Buparlisib  (Synonyms: BKM120; NVP-BKM120)

Buparlisib (BKM120; NVP-BKM120) is a pan-class I PI3K inhibitor, with blood-brain barrier permeability. Buparlisib has IC₅₀s of 52, 166, 116 and 262 nM for p110α, p110β, p110δ and p110γ, respectively^{[1][2][3][4][5]}.

Buparlisib (NVP-BKM120) exhibits activity of 50–300 nM against class I PI3K (including the most common p110α mutant). In addition, NVP-BKM120 shows lower potency against class III and IV PI3K, with biochemical activities of 2, 5, >5 and >25 μM observed, respectively, for the inhibition of VPS34, mTOR, DNAPK and PI4K^[1].
Buparlisib (≥10 μM, 24 h) induces apoptosis in multiple myeloma (MM) cells in a dose- and time-dependent manner^[1].
Buparlisib (10 μM, 24 h) causes dose-dependent growth inhibition in all tested MM cell lines, with IC₅₀ values ??between 1 and 10 μM for ARP-1, ARK, and MM.1R, while the IC50 value for MM.1S was <1 μM and for U266 it was between 10 and 100 μM^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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 pAKT^Ser473. Partial inhibition of pAKT^Ser473 is observed at 3 and 10 mg/kg, and near complete inhibition is observed at doses of 30, 60, or 100 mg/kg, respectively. Inhibition of pAKT (normalized to total AKT) tracked well with both plasma and tumor drug exposure^[1].
Mice receiving Buparlisib (NVP-BKM120) (5 μM per kg per day for 15 days) treatment has significantly smaller tumor burdens as compare with control mice, which are measured as tumor volume (P<0.05) and level of circulating human kappa chain. In addition, NVP-BKM120 treatment significantly prolongs the survival of tumor-bearing mice (P<0.05)^[2].
Buparlisib has an excellent brain penetration that is unaffected by efflux transporters at the blood-brain barrier^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

410.39

C₁₈H₂₁F₃N₆O₂

944396-07-0

Solid

White to off-white

FC(F)(C1=C(C2=CC(N3CCOCC3)=NC(N4CCOCC4)=N2)C=NC(N)=C1)F

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

• [1]. Burger MT, et al. Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer. ACS Med Chem Lett. 2011 Aug 26;2(10):774-9.  [Content Brief]

  [2]. Zheng Y, et al. Novel phosphatidylinositol 3-kinase inhibitor NVP-BKM120 induces apoptosis in myeloma cells and shows synergistic anti-myeloma activity. J Mol Med (Berl). 2012 Jun;90(6):695-706.  [Content Brief]

  [3]. Ni J, et al. Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. Nat Med. 2016 Jul;22(7):723-6.  [Content Brief]

  [4]. Liu H, et al. Identifying and Targeting Sporadic Oncogenic Genetic Aberrations in Mouse Models of Triple Negative Breast Cancer. Cancer Discov. 2018 Mar;8(3):354-369.  [Content Brief]

  [5]. de Gooijer MC, et al. Buparlisib is a brain penetrable pan-PI3K inhibitor. Sci Rep. 2018 Jul 17;8(1):10784.  [Content Brief]