Sonolisib | PX-866 | CAS#502632-66-8 | PI3K inhibitor

MedKoo Cat#: 202360 | Name: Sonolisib (PX-866)

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

Sonolisib (PX-866)

CAS#502632-66-8

Theoretical Analysis

MedKoo Cat#: 202360

Name: Sonolisib (PX-866)

CAS#: 502632-66-8

Chemical Formula: C29H35NO8

Exact Mass: 525.2363

Molecular Weight: 525.59

Elemental Analysis: C, 66.27; H, 6.71; N, 2.66; O, 24.35

Price and Availability

Size	Price	Availability	Quantity
10mg	USD 450.00
25mg	USD 750.00
50mg	USD 1,250.00
100mg	USD 1,750.00

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Related CAS #

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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

Appearance

Yellow 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 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).

HS Tariff Code

2934.99.9001

More Info

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.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#L7C05L30

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Sonolisib is an inhibitor of PI3K (IC50=0.1 nM (p110α), 1.0 nM (p120γ), 2.9 nM (p110δ)).

In vitro activity:

PX-866 could enhance EGFR inhibitors' efficacy in non-small cell lung cancer (NSCLC) and potentially other cancers resistant to EGFR inhibition. PX-866 enhanced gefitinib's effectiveness against NSCLC xenografts. PX-866 inhibited phospho-Akt in tumors but did not affect glucose tolerance. Prolonged PX-866 administration also caused increased neutrophil counts. Reference: Mol Cancer Ther. 2005 Sep;4(9):1349-57. https://pubmed.ncbi.nlm.nih.gov/16170026/

In vivo activity:

Combining PX-866 or PI-103 with the autophagy inhibitor 3-methyladenine (3-MA) affects apoptosis in T lymphoblastic leukemia cells. PX-866 and PI-103 treatment reduced cell viability while increasing apoptosis in CCRF-CEM and Jurkat cells, which was further enhanced when combined with 3-MA. The phosphorylation levels of AKT and mTOR were suppressed by PX-866 or PI-10. The expression of LC3, ATG5, ATG12 and Beclin-1 was upregulated by PX-866 or PI-103 and downregulated by 3-MA. Reference: Ann Clin Lab Sci. 2023 Jul;53(4):598-606. https://pubmed.ncbi.nlm.nih.gov/37625845/

	Solvent	mg/mL	mM
Solubility
	DMF	25.0	47.57
	DMSO	14.0	26.64
	Ethanol	25.0	47.57

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 525.59 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.

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. Dong YQ, Sun N, Yang XC, He MQ, Huang H, Guo WJ, Lin XJ. Suppression of Autophagy Can Augment PIK3 Inhibitor Induced Apoptosis in T Lymphoblastic Leukemia Cell Lines. Ann Clin Lab Sci. 2023 Jul;53(4):598-606. PMID: 37625845. 2. Aggarwal S, John S, Sapra L, Sharma SC, Das SN. Targeted disruption of PI3K/Akt/mTOR signaling pathway, via PI3K inhibitors, promotes growth inhibitory effects in oral cancer cells. Cancer Chemother Pharmacol. 2019 Mar;83(3):451-461. doi: 10.1007/s00280-018-3746-x. Epub 2018 Dec 5. PMID: 30519710. 3. Yam C, Xu X, Davies MA, Gimotty PA, Morrissette JJD, Tetzlaff MT, Wani KM, Liu S, Deng W, Buckley M, Zhao J, Amaravadi RK, Haas NB, Kudchadkar RR, Pavlick AC, Sosman JA, Tawbi H, Walker L, Schuchter LM, Karakousis GC, Gangadhar TC. A Multicenter Phase I Study Evaluating Dual PI3K and BRAF Inhibition with PX-866 and Vemurafenib in Patients with Advanced BRAF V600-Mutant Solid Tumors. Clin Cancer Res. 2018 Jan 1;24(1):22-32. doi: 10.1158/1078-0432.CCR-17-1807. Epub 2017 Oct 19. PMID: 29051322; PMCID: PMC5754240. 4. 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. doi: 10.1158/1535-7163.MCT-05-0149. PMID: 16170026; PMCID: PMC1432090.

In vitro protocol:

In vivo protocol:

1. Yam C, Xu X, Davies MA, Gimotty PA, Morrissette JJD, Tetzlaff MT, Wani KM, Liu S, Deng W, Buckley M, Zhao J, Amaravadi RK, Haas NB, Kudchadkar RR, Pavlick AC, Sosman JA, Tawbi H, Walker L, Schuchter LM, Karakousis GC, Gangadhar TC. A Multicenter Phase I Study Evaluating Dual PI3K and BRAF Inhibition with PX-866 and Vemurafenib in Patients with Advanced BRAF V600-Mutant Solid Tumors. Clin Cancer Res. 2018 Jan 1;24(1):22-32. doi: 10.1158/1078-0432.CCR-17-1807. Epub 2017 Oct 19. PMID: 29051322; PMCID: PMC5754240. 2. 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. doi: 10.1158/1535-7163.MCT-05-0149. PMID: 16170026; PMCID: PMC1432090.

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, BÃ¶gler 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.