Brief Description

PI103 is a potent inhibitor with low IC50 values against recombinant PI3K isoforms p110alpha (IC50= 2 nM), p110beta (IC50= 3 nM), p110delta (IC50= 3 nM), and p110gamma (IC50= 15 nM), less potent to mTOR/DNA-PK with IC50 of 30 nM/23 nM.
IC50 value: 2 nM/3 nM/3 nM/15 nM (p110α/β/δ/γ)
Target: PI3K isoforms p110α/β/δ/γ
in vitro: the class I PI3K inhibitor, PI-103, enhances chemotherapy-induced cell death of GBM cells. Concurrent treatment with PI-103 and DNA-damaging drugs, in particular doxorubicin, significantly increases apoptosis and reduces colony formation compared with chemotherapy treatment alone. The underlying molecular mechanism for this chemosensitization was shown by two independent approaches, that is, pharmacological and genetic inhibition of PI3K, DNA-PK and mTOR, to involve inhibition of DNA-PK-mediated DNA repair. In human leukemic cell lines and in primary blast cells from AML patients, PI-103 inhibited constitutive and growth factor-induced PI3K/Akt and mTORC1 activation. PI-103 was essentially cytostatic for cell lines and induced cell cycle arrest in the G1 phase. In blast cells, PI-103 inhibited leukemic proliferation, the clonogenicity of leukemic progenitors and induced mitochondrial apoptosis, especially in the compartment containing leukemic stem cells.
in vivo: PI-103 significantly inhibited the growth of established, subcutaneous MYCN-amplified neuroblastoma xenografts in nude NMRI nu/nu mice. PI-103 inhibits proliferation and invasion, causes G(0)-G(1) arrest in cell cycle, and results in significant attenuation of orthotopic tumor growth in vivo.

Solubility

DMSO ≥22mg/mL Water <1.2mg/mL Ethanol <1.2mg/mL

Melting point

Boiling point

Density

Formula Weight:

Flash point

Storage conditions

Store at -20°C 2 years

Appearance:

White to off-white solid