Sapanisertib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Sapanisertib (INK-128, MLN0128) 是一种有效的 ATP 竞争性、口服活性双 mTORC1/2 抑制剂，在无细胞测定中 Ki 为 1.4 nM。

Sapanisertib (INK-128, MLN0128) is a potent, ATP-competitive, orally active dual mTORC1/2 inhibitor with Ki of 1.4 nM in cell-free assays, >200-fold selectivity over calss I PI3K isoforms; inhibits both the phosphorylation of S6 and 4EBP1, the downstream substrates of TORC1, and selectively inhibits AKT phosphorylation at Ser473, the downstream substrate of TORC2; also shows potent inhibition effects on cell lines resistant to rapamycin and pan-PI3K inhibitors; shows tumor growth inhibition efficacy in multiplexenograft models.Brain Cancer Phase 2 Clinical(In Vitro):Sapanisertib (INK-128) exhibits an enzymatic inhibition activity against mTOR and more than 100-fold selectivity to PI3K kinases. Sapanisertib (INK-128) selectively decreases the expression of YB1, MTA1, vimentin and CD44 at the protein but not transcript level in PC3 cells. Sapanisertib (INK-128) decreases the invasive potential of PC3 prostate cancer cells. Furthermore, Sapanisertib (INK-128) inhibits cancer cell migration starting at 6 h of treatment, precisely correlating with when decreases in the expression of pro-invasion genes are evident, but preceding any changes in the cell cycle or overall global protein synthesis.(In Vivo):In a ZR-75-1 breast cancer xenograft model, Sapanisertib (INK-128) shows tumor growth inhibition efficacy at a dose of 0.3 mg/kg/day. 4EBP1 and p70S6K1/2 phosphorylation is completely restored to wild-type levels after treatment with INK128 in PtenL/L mice. Sapanisertib (INK-128) treatment results in a 50% decrease in prostatic intraepithelial neoplasia (PIN) lesions in PtenL/L mice and induces programmed cell death in multiple cancer cell lines in mice.

Sapanisertib (INK-128) exhibits an enzymatic inhibition activity against mTOR and more than 100-fold selectivity to PI3K kinases. Sapanisertib (INK-128) selectively decreases the expression of YB1, MTA1, vimentin and CD44 at the protein but not transcript level in PC3 cells. Sapanisertib (INK-128) decreases the invasive potential of PC3 prostate cancer cells. Furthermore, Sapanisertib (INK-128) inhibits cancer cell migration starting at 6 h of treatment, precisely correlating with when decreases in the expression of pro-invasion genes are evident, but preceding any changes in the cell cycle or overall global protein synthesis.

In a ZR-75-1 breast cancer xenograft model, Sapanisertib (INK-128) shows tumor growth inhibition efficacy at a dose of 0.3 mg/kg/day. 4EBP1 and p70S6K1/2 phosphorylation is completely restored to wild-type levels after treatment with INK128 in PtenL/L mice. Sapanisertib (INK-128) treatment results in a 50% decrease in prostatic intraepithelial neoplasia (PIN) lesions in PtenL/L mice and induces programmed cell death in multiple cancer cell lines in mice.

INK-128 | MLN0128

PI3K/Akt/mTOR signaling

mTOR

mTOR|PI3Kα|PI3Kγ|PI3Kδ

Cancer

Brain Cancer

1224844-38-5

309.33

C15H15N7O

>98% (HPLC)

10 mM in DMSO

NC1=C2C(N(C(C)C)N=C2C3=CC=C(OC(N)=N4)C4=C3)=NC=N1

1H-Pyrazolo[3,4-d]pyrimidin-4-amine, 3-(2-amino-5-benzoxazolyl)-1-(1-methylethyl)-

(-20℃)

With Ice Pack

≥ 2 years