Voxtalisib
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MedKoo CAT#: 203187

CAS#: 934493-76-2

Description: Voxtalisib, also known as XL-765 and SAR245409, is a PI3K/mTOR dual kinase inhibitor XL765 is an orally bioavailable small molecule targeting the phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR) kinases in the PI3K/mTOR signaling pathway, with potential antineoplastic activity. PI3K/mTOR dual kinase inhibitor XL765 inhibits both PI3K kinase and mTOR kinase, which may result in tumor cell apoptosis and growth inhibition in susceptible tumor cell populations.

Chemical Structure

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Voxtalisib
CAS# 934493-76-2
Instruction

Theoretical Analysis

MedKoo Cat#: 203187
Name: Voxtalisib
CAS#: 934493-76-2
Chemical Formula: C13H14N6O
Exact Mass: 270.12
Molecular Weight: 270.296
Elemental Analysis: C, 57.77; H, 5.22; N, 31.09; O, 5.92

Price and Availability

Size Price Availability Quantity
5mg USD 350 2 Weeks
10mg USD 550 2 Weeks
25mg USD 1250 2 Weeks
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Related CAS #: 1349796-36-6   934493-76-2   Voxtalisib HCl  

Synonym: XL765; XL 765; XL-765; SAR245409; SAR245409; SAR 245409; Voxtalisib.

IUPAC/Chemical Name: 2-Amino-8-ethyl-4-methyl-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one

InChi Key: RGHYDLZMTYDBDT-UHFFFAOYSA-N

InChi Code: InChI=1S/C13H14N6O/c1-3-19-11-8(7(2)16-13(14)17-11)6-9(12(19)20)10-4-5-15-18-10/h4-6H,3H2,1-2H3,(H,15,18)(H2,14,16,17)

SMILES Code: O=C1C(C2=CC=NN2)=CC3=C(C)N=C(N)N=C3N1CC

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.

Shelf Life: >2 years if stored properly

Drug Formulation: This drug is 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

More Info:

Biological target:
In vitro activity:
In vivo activity:

Preparing Stock Solutions

The following data is based on the product molecular weight 270.30 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:
In vitro protocol:
In vivo protocol:

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1: Thijssen R, Ter Burg J, van Bochove GG, de Rooij MF, Kuil A, Jansen MH, Kuijpers TW, Baars JW, Virone-Oddos A, Spaargaren M, Egile C, van Oers MH, Eldering E, Kersten MJ, Kater AP. The pan phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor SAR245409 (voxtalisib/XL765) blocks survival, adhesion and proliferation of primary chronic lymphocytic leukemia cells. Leukemia. 2016 Sep;30(9):1963. doi: 10.1038/leu.2016.184. PubMed PMID: 27600169.

2: Vogel KR, Ainslie GR, Gibson KM. mTOR inhibitors rescue premature lethality and attenuate dysregulation of GABAergic/glutamatergic transcription in murine succinate semialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism. J Inherit Metab Dis. 2016 Nov;39(6):877-886. Epub 2016 Aug 12. PubMed PMID: 27518770; PubMed Central PMCID: PMC5114712.

3: Awan FT, Gore L, Gao L, Sharma J, Lager J, Costa LJ. Phase Ib trial of the PI3K/mTOR inhibitor voxtalisib (SAR245409) in combination with chemoimmunotherapy in patients with relapsed or refractory B-cell malignancies. Br J Haematol. 2016 Oct;175(1):55-65. doi: 10.1111/bjh.14181. Epub 2016 Jun 13. PubMed PMID: 27293194.

4: Inaba K, Oda K, Aoki K, Sone K, Ikeda Y, Miyasaka A, Kashiyama T, Fukuda T, Makii C, Arimoto T, Wada-Hiraike O, Kawana K, Yano T, Osuga Y, Fujii T. Synergistic antitumor effects of combination PI3K/mTOR and MEK inhibition (SAR245409 and pimasertib) in mucinous ovarian carcinoma cells by fluorescence resonance energy transfer imaging. Oncotarget. 2016 May 17;7(20):29577-91. doi: 10.18632/oncotarget.8807. PubMed PMID: 27102436; PubMed Central PMCID: PMC5045418.

5: Radoul M, Chaumeil MM, Eriksson P, Wang AS, Phillips JJ, Ronen SM. MR Studies of Glioblastoma Models Treated with Dual PI3K/mTOR Inhibitor and Temozolomide:Metabolic Changes Are Associated with Enhanced Survival. Mol Cancer Ther. 2016 May;15(5):1113-22. doi: 10.1158/1535-7163.MCT-15-0769. Epub 2016 Feb 16. PubMed PMID: 26883274; PubMed Central PMCID: PMC4873419.

6: Lee J, Galloway R, Grandjean G, Jacob J, Humphries J, Bartholomeusz C, Goodstal S, Lim B, Bartholomeusz G, Ueno NT, Rao A. Comprehensive Two- and Three-Dimensional RNAi Screening Identifies PI3K Inhibition as a Complement to MEK Inhibitor AS703026 for Combination Treatment of Triple-Negative Breast Cancer. J Cancer. 2015 Oct 28;6(12):1306-19. doi: 10.7150/jca.13266. eCollection 2015. PubMed PMID: 26640591; PubMed Central PMCID: PMC4643087.

7: Blackwell K, Burris H, Gomez P, Lynn Henry N, Isakoff S, Campana F, Gao L, Jiang J, Macé S, Tolaney SM. Phase I/II dose-escalation study of PI3K inhibitors pilaralisib or voxtalisib in combination with letrozole in patients with hormone-receptor-positive and HER2-negative metastatic breast cancer refractory to a non-steroidal aromatase inhibitor. Breast Cancer Res Treat. 2015 Nov;154(2):287-97. doi: 10.1007/s10549-015-3615-9. Epub 2015 Oct 24. PubMed PMID: 26497877.

8: Thijssen R, Ter Burg J, van Bochove GG, de Rooij MF, Kuil A, Jansen MH, Kuijpers TW, Baars JW, Virone-Oddos A, Spaargaren M, Egile C, van Oers MH, Eldering E, Kersten MJ, Kater AP. The pan phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor SAR245409 (voxtalisib/XL765) blocks survival, adhesion and proliferation of primary chronic lymphocytic leukemia cells. Leukemia. 2016 Feb;30(2):337-45. doi: 10.1038/leu.2015.241. Epub 2015 Sep 4. PubMed PMID: 26338274.

9: Gravina GL, Mancini A, Scarsella L, Colapietro A, Jitariuc A, Vitale F, Marampon F, Ricevuto E, Festuccia C. Dual PI3K/mTOR inhibitor, XL765 (SAR245409), shows superior effects to sole PI3K [XL147 (SAR245408)] or mTOR [rapamycin] inhibition in prostate cancer cell models. Tumour Biol. 2016 Jan;37(1):341-51. doi: 10.1007/s13277-015-3725-3. Epub 2015 Jul 29. PubMed PMID: 26219891.

10: Durbas M, Horwacik I, Boratyn E, Kamycka E, Rokita H. GD2 ganglioside specific antibody treatment downregulates PI3K/Akt/mTOR signaling network in human neuroblastoma cell lines. Int J Oncol. 2015 Sep;47(3):1143-59. doi: 10.3892/ijo.2015.3070. Epub 2015 Jul 2. PubMed PMID: 26134970.

11: Inaba K, Oda K, Ikeda Y, Sone K, Miyasaka A, Kashiyama T, Fukuda T, Uehara Y, Arimoto T, Kuramoto H, Wada-Hiraike O, Kawana K, Yano T, Osuga Y, Fujii T. Antitumor activity of a combination of dual PI3K/mTOR inhibitor SAR245409 and selective MEK1/2 inhibitor pimasertib in endometrial carcinomas. Gynecol Oncol. 2015 Aug;138(2):323-31. doi: 10.1016/j.ygyno.2015.05.031. Epub 2015 May 29. PubMed PMID: 26033306.

12: Wen PY, Omuro A, Ahluwalia MS, Fathallah-Shaykh HM, Mohile N, Lager JJ, Laird AD, Tang J, Jiang J, Egile C, Cloughesy TF. Phase I dose-escalation study of the PI3K/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma. Neuro Oncol. 2015 Sep;17(9):1275-83. doi: 10.1093/neuonc/nov083. Epub 2015 May 26. PubMed PMID: 26019185; PubMed Central PMCID: PMC4588757.

13: Papadopoulos KP, Egile C, Ruiz-Soto R, Jiang J, Shi W, Bentzien F, Rasco D, Abrisqueta P, Vose JM, Tabernero J. Efficacy, safety, pharmacokinetics and pharmacodynamics of SAR245409 (voxtalisib, XL765), an orally administered phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor: a phase 1 expansion cohort in patients with relapsed or refractory lymphoma. Leuk Lymphoma. 2015 Jun;56(6):1763-70. doi: 10.3109/10428194.2014.974040. Epub 2014 Nov 19. PubMed PMID: 25300944.

14: Yu P, Laird AD, Du X, Wu J, Won KA, Yamaguchi K, Hsu PP, Qian F, Jaeger CT, Zhang W, Buhr CA, Shen P, Abulafia W, Chen J, Young J, Plonowski A, Yakes FM, Chu F, Lee M, Bentzien F, Lam ST, Dale S, Matthews DJ, Lamb P, Foster P. Characterization of the activity of the PI3K/mTOR inhibitor XL765 (SAR245409) in tumor models with diverse genetic alterations affecting the PI3K pathway. Mol Cancer Ther. 2014 May;13(5):1078-91. doi: 10.1158/1535-7163.MCT-13-0709. Epub 2014 Mar 14. PubMed PMID: 24634413.

15: Papadopoulos KP, Tabernero J, Markman B, Patnaik A, Tolcher AW, Baselga J, Shi W, Egile C, Ruiz-Soto R, Laird AD, Miles D, Lorusso PM. Phase I safety, pharmacokinetic, and pharmacodynamic study of SAR245409 (XL765), a novel, orally administered PI3K/mTOR inhibitor in patients with advanced solid tumors. Clin Cancer Res. 2014 May 1;20(9):2445-56. doi: 10.1158/1078-0432.CCR-13-2403. Epub 2014 Feb 28. PubMed PMID: 24583798.

16: Jänne PA, Cohen RB, Laird AD, Macé S, Engelman JA, Ruiz-Soto R, Rockich K, Xu J, Shapiro GI, Martinez P, Felip E. Phase I safety and pharmacokinetic study of the PI3K/mTOR inhibitor SAR245409 (XL765) in combination with erlotinib in patients with advanced solid tumors. J Thorac Oncol. 2014 Mar;9(3):316-23. doi: 10.1097/JTO.0000000000000088. PubMed PMID: 24496004.

17: Dai C, Zhang B, Liu X, Ma S, Yang Y, Yao Y, Feng M, Bao X, Li G, Wang J, Guo K, Ma W, Xing B, Lian W, Xiao J, Cai F, Zhang H, Wang R. Inhibition of PI3K/AKT/mTOR pathway enhances temozolomide-induced cytotoxicity in pituitary adenoma cell lines in vitro and xenografted pituitary adenoma in female nude mice. Endocrinology. 2013 Mar;154(3):1247-59. doi: 10.1210/en.2012-1908. Epub 2013 Feb 5. PubMed PMID: 23384836.

18: Ghadimi MP, Lopez G, Torres KE, Belousov R, Young ED, Liu J, Brewer KJ, Hoffman A, Lusby K, Lazar AJ, Pollock RE, Lev D. Targeting the PI3K/mTOR axis, alone and in combination with autophagy blockade, for the treatment of malignant peripheral nerve sheath tumors. Mol Cancer Ther. 2012 Aug;11(8):1758-69. doi: 10.1158/1535-7163.MCT-12-0015. Epub 2012 Jul 30. PubMed PMID: 22848094; PubMed Central PMCID: PMC3416967.

19: Mirzoeva OK, Hann B, Hom YK, Debnath J, Aftab D, Shokat K, Korn WM. Autophagy suppression promotes apoptotic cell death in response to inhibition of the PI3K-mTOR pathway in pancreatic adenocarcinoma. J Mol Med (Berl). 2011 Sep;89(9):877-89. doi: 10.1007/s00109-011-0774-y. Epub 2011 Jun 16. PubMed PMID: 21678117.

20: Prasad G, Sottero T, Yang X, Mueller S, James CD, Weiss WA, Polley MY, Ozawa T, Berger MS, Aftab DT, Prados MD, Haas-Kogan DA. Inhibition of PI3K/mTOR pathways in glioblastoma and implications for combination therapy with temozolomide. Neuro Oncol. 2011 Apr;13(4):384-92. doi: 10.1093/neuonc/noq193. Epub 2011 Feb 11. PubMed PMID: 21317208; PubMed Central PMCID: PMC3064692.