Buparlisib (BKM120)
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MedKoo CAT#: 204690

CAS#: 944396-07-0 (free base)

Description: Buparlisib, also known as BKM120, is an orally bioavailable specific oral inhibitor of the pan-class I phosphatidylinositol 3-kinase (PI3K) family of lipid kinases with potential antineoplastic activity. PI3K inhibitor BKM120 specifically inhibits class I PIK3 in the PI3K/AKT kinase (or protein kinase B) signaling pathway in an ATP-competitive manner, thereby inhibiting the production of the secondary messenger phosphatidylinositol-3,4,5-trisphosphate and activation of the PI3K signaling pathway.


Chemical Structure

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Buparlisib (BKM120)
CAS# 944396-07-0 (free base)

Theoretical Analysis

MedKoo Cat#: 204690
Name: Buparlisib (BKM120)
CAS#: 944396-07-0 (free base)
Chemical Formula: C18H21F3N6O2
Exact Mass: 410.16781
Molecular Weight: 410.39
Elemental Analysis: C, 52.68; H, 5.16; F, 13.89; N, 20.48; O, 7.80

Price and Availability

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100.0mg USD 150.0 Ready to ship
200.0mg USD 250.0 Ready to ship
500.0mg USD 450.0 Ready to ship
1.0g USD 850.0 Ready to ship
2.0g USD 1450.0 Ready to ship
5.0g USD 2450.0 Ready to ship
10.0g USD 3950.0 Ready to ship
20.0g USD 6950.0 Ready to ship
50.0g USD 9950.0 2 Weeks
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Related CAS #: 944396-07-0 (free base)   1312445-63-8 (HCl)    

Synonym: NVPBKM120; NVP BKM120; NV- BKM120; BKM120; BKM-120; BKM 120; Buparlisib.

IUPAC/Chemical Name: 5-[2,6-Di(4-morpholinyl)-4-pyrimidinyl]-4-(trifluoromethyl)-2-pyridinamine.

InChi Key: CWHUFRVAEUJCEF-UHFFFAOYSA-N

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)

SMILES Code: NC1=NC=C(C2=NC(N3CCOCC3)=NC(N4CCOCC4)=C2)C(C(F)(F)F)=C1

Appearance: white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO.

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Buparlisib (BKM120; NVP-BKM120) is a pan-class I PI3K inhibitor, with IC50s of 52, 166, 116 and 262 nM for p110α, p110β, p110δ and p110γ, respectively.
In vitro activity: The results demonstrated that the treatment of KG-1 with BKM120 not only inhibited proliferative capacity by reducing DNA replication and the number of viable cells but also led to an increased percentage of cells in the G2/M phase, suggesting that the antiproliferative effects of the inhibitor are mediated, at least partially, through the induction of G2/M arrest. In an investigation of the effects of PI3K suppression on multiple myeloma cells, the inhibitory effect of pan-PI3K inhibition on the survival of both KMM-1 and RPMI 8226 cells via the induction of SIRT1-mediated G2/M arrest was also highlighted. Among examples of overactivation of malignant signaling networks, and foremost of the PI3K pathway, the c-Myc oncogene is explicitly activated and subsequently leads to cell cycle progression via the inhibition of cell cycle-related genes such as p21 and p27 cyclin-dependent kinase inhibitors. Remarkably, while BKM120-induced G2/M arrest was associated with the upregulation of p21 and p27 expression, this study could find no noticeable alteration in c-Myc mRNA levels, suggesting the probable contribution of the c-Myc oncogene with less sensitivity of leukemic cells to the PI3K inhibitors. Accordingly, investigation of the effects of the small-molecule inhibitor of c-Myc revealed that 10058-F4 reduced KG-1 cell survival and sensitized the cells to lower concentrations of either BKM120 or idelalisib, supporting the hypothesis that the c-Myc inhibitors may restore leukemic cell sensitivity to PI3K inhibitors when administered as part of combination regimens. Reference: Turk J Haematol. 2020 Sep; 37(3): 167–176. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463220/
In vivo activity: This study next used intracranial orthotopic allografts of PP (p53f/f;Ptenf/f ) GBM (glioblastoma) to examine BKM120 (also known as buparlisib; Table S1). BKM120 is currently the only pan-PI3K inhibitor with proven brain penetration and has been tested in the clinic for GBM patients. Treatment with BKM120 prolonged the median survival of PP-bearing mice slightly from 22 to 27 days (Figure 4A). While this result is statistically significant, it is unlikely to have a meaningful clinical impact. WB and IHC analyses of tumors harvested from experimental mice showed that BKM120 modestly reduced phosphorylation of both Akt and S6RP (Figures 4B and and4C),4C), suggesting that while BKM120 can cross the BBB, it cannot deeply suppress Akt-mammalian target of rapamycin (mTOR) signaling. Data are consistent with a recent clinical trial that showed that BKM120 does not effectively suppress S6RP phosphorylation despite adequate brain penetration and has limited efficacy in patients with GBM. Reference: Cell Rep. 2020 Sep 29; 32(13): 108196. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571617/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 91.0 221.74
Ethanol 82.0 199.81

Preparing Stock Solutions

The following data is based on the product molecular weight 410.39 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Sadeghi S, Esmaeili S, Pourbagheri-Sigaroodi A, Safaroghli-Azar A, Bashash D. PI3K Abrogation Using Pan-PI3K Inhibitor BKM120 Gives Rise to a Significant Anticancer Effect on AML-Derived KG-1 Cells by Inducing Apoptosis and G2/M Arrest. Turk J Haematol. 2020 Aug 28;37(3):167-176. doi: 10.4274/tjh.galenos.2020.2019.0440. Epub 2020 Mar 12. PMID: 32160736; PMCID: PMC7463220. 2. Padthaisong S, Dokduang H, Yothaisong S, Techasen A, Namwat N, Yongvanit P, Khuntikeo N, Titapun A, Sangkhamanon S, Loilome W. Inhibitory effect of NVP-BKM120 on cholangiocarcinoma cell growth. Oncol Lett. 2018 Aug;16(2):1627-1633. doi: 10.3892/ol.2018.8848. Epub 2018 May 31. PMID: 30008846; PMCID: PMC6036373. 3. Xie S, Ni J, McFaline-Figueroa JR, Wang Y, Bronson RT, Ligon KL, Wen PY, Roberts TM, Zhao JJ. Divergent Roles of PI3K Isoforms in PTEN-Deficient Glioblastomas. Cell Rep. 2020 Sep 29;32(13):108196. doi: 10.1016/j.celrep.2020.108196. PMID: 32997991; PMCID: PMC7571617. 4. Li X, Martinez-Ledesma E, Zhang C, Gao F, Zheng S, Ding J, Wu S, Nguyen N, Clifford SC, Wen PY, Ligon KL, Yung WKA, Koul D. Tie2-FGFR1 Interaction Induces Adaptive PI3K Inhibitor Resistance by Upregulating Aurora A/PLK1/CDK1 Signaling in Glioblastoma. Cancer Res. 2019 Oct 1;79(19):5088-5101. doi: 10.1158/0008-5472.CAN-19-0325. Epub 2019 Aug 15. PMID: 31416846.
In vitro protocol: 1. Sadeghi S, Esmaeili S, Pourbagheri-Sigaroodi A, Safaroghli-Azar A, Bashash D. PI3K Abrogation Using Pan-PI3K Inhibitor BKM120 Gives Rise to a Significant Anticancer Effect on AML-Derived KG-1 Cells by Inducing Apoptosis and G2/M Arrest. Turk J Haematol. 2020 Aug 28;37(3):167-176. doi: 10.4274/tjh.galenos.2020.2019.0440. Epub 2020 Mar 12. PMID: 32160736; PMCID: PMC7463220. 2. Padthaisong S, Dokduang H, Yothaisong S, Techasen A, Namwat N, Yongvanit P, Khuntikeo N, Titapun A, Sangkhamanon S, Loilome W. Inhibitory effect of NVP-BKM120 on cholangiocarcinoma cell growth. Oncol Lett. 2018 Aug;16(2):1627-1633. doi: 10.3892/ol.2018.8848. Epub 2018 May 31. PMID: 30008846; PMCID: PMC6036373.
In vivo protocol: 1. Xie S, Ni J, McFaline-Figueroa JR, Wang Y, Bronson RT, Ligon KL, Wen PY, Roberts TM, Zhao JJ. Divergent Roles of PI3K Isoforms in PTEN-Deficient Glioblastomas. Cell Rep. 2020 Sep 29;32(13):108196. doi: 10.1016/j.celrep.2020.108196. PMID: 32997991; PMCID: PMC7571617. 2. Li X, Martinez-Ledesma E, Zhang C, Gao F, Zheng S, Ding J, Wu S, Nguyen N, Clifford SC, Wen PY, Ligon KL, Yung WKA, Koul D. Tie2-FGFR1 Interaction Induces Adaptive PI3K Inhibitor Resistance by Upregulating Aurora A/PLK1/CDK1 Signaling in Glioblastoma. Cancer Res. 2019 Oct 1;79(19):5088-5101. doi: 10.1158/0008-5472.CAN-19-0325. Epub 2019 Aug 15. PMID: 31416846.

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1: Rodon J, Braña I, Siu LL, De Jonge MJ, Homji N, Mills D, Di Tomaso E, Sarr C, Trandafir L, Massacesi C, Eskens F, Bendell JC. Phase I dose-escalation and -expansion study of buparlisib (BKM120), an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. Invest New Drugs. 2014 Mar 21. [Epub ahead of print] PubMed PMID: 24652201.

2: Ando Y, Inada-Inoue M, Mitsuma A, Yoshino T, Ohtsu A, Suenaga N, Sato M, Kakizume T, Robson M, Quadt C, Doi T. Phase I dose-escalation study of buparlisib (BKM120), an oral pan-class I PI3K inhibitor, in Japanese patients with advanced solid tumors. Cancer Sci. 2014 Mar;105(3):347-53. doi: 10.1111/cas.12350. Epub 2014 Feb 13. PubMed PMID: 24405565.

3: Liang YC, Wu HG, Xue HJ, Liu Q, Shi LL, Liu T, Wu G. Effects of PI3K inhibitor NVP-BKM120 on acquired resistance to gefitinib of human lung adenocarcinoma H1975 cells. J Huazhong Univ Sci Technolog Med Sci. 2013 Dec;33(6):845-51. doi: 10.1007/s11596-013-1209-5. Epub 2013 Dec 13. PubMed PMID: 24337846.

4: Lonetti A, Antunes IL, Chiarini F, Orsini E, Buontempo F, Ricci F, Tazzari PL, Pagliaro P, Melchionda F, Pession A, Bertaina A, Locatelli F, McCubrey JA, Barata JT, Martelli AM. Activity of the pan-class I phosphoinositide 3-kinase inhibitor NVP-BKM120 in T-cell acute lymphoblastic leukemia. Leukemia. 2013 Nov 6. doi: 10.1038/leu.2013.369. [Epub ahead of print] PubMed PMID: 24310736.

5: Geisthoff UW, Nguyen HL, Hess D. Improvement in hereditary hemorrhagic telangiectasia after treatment with the phosphoinositide 3-kinase inhibitor BKM120. Ann Hematol. 2014 Apr;93(4):703-4. doi: 10.1007/s00277-013-1845-7. Epub 2013 Jul 27. PubMed PMID: 23892886.

6: Rosich L, Saborit-Villarroya I, López-Guerra M, Xargay-Torrent S, Montraveta A, Aymerich M, Villamor N, Campo E, Pérez-Galán P, Roué G, Colomer D. The phosphatidylinositol-3-kinase inhibitor NVP-BKM120 overcomes resistance signals derived from microenvironment by regulating the Akt/FoxO3a/Bim axis in chronic lymphocytic leukemia cells. Haematologica. 2013 Nov;98(11):1739-47. doi: 10.3324/haematol.2013.088849. Epub 2013 Jul 12. PubMed PMID: 23850807; PubMed Central PMCID: PMC3815175.

7: Zang C, Eucker J, Liu H, Coordes A, Lenarz M, Possinger K, Scholz CW. Inhibition of pan-class I phosphatidyl-inositol-3-kinase by NVP-BKM120 effectively blocks proliferation and induces cell death in diffuse large B-cell lymphoma. Leuk Lymphoma. 2014 Feb;55(2):425-34. doi: 10.3109/10428194.2013.806800. Epub 2013 Jul 25. PubMed PMID: 23721513.

8: Ren H, Zhao L, Li Y, Yue P, Deng X, Owonikoko TK, Chen M, Khuri FR, Sun SY. The PI3 kinase inhibitor NVP-BKM120 induces GSK3/FBXW7-dependent Mcl-1 degradation, contributing to induction of apoptosis and enhancement of TRAIL-induced apoptosis. Cancer Lett. 2013 Sep 28;338(2):229-38. doi: 10.1016/j.canlet.2013.03.032. Epub 2013 Apr 2. PubMed PMID: 23562472; PubMed Central PMCID: PMC3750077.

9: Kirstein MM, Boukouris AE, Pothiraju D, Buitrago-Molina LE, Marhenke S, Schütt J, Orlik J, Kühnel F, Hegermann J, Manns MP, Vogel A. Activity of the mTOR inhibitor RAD001, the dual mTOR and PI3-kinase inhibitor BEZ235 and the PI3-kinase inhibitor BKM120 in hepatocellular carcinoma. Liver Int. 2013 May;33(5):780-93. doi: 10.1111/liv.12126. Epub 2013 Mar 15. PubMed PMID: 23489999.

10: Amrein L, Shawi M, Grenier J, Aloyz R, Panasci L. The phosphatidylinositol-3 kinase I inhibitor BKM120 induces cell death in B-chronic lymphocytic leukemia cells in vitro. Int J Cancer. 2013 Jul;133(1):247-52. doi: 10.1002/ijc.27989. Epub 2013 Jan 15. PubMed PMID: 23238639; PubMed Central PMCID: PMC3847963.



Additional Information

Related:
944396-07-0 (free base)
1312445-63-8 (HCl).

NVP-BKM120 is a selective pan class 1 PI3 Kinase inhibitor.  It was found that NVP-BKM120 inhibited the PI3 signaling pathways, leading to different forms of cell death based on P53 statuses. Further studies are warranted to determine if NVP-BKM120 has potential as a glioma treatment. (source: http://www.ncbi.nlm.nih.gov/pubmed/22065080 ).