PKI-402 is a selective, reversible, ATP-competitive, equipotent class I phosphatidylinositol 3-kinases (PI3K) inhibitor with IC50 of 1, 7, 16 and 14 nM for PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ, respectively. PKI-402 gave rise to in vitro growth inhibition of human tumor cell lines derived from breast, brain (glioma), pancreas, and non small cell lung cancer (NSCLC) tissues. In many cases IC50 values were <100 nm. in vitro, pki-402 suppressed phosphorylation of pi3k and mtor effect or proteins, particularly p-akt at threonine308 (t308), concentrations that closely matched those inhibited tumor cell growth. mda361, a breast line with elevated levels her2 receptor, mutant pi3k- (e545k), 30 nm triggered cleaved parp, marker for apoptosis. vivo, revealed anti-tumor activity when administered by iv route glioma (u87mg, pten), nsclc (a549; k-ras, stk11), (mda361: her2+, pik3ca [e545k]) xenograft models. 25, 50, 100 mg>

>98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

PKI402

DMSO ：0.4 mg/mL (0.7 mM)

PI3Kα ,mTOR ,PI3Kβ ,PI3Kδ ,PI3Kγ

Equivalent to the IC50 for wild-type PI3Kα, PKI-402 inhibits E545K and H1047R PI3Kα mutants with IC50 of 3 nM. In a panel of 236 human protein kinases, PKI-402 only displays inhibitory activity against C-Raf and B-Raf with IC50 of 7 μM, and displays little activity against all other kinases with IC50 of > 10 μM. PKI-402 inhibits the growth of human tumor cell lines with IC50 of 6-349 nM. Consistently, PKI-402 inhibits phosphorylation of PI3K and mTOR effector proteins, particularly phosphorylated Akt (p-Akt) at T308 and S473 with IC50 of

Single dose of PKI-402 (100 mg/kg) suppresses Akt phosphorylation (at T308) and induces cleaved PARP in MDA-MB-361 tumors. In normal tissue (heart and lung), PKI-402 (100 mg/kg) has minimal effect on p-Akt, with no detectable cleaved PARP. Consistently, PKI-402 at 100 mg/kg (daily for 5 days, one round) reduces initial tumor volume of 260 mm3 to 129 mm3 and prevents tumor regrowth for 70 days in MDA-MB-361. PKI-402 significantly inhibits the growth of A549 tumors in nude mice at 25 mg/kg and 50 mg/kg. PKI-402 at 100 mg/kg (daily for 5 days, one round) causes significant (P