Alpelisib
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MedKoo CAT#: 204780

CAS#: 1217486-61-7

Description: Alpelisib, also known as BLY719, is an orally bioavailable phosphatidylinositol 3-kinase (PI3K) inhibitor with potential antineoplastic activity. Alpelisib is equipotent against both wild type and several mutant isoforms (IC50s = 4.0-4.8 nM). eCollection 2020. Navitoclax combined with Alpelisib effectively inhibits Merkel cell carcinoma cell growth in vitro. Alpelisib Plus Letrozole Shows Promise After CDK 4/6 Inhibitor Therapy in PIK3CA-Mutated HR+/HER2- Advanced Breast Cancer.


Chemical Structure

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Alpelisib
CAS# 1217486-61-7

Theoretical Analysis

MedKoo Cat#: 204780
Name: Alpelisib
CAS#: 1217486-61-7
Chemical Formula: C19H22F3N5O2S
Exact Mass: 441.14463
Molecular Weight: 441.47
Elemental Analysis: C, 51.69; H, 5.02; F, 12.91; N, 15.86; O, 7.25; S, 7.26

Price and Availability

Size Price Availability Quantity
10.0mg USD 90.0 Ready to ship
25.0mg USD 150.0 Ready to ship
50.0mg USD 250.0 Ready to ship
100.0mg USD 450.0 Ready to ship
200.0mg USD 750.0 Ready to ship
500.0mg USD 1450.0 Ready to ship
1.0g USD 2650.0 Ready to ship
2.0g USD 4750.0 Inquiry
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Synonym: NVP-BYL719; NVP-BYL-719; NVP-BYL 719; BYL719; BYL-719; BYL 719; Alpelisib

IUPAC/Chemical Name: (S)-N1-(4-methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)thiazol-2-yl)pyrrolidine-1,2-dicarboxamide.

InChi Key: STUWGJZDJHPWGZ-LBPRGKRZSA-N

InChi Code: InChI=1S/C19H22F3N5O2S/c1-10-14(11-6-7-24-13(9-11)18(2,3)19(20,21)22)30-16(25-10)26-17(29)27-8-4-5-12(27)15(23)28/h6-7,9,12H,4-5,8H2,1-3H3,(H2,23,28)(H,25,26,29)/t12-/m0/s1

SMILES Code: O=C(N1[C@H](C(N)=O)CCC1)NC2=NC(C)=C(C3=CC(C(C)(C)C(F)(F)F)=NC=C3)S2

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: Alpelisib (BYL-719) is a PI3Kα inhibitor with IC50 of 5 nM in a cell-free assay.
In vitro activity: Whether the effect of alpelisib on the cytoskeletal and vesicular defects observed in mPTCs (mouse proximal tubule cells) resulted in changes in the endocytic uptake capacity was assessed. To differentiate the effect of alpelisib on binding and/or internalization of the ligand, mPTCs were first incubated with labeled bovine serum albumin (BSA), to induce binding of the probe with the endocytic receptors, and then incubated with growth medium, to follow the internalization of albumin (Figure 5a). Treatment with alpelisib rescued both the binding and the uptake of albumin in the OcrlY/− cells, with a 50% overall rescue of endocytic uptake (Figure 5b and c). Reference: Kidney Int. 2020 Oct;98(4):883-896. https://pubmed.ncbi.nlm.nih.gov/32919786/
In vivo activity: The potential therapeutic effect of alpelisib on PT (proximal tubule) dysfunction was tested in vivo. Ocrl mice were administered with either vehicle or alpelisib (50 mg/kg body weight per day) by oral gavage for 6 weeks (Figure 6a). Alpelisib treatment led to a significant increase in glycosuria in both Ocrl Y/+ and Ocrl Y/− mice, which could be considered as a biomarker for drug dosing (Supplementary Table S1). After 6 weeks of alpelisib treatment, the OcrlY/− mice displayed a significant reduction in the urinary excretion of the LMW proteins CC16 (−34%) and albumin (−38%), compared with vehicle-treated controls (Figure 6b and c), whereas volume of urine and other parameters were unaffected (Supplementary Table S1). Reference: Kidney Int. 2020 Oct;98(4):883-896. https://pubmed.ncbi.nlm.nih.gov/32919786/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 30.0 67.95
DMSO 67.11 152.01
DMSO:PBS (pH 7.2) (1:1) 0.5 1.13
Ethanol 1.5 3.4

Preparing Stock Solutions

The following data is based on the product molecular weight 441.47 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. Berquez M, Gadsby JR, Festa BP, Butler R, Jackson SP, Berno V, Luciani A, Devuyst O, Gallop JL. The phosphoinositide 3-kinase inhibitor alpelisib restores actin organization and improves proximal tubule dysfunction in vitro and in a mouse model of Lowe syndrome and Dent disease. Kidney Int. 2020 Oct;98(4):883-896. doi: 10.1016/j.kint.2020.05.040. Epub 2020 Sep 9. PMID: 32919786; PMCID: PMC7550850. 2. Keam B, Kim S, Ahn YO, Kim TM, Lee SH, Kim DW, Heo DS. In vitro anticancer activity of PI3K alpha selective inhibitor BYL719 in head and neck cancer. Anticancer Res. 2015 Jan;35(1):175-82. PMID: 25550549.
In vitro protocol: 1. Berquez M, Gadsby JR, Festa BP, Butler R, Jackson SP, Berno V, Luciani A, Devuyst O, Gallop JL. The phosphoinositide 3-kinase inhibitor alpelisib restores actin organization and improves proximal tubule dysfunction in vitro and in a mouse model of Lowe syndrome and Dent disease. Kidney Int. 2020 Oct;98(4):883-896. doi: 10.1016/j.kint.2020.05.040. Epub 2020 Sep 9. PMID: 32919786; PMCID: PMC7550850. 2. Keam B, Kim S, Ahn YO, Kim TM, Lee SH, Kim DW, Heo DS. In vitro anticancer activity of PI3K alpha selective inhibitor BYL719 in head and neck cancer. Anticancer Res. 2015 Jan;35(1):175-82. PMID: 25550549.
In vivo protocol: 1. Berquez M, Gadsby JR, Festa BP, Butler R, Jackson SP, Berno V, Luciani A, Devuyst O, Gallop JL. The phosphoinositide 3-kinase inhibitor alpelisib restores actin organization and improves proximal tubule dysfunction in vitro and in a mouse model of Lowe syndrome and Dent disease. Kidney Int. 2020 Oct;98(4):883-896. doi: 10.1016/j.kint.2020.05.040. Epub 2020 Sep 9. PMID: 32919786; PMCID: PMC7550850.

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Seo SW, Kim JM, Han DG, Geum D, Yun H, Yoon IS. A sensitive HPLC-FLD method for the quantification of alpelisib, a novel phosphatidylinositol 3-kinase inhibitor, in rat plasma: Drug metabolism and pharmacokinetic evaluation in vitro and in vivo. J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Jan 15;1163:122508. doi: 10.1016/j.jchromb.2020.122508. Epub 2020 Dec 19. PMID: 33387858.

1: Holzhauser S, Lukoseviciute M, Papachristofi C, Vasilopoulou C, Herold N, Wickström M, Kostopoulou ON, Dalianis T. Effects of PI3K and FGFR inhibitors alone and in combination, and with/without cytostatics in childhood neuroblastoma cell lines. Int J Oncol. 2021 Jan 5. doi: 10.3892/ijo.2021.5167. Epub ahead of print. PMID: 33491755.

2: Alizadeh SR, Hashemi SM. Development and therapeutic potential of 2-aminothiazole derivatives in anticancer drug discovery. Med Chem Res. 2021 Jan 15:1-36. doi: 10.1007/s00044-020-02686-2. Epub ahead of print. PMID: 33469255; PMCID: PMC7809097.

3: Zhao M, Scott S, Evans KW, Yuca E, Saridogan T, Zheng X, Wang H, Korkut A, Cruz Pico CX, Demirhan ME, Kirby B, Kopetz S, Diala I, Lalani AS, Piha-Paul S, Meric-Bernstam F. Combining neratinib with CDK4/6, mTOR and MEK inhibitors in models of HER2-positive cancer. Clin Cancer Res. 2021 Jan 7:clincanres.3017.2020. doi: 10.1158/1078-0432.CCR-20-3017. Epub ahead of print. PMID: 33414137.

4: Chteinberg E, Wetzels S, Gerritsen W, Temmerman L, van den Oord J, Biessen E, Kurz AK, Winnepenninckx V, Zenke M, Speel EJ, Zur Hausen A. Navitoclax combined with Alpelisib effectively inhibits Merkel cell carcinoma cell growth in vitro. Ther Adv Med Oncol. 2020 Dec 14;12:1758835920975621. doi: 10.1177/1758835920975621. PMID: 33403016; PMCID: PMC7739210.

5: Alpelisib Plus Letrozole Shows Promise After CDK 4/6 Inhibitor Therapy in PIK3CA-Mutated HR+/HER2- Advanced Breast Cancer. Oncologist. 2021 Jan 5. doi: 10.1002/onco.13662. Epub ahead of print. PMID: 33399247.

6: Lambertini M, Punie K. ESMO20 YO for YO: highlights on new drugs in advanced breast cancer focusing on sacituzumab govitecan and alpelisib. ESMO Open. 2020 Dec 15;6(1):100018. doi: 10.1016/j.esmoop.2020.100018. Epub ahead of print. PMID: 33399081.

7: Garneau AP, Haydock L, Tremblay LE, Isenring P. Somatic non-cancerous PIK3CA- related overgrowth syndrome treated with alpelisib in North America. J Mol Med (Berl). 2021 Jan 3. doi: 10.1007/s00109-020-02030-6. Epub ahead of print. PMID: 33392635.

8: Seo SW, Kim JM, Han DG, Geum D, Yun H, Yoon IS. A sensitive HPLC-FLD method for the quantification of alpelisib, a novel phosphatidylinositol 3-kinase inhibitor, in rat plasma: Drug metabolism and pharmacokinetic evaluation in vitro and in vivo. J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Jan 15;1163:122508. doi: 10.1016/j.jchromb.2020.122508. Epub 2020 Dec 19. PMID: 33387858.

9: Jia M, Liao N, Chen B, Zhang G, Wang Y, Li X, Cao L, Mok H, Ren C, Li K, Li C, Wen L, Lin J, Wei G, Balch CM. PIK3CA somatic alterations in invasive breast cancers: different spectrum from Caucasians to Chinese detected by next generation sequencing. Breast Cancer. 2021 Jan 1. doi: 10.1007/s12282-020-01199-5. Epub ahead of print. PMID: 33386585.

10: Wang S, Liu M, Lian S, Liu N, Zhang G, Zhao Q, Zhang Y, Jian L. Which Is the Most Appropriate PI3K Inhibitor for Breast Cancer Patients with or without PIK3CA Status Mutant? A Systematic Review and Network Meta-Analysis. Biomed Res Int. 2020 Dec 3;2020:7451576. doi: 10.1155/2020/7451576. PMID: 33376736; PMCID: PMC7739049.

11: Madhukar G, Subbarao N. In-silico prediction of potential inhibitors against phosphatidylinositol 3-kinase catalytic subunit alpha involved in head and neck squamous cell carcinomas. J Biomol Struct Dyn. 2020 Dec 24:1-16. doi: 10.1080/07391102.2020.1861980. Epub ahead of print. PMID: 33356909.

12: Eckerdt FD, Bell JB, Gonzalez C, Oh MS, Perez RE, Mazewski C, Fischietti M, Goldman S, Nakano I, Platanias LC. Combined PI3Kα-mTOR Targeting of Glioma Stem Cells. Sci Rep. 2020 Dec 14;10(1):21873. doi: 10.1038/s41598-020-78788-z. PMID: 33318517; PMCID: PMC7736588.

13: Matikas A, Foukakis T. SOLAR1s: alpelisib returns to earth? Ann Oncol. 2021 Feb;32(2):129-132. doi: 10.1016/j.annonc.2020.12.003. Epub 2020 Dec 9. PMID: 33309744.

14: André F, Ciruelos EM, Juric D, Loibl S, Campone M, Mayer IA, Rubovszky G, Yamashita T, Kaufman B, Lu YS, Inoue K, Pápai Z, Takahashi M, Ghaznawi F, Mills D, Kaper M, Miller M, Conte PF, Iwata H, Rugo HS. Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1. Ann Oncol. 2021 Feb;32(2):208-217. doi: 10.1016/j.annonc.2020.11.011. Epub 2020 Nov 25. PMID: 33246021.

15: Farah SJ, Masri N, Ghanem H, Azar M. DIABETIC KETOACIDOSIS ASSOCIATED WITH ALPELISIB TREATMENT OF METASTATIC BREAST CANCER. AACE Clin Case Rep. 2020 Sep 24;6(6):e349-e351. doi: 10.4158/ACCR-2020-0452. PMID: 33244501; PMCID: PMC7685409.

16: Armaghani AJ, Han HS. Alpelisib in the Treatment of Breast Cancer: A Short Review on the Emerging Clinical Data. Breast Cancer (Dove Med Press). 2020 Nov 18;12:251-258. doi: 10.2147/BCTT.S219436. PMID: 33239910; PMCID: PMC7680678.

17: Donahue S, Santos Fulgencio G. PI3K Inhibitors and Adverse Events: Optimizing Patient Care for the Treatment of Advanced Breast Cancer. Clin J Oncol Nurs. 2020 Dec 1;24(6):673-680. doi: 10.1188/20.CJON.673-680. PMID: 33216054.

18: Bertho M, Patsouris A, Augereau P, Robert M, Frenel JS, Blonz C, Campone M. A pharmacokinetic evaluation of alpelisib for the treatment of HR+, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer. Expert Opin Drug Metab Toxicol. 2020 Dec 8:1-14. doi: 10.1080/17425255.2021.1844662. Epub ahead of print. PMID: 33213227.

19: Huijberts SCFA, Boelens MC, Bernards R, Opdam FL. Mutational profiles associated with resistance in patients with BRAFV600E mutant colorectal cancer treated with cetuximab and encorafenib +/- binimetinib or alpelisib. Br J Cancer. 2021 Jan;124(1):176-182. doi: 10.1038/s41416-020-01147-2. Epub 2020 Nov 18. PMID: 33204026; PMCID: PMC7782586.

20: Nagaraj G, Ma CX. Clinical Challenges in the Management of Hormone Receptor- Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: A Literature Review. Adv Ther. 2020 Nov 15. doi: 10.1007/s12325-020-01552-2. Epub ahead of print. PMID: 33190190.



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