PI 3-K Inhibitor XI, HWT

Toxicity: Standard Handling (A)

Zask, A., et al. 2008. J. Med. Chem.51, 1319.
Zhu, T., et al. 2006. J. Med. Chem.49, 1373.
Norman, B. H., et al. 1996. J. Med. Chem.39, 1106.
Gelas, P., et al. 1992. Biochem. J.287, 67.

Packaged under inert gas

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

A cell-permeable Wortmannin (Cat. Nos. 681675 and 681676) 17β-Hydroxy analog (HWT) that acts as an irreversible PI 3-K inhibitor with an 8.4-fold higher potency than that of Wortmannin (IC₅₀ = 0.5 and 4.2 nM, respectively) and inhibits mTOR only at much higher concentrations (IC₅₀ = 0.193 µM). Both Wortmannin and HWT covalently modify a conserved lysine residue (Lys833 in porcine PI 3-Kγ) in the PI 3-K ATP binding pocket via their electrophilic furan ring at C-20 position. HWT is shown to effectively arrest the growth of LNCaP cells (IC₅₀ = 1.464 µM) in vitro, however, its high in vivo toxicity renders it unsuitable for tumor killing studies in mice. Also reported to inhibit late phase PLD-mediated PA production upon fMLP (Cat. No. 05-22-2500) stimulation of human neutrophils.