Sonolisib (PX-866)
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MedKoo CAT#: 202360

CAS#: 502632-66-8

Description: Sonolisib, also known as PX-866, is a small-molecule wortmannin analogue inhibitor of the alpha, gamma, and delta isoforms of phosphoinositide 3-kinase (PI3K) with potential antineoplastic activity. PI3K inhibitor PX-866 inhibits the production of the secondary messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3) and activation of the PI3K/Akt signaling pathway, which may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.


Price and Availability

Size
Price

10mg
USD 450
100mg
USD 1750
Size
Price

25mg
USD 750
Size
Price

50mg
USD 1250

Sonolisib (PX-866), purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 202360
Name: Sonolisib (PX-866)
CAS#: 502632-66-8
Chemical Formula: C29H35NO8
Exact Mass: 525.23627
Molecular Weight: 525.59
Elemental Analysis: C, 66.27; H, 6.71; N, 2.66; O, 24.35


Synonym: PX866; PX866; PX 866; Sonolisib

IUPAC/Chemical Name: (4S,4aR,5R,6aS,9aR,E)-1-((diallylamino)methylene)-11-hydroxy-4-(methoxymethyl)-4a,6a-dimethyl-2,7,10-trioxo-1,2,4,4a,5,6,6a,7,8,9,9a,10-dodecahydroindeno[4,5-h]isochromen-5-yl acetate

InChi Key: QIUASFSNWYMDFS-NILGECQDSA-N

InChi Code: InChI=1S/C29H35NO8/c1-7-11-30(12-8-2)14-17-23-26(34)25(33)22-18-9-10-20(32)28(18,4)13-19(37-16(3)31)24(22)29(23,5)21(15-36-6)38-27(17)35/h7-8,14,18-19,21,34H,1-2,9-13,15H2,3-6H3/b17-14+/t18-,19+,21+,28-,29-/m0/s1

SMILES Code: CC(O[C@@H](C1=C2C(C(O)=C3/C(C(O[C@H](COC)[C@]13C)=O)=C\N(CC=C)CC=C)=O)C[C@]4(C)C(CC[C@]42[H])=O)=O


Technical Data

Appearance:
Yellow solid powder

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

Certificate of Analysis:

Safety Data Sheet (MSDS):

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 at 200 mg/mL; soluble in ethanol at 200 mg/mL; very poorly soluble 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).

Harmonized System Code:
293490


Additional Information

  
PX-866 is an orally available nanomolar pan-inhibitor of PI-3K whose administration results in antitumor activity and pathway (AKT, S6 and mTOR) inhibition in animal models. Loss of PTEN and/or PI 3K mutations have been associated with enhanced susceptibility to PX-866. PX-866 is being evaluated in a phase 1 clinical trial to determine the MTD, and measure safety, pharmacokinetic (PK) and pharmacodynamic (PD) endpoints in PBMCs and tumor tissue in patients with solid tumors. Conclusions: PX-866 is a novel oral PI-3K inhibitor that is undergoing development in a clinical trial with built-in PD endpoints. PX-866 has shown to have a mild side effect profile while inducing stabilization of disease in previously progressing cancer patients. Oral PX-866 provides target inhibition even at low drug doses and inhibition is maintained for an extended time following the last dose. See asco.com. website.
  


References

1: Bowles DW, Ma WW, Senzer N, Brahmer JR, Adjei AA, Davies M, Lazar AJ, Vo A, Peterson S, Walker L, Hausman D, Rudin CM, Jimeno A. A multicenter phase 1 study of PX-866 in combination with docetaxel in patients with advanced solid tumours. Br J Cancer. 2013 Sep 3;109(5):1085-92. doi: 10.1038/bjc.2013.474. Epub 2013 Aug 13. PubMed PMID: 23942080; PubMed Central PMCID: PMC3778312.

2: Hong DS, Bowles DW, Falchook GS, Messersmith WA, George GC, O'Bryant CL, Vo AC, Klucher K, Herbst RS, Eckhardt SG, Peterson S, Hausman DF, Kurzrock R, Jimeno A. A multicenter phase I trial of PX-866, an oral irreversible phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors. Clin Cancer Res. 2012 Aug 1;18(15):4173-82. doi: 10.1158/1078-0432.CCR-12-0714. Epub 2012 Jun 12. PubMed PMID: 22693357.

3: Gwak HS, Shingu T, Chumbalkar V, Hwang YH, DeJournett R, Latha K, Koul D, Alfred Yung WK, Powis G, Farrell NP, Bögler O. Combined action of the dinuclear platinum compound BBR3610 with the PI3-K inhibitor PX-866 in glioblastoma. Int J Cancer. 2011 Feb 15;128(4):787-96. doi: 10.1002/ijc.25394. PubMed PMID: 20473884; PubMed Central PMCID: PMC2990813.

4: Koul D, Shen R, Kim YW, Kondo Y, Lu Y, Bankson J, Ronen SM, Kirkpatrick DL, Powis G, Yung WK. Cellular and in vivo activity of a novel PI3K inhibitor, PX-866, against human glioblastoma. Neuro Oncol. 2010 Jun;12(6):559-69. doi: 10.1093/neuonc/nop058. Epub 2010 Feb 15. PubMed PMID: 20156803; PubMed Central PMCID: PMC2940638.

5: Le Cras TD, Korfhagen TR, Davidson C, Schmidt S, Fenchel M, Ikegami M, Whitsett JA, Hardie WD. Inhibition of PI3K by PX-866 prevents transforming growth factor-alpha-induced pulmonary fibrosis. Am J Pathol. 2010 Feb;176(2):679-86. doi: 10.2353/ajpath.2010.090123. Epub 2009 Dec 30. PubMed PMID: 20042669; PubMed Central PMCID: PMC2808075.

6: Ihle NT, Lemos R, Schwartz D, Oh J, Halter RJ, Wipf P, Kirkpatrick L, Powis G. Peroxisome proliferator-activated receptor gamma agonist pioglitazone prevents the hyperglycemia caused by phosphatidylinositol 3-kinase pathway inhibition by PX-866 without affecting antitumor activity. Mol Cancer Ther. 2009 Jan;8(1):94-100. doi: 10.1158/1535-7163.MCT-08-0714. PubMed PMID: 19139117; PubMed Central PMCID: PMC2633941.

7: Ihle NT, Lemos R Jr, Wipf P, Yacoub A, Mitchell C, Siwak D, Mills GB, Dent P, Kirkpatrick DL, Powis G. Mutations in the phosphatidylinositol-3-kinase pathway predict for antitumor activity of the inhibitor PX-866 whereas oncogenic Ras is a dominant predictor for resistance. Cancer Res. 2009 Jan 1;69(1):143-50. doi: 10.1158/0008-5472.CAN-07-6656. PubMed PMID: 19117997; PubMed Central PMCID: PMC2613546.

8: Howes AL, Chiang GG, Lang ES, Ho CB, Powis G, Vuori K, Abraham RT. The phosphatidylinositol 3-kinase inhibitor, PX-866, is a potent inhibitor of cancer cell motility and growth in three-dimensional cultures. Mol Cancer Ther. 2007 Sep;6(9):2505-14. Epub 2007 Aug 31. PubMed PMID: 17766839.

9: Ihle NT, Paine-Murrieta G, Berggren MI, Baker A, Tate WR, Wipf P, Abraham RT, Kirkpatrick DL, Powis G. The phosphatidylinositol-3-kinase inhibitor PX-866 overcomes resistance to the epidermal growth factor receptor inhibitor gefitinib in A-549 human non-small cell lung cancer xenografts. Mol Cancer Ther. 2005 Sep;4(9):1349-57. PubMed PMID: 16170026; PubMed Central PMCID: PMC1432090.

10: Ihle NT, Williams R, Chow S, Chew W, Berggren MI, Paine-Murrieta G, Minion DJ, Halter RJ, Wipf P, Abraham R, Kirkpatrick L, Powis G. Molecular pharmacology and antitumor activity of PX-866, a novel inhibitor of phosphoinositide-3-kinase signaling. Mol Cancer Ther. 2004 Jul;3(7):763-72. PubMed PMID: 15252137.