) Ethanol: 2 mg/mL (4.87 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.09 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 (6.09 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 (6.09 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: ≥ 2.5 mg/mL (6.09 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: ≥ 2.5 mg/mL (6.09 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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. Solubility in Formulation 6: 0.5%CMC Na:6mg/mL Solubility in Formulation 7: 2.08 mg/mL (5.07 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4367 mL | 12.1835 mL | 24.3671 mL | |
| 5 mM | 0.4873 mL | 2.4367 mL | 4.8734 mL | |
| 10 mM | 0.2437 mL | 1.2184 mL | 2.4367 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 |
| NCT04338399 | Recruiting | Drug: Buparlisib & Paclitaxel | Head and Neck Cancer | Adlai Nortye Biopharma Co., Ltd. | December 12, 2020 | Phase 3 |
| NCT04975958 | Recruiting | Drug: AN2025 Drug: AN0025 |
Locally Advanced Solid Tumor | Adlai Nortye Biopharma Co., Ltd. | September 7, 2021 | Phase 1 |
| NCT02128724 | Completed | Drug: BKM120 | Carcinoma, Non-Small-Cell Lung | University of Oxford | April 2013 | Phase 1 |
| NCT01551030 | Completed | Drug: Buparlisib | Metastatic Transitional Cell Carcinoma of the Urothelium |
Memorial Sloan Kettering Cancer Center |
March 2012 | Phase 2 |
| NCT02048787 | Completed | Drug: Buparlisib | Renal Impairment | Novartis Pharmaceuticals | March 2014 | Phase 1 |
Analysis ofbuparlisibsubstrate affinity for ABC transporters usingin vitrotransport assays.Sci Rep.2018 Jul 17;8(1):10784. |
Theimpact of P-gp and BCRP on the brain and tissue penetration of buparlisib.
Buparlisibhas excellent intracranial target engagement and oral bioavailability.Sci Rep.2018 Jul 17;8(1):10784. |
NVP-BKM120inhibits cancer cell proliferation and induces apoptosis in a CCA mouse model.Oncol Lett.2018 Aug;16(2):1627-1633. |
Growth inhibition effect ofNVP-BKM120on CCA cell lines.Oncol Lett.2018 Aug;16(2):1627-1633. |
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