PX-866 Property

Boiling point:

651.4±55.0 °C(Predicted)

Density 

1.28

storage temp. 

2-8°C

solubility 

Soluble in DMSO (up to 25 mg/ml).

form 

solid

pka

8.35±0.70(Predicted)

color 

Orange

Stability:

Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 2 months.

CAS DataBase Reference

502632-66-8

Safety

HS Code 

29329990

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

Precautionary statements

P260Do not breathe dust/fume/gas/mist/vapours/spray.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P312Call a POISON CENTER or doctor/physician if you feel unwell.

PX-866 Chemical Properties,Usage,Production

Description

PX-866 (502632-66-8) inhibits PI-3 Kinase with selectivity for p110α (IC50=0.1 nM). Counteracts hypoxia-related downregulation of E7 expression in HPV-positive cancer cells.2 Displays antitumor activity. Irreversible. Cell permeable.

Uses

PX-866 is an analog of wortmannin (W499400). Wortmannin is a phosphatidylinositol 3 kinase (PI3K) inhibitor. Potent PI3K inhibitor.

Definition

ChEBI: PX-866 is an organic heterotetracyclic compound that is obtained from wortmanin via aminolysis of its furan ring by diallyl amine. It has a role as an EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor. It is an organic heterotetracyclic compound, a delta-lactone, an acetate ester and a tertiary amino compound. It is functionally related to a wortmannin.

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]