PI-103 Hydrochloride is a dual PI3K and mTOR inhibitor with IC50s of 8 nM, 88 nM, 48 nM, 150 nM, 20 nM, and 83 nM for p110α, p110β, p110δ, p110γ, mTORC1, and mTORC2. PI-103 Hydrochloride also inhibits DNA-PK with an IC50 of 2 nM. PI-103 Hydrochloride induces autophagy.
体外研究
PI-103 exhibits antiproliferative properties in a panel of human cancer cell lines. PI-103 is essentially cytostatic for cell lines and induced cell cycle arrest in the G1 phase. In blast cells, PI-103 inhibits leukemic proliferation, the clonogenicity of leukemic progenitors and induces mitochondrial apoptosis, especially in the compartment containing leukemic stem cells . PI-103 potently inhibits both the rapamycin-sensitive (mTORC1, IC50=20 nM) and rapamycin-insensitive (mTORC2, IC50=83 nM) complexes of the protein kinase mTOR.
体内研究
PI-103 shows therapeutic activity against a range of human tumor xenografts, exhibiting inhibition of angiogenesis, invasion, and metastasis, as well as direct antiproliferative effects. PI-103 induces immunosuppression promoting in vivo tumor growth and inhibiting apoptosis. Tumors from PI-103-treated mice shows higher levels of cyclin D1 and more proliferating cells.
分子式
C19H17ClN4O3
分子量
384.82
CAS号
371935-79-4
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : 4.1 mg/mL (10.65 mM; Need ultrasonic and warming)
H2O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)