502632-66-8 Usage
Description
PX-866 is an analog of wortmannin, a potent phosphatidylinositol 3 kinase (PI3K) inhibitor. It selectively targets the p110α subunit of PI3K with high affinity (IC50=0.1 nM) and exhibits irreversible antitumor activity. PX-866 is also cell permeable, which allows it to effectively counteract hypoxia-related downregulation of E7 expression in HPV-positive cancer cells.
Uses
Used in Pharmaceutical Industry:
PX-866 is used as a PI3K inhibitor for its potent and selective inhibition of the p110α subunit, making it a valuable compound in the development of targeted cancer therapies.
Used in Cancer Research:
PX-866 is used as a research tool to study the role of PI3K in various cancer cell lines and to investigate the potential synergistic effects of combining PI3K inhibition with other therapeutic strategies.
Used in Drug Development:
PX-866 is used as a lead compound in the development of novel PI3K inhibitors, with the aim of improving the treatment of various types of cancer by targeting the PI3K signaling pathway.
Used in Anticancer Applications:
PX-866 is used as an anticancer agent due to its ability to inhibit PI3K, a key enzyme involved in cell survival and proliferation. Its irreversible inhibition of PI3K may lead to the suppression of tumor growth and progression in various cancer types.
Used in HPV-Positive Cancer Treatment:
PX-866 is used as a therapeutic agent for HPV-positive cancers, as it can counteract the hypoxia-related downregulation of E7 expression, which is a critical factor in the development and progression of these types of cancers.
in vitro
in previous study, px 866 was identified to be able to inhibit purified ptdins-3-kinase and ptdins-3-kinase signaling that was measured by phospho-ser473-akt levels in ht-29 colon cancer cells [1].
in vivo
animal study found that px-866 treatment at 10 mg/kg to mice could inhibit phospho-ser473-akt in ht-29 colon tumor xenografts up to 80% with recovery taking over 48 hours after oral administration but more rapidly after iv or ip route. in addition, px-866 had in-vivo antitumor activity against s.c. ovcar-3 human ovarian cancer and a-549 human lung cancer xenografts in immunodeficient mice. moreove, px-866 could also increase the antitumor activity of cisplatin against a-549 xenografts and radiation treatment against ovcar-3 xenografts [1].
Enzyme inhibitor
This orally active antifungal and antineoplastic agent (FW = 541.60 g/mol; CAS 502632-66-8; Solubility: 40 mg/mL DMSO, water-insoluble; stable for six months, when stored in a refrigerated desicator) is a chemically stable wortmannin derivative that potently and irreversibly inhibits phosphoinositide 3-kinase (IC50 = 0.1 nM) and phosphoinositide-3-kinasedependent signaling. PX-866 blocks PtdIns-3-kinase signaling, as measured by phospho-Ser473-Akt levels in HT-29 colon cancer cells (IC50 = 20 nM). PX-866 also overcomes resistance to the EGFR inhibitor gefitinib in A-549 human non-small cell lung cancer xenografts.
IC 50
0.1-88 nm
References
1) Ihle et al. (2004), Molecular pharmacology and antitumor activity of PK-866, a novel inhibitor of phosphoinositide-3-kinase signaling; Mol. Cancer Ther., 3 763
2) Bossler et al. (2019) Repression of Human Papilloma Virus Oncogene Expression Under Hypoxia is Mediated by PI3K/mTORC2/AKT Signaling; mBio,?10 e02323 [Focus Citation]
Check Digit Verification of cas no
The CAS Registry Mumber 502632-66-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 5,0,2,6,3 and 2 respectively; the second part has 2 digits, 6 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 502632-66:
(8*5)+(7*0)+(6*2)+(5*6)+(4*3)+(3*2)+(2*6)+(1*6)=118
118 % 10 = 8
So 502632-66-8 is a valid CAS Registry Number.
502632-66-8Relevant articles and documents
METHODS FOR TREATING ONCOVIRUS POSITIVE CANCERS
-
Page/Page column 82, (2012/09/21)
Provided herein are methods for the treatment of certain cancers in a subject by administering a PI-3 kinase inhibitor, or a combination of a PI-3 kinase inhibitor and a second anticancer agent, to the subject.
Wortmannin analogs and methods of using same in combination with chemotherapeutic agents
-
Page/Page column 1, (2008/06/13)
Novel wortmannin analogs and their use in inhibiting PI-3-kinase activity in mammals and the treatment or prevention of cancer and tumor formation in a subject are described herein. Preferably, the wortmannin analogs may be administered with other chemotherapeutic agents in the treatment of cancer.
