PKI-402

SKU: orb1226884

Description

A potent dual PI3K/mTOR inhibitor with IC50 of 1/7/16/14/1.7 nM for PI3Kα/β/γ/δ/mTOR respectively; shows excellent suppression of Akt T308 phosphorylation (IC50=5 nM), and excellent inhibition of cell proliferation in several human cancer cell lines; shows excellent in vivo efficacy in various human cancer xenografts, good physical properties and PK parameters.

Key Properties

• CAS Number: 1173204-81-3
• MW: 570.6454
• Purity: >98% (HPLC)
• Formula: C₂₉H₃₄N₁₀O₃
• SMILES: O=C(NC1=CC=C(C(N2CCN(C)CC2)=O)C=C1)NC3=CC=C(C4=NC(N5CCOCC5)=C(N=NN6CC)C6=N4)C=C3
• Target: PI3K
• Solubility: DMSO: < 1 mg/mL

Bioactivity

• In Vivo:
  PKI-402 displays antitumor activity (i. v. route) in breast [MDA-MB-361: Her2+ and PIK3CA (E545K)], glioma (U87MG and PTEN), and NSCLC (A549; K-Ras and STK11) xenograft models. PKI-402 causes regression in the MDA-MB-361 xenograft model. PKI-402 effect is most pronounced at 100 mg/kg (daily for 5 days, one round), which reduces initial tumor volume and prevents tumor re-growth for 70 days. In MDA-MB-361 tumor tissue, PKI-402 at 100 mg/kg (single dose) fully suppresses p-Akt at both the T308 and the S473 sites at 8 hours and induces cleaved PARP. At 24 hours, p-Akt suppression is still evident, as is cleaved PARP.
• In Vitro:
  PKI-402 is an equipotent inhibitor of class I PI3K, including the E545K and H1047R PI3K-α mutants (IC50 = 2, 3 and 3 nM for PI3Kα, PI3Kα-H1047R and PI3Kα-E545K, respectively). PKI-402 causes in vitro growth inhibition of human tumor cell lines derived from a diverse set of human tumor tissues, including breast, brain (glioma), pancreas, and non-small cell lung cancer (NSCLC) tissues. PKI-402 inhibits MDA-MB-361 [breast: Her2+ and PIK3CA mutant (E545K)], with an IC50 of 6 nM. PKI-402 inhibits HCT116 (K-Ras and PIK3CA mutant) with an IC50 of 33 nM.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

PKI 402 | PKI402

Quick Database Links

Gene Symbol

PI3K