Molecular Weight (MW)

309.33

Formula

C15H15N7O

CAS No.

1224844-38-5

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 62 mg/mL (200.4 mM)

Water: <1 mg/mL

Ethanol: 2 mg/mL (6.5 mM)

Solubility (In vivo)

30% PEG400+0.5% Tween80+5% propylene glycol: 30mg/mL

Synonyms

MLN-0128; Sapanisertib; TAK-228; TAK 228; TAK228; INK128; INK-128; INK 128; MLN0128; MLN 0128; MLN-0128

Chemical Name: 3-(2-amino-5-benzoxazolyl)-1-(1-methylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

InChi Key: GYLDXIAOMVERTK-UHFFFAOYSA-N

InChi Code: InChI=1S/C15H15N7O/c1-7(2)22-14-11(13(16)18-6-19-14)12(21-22)8-3-4-10-9(5-8)20-15(17)23-10/h3-7H,1-2H3,(H2,17,20)(H2,16,18,19)

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

In Vitro

Kinase Assay: Sapanisertib (INK-128) is a ATP-dependent mTOR1/2 inhibitor with an IC50 of 1 nM for mTOR kinase. Sapanisertib (INK-128) exhibits an enzymatic inhibition activity against mTOR and more than 100-fold selectivity to PI3K kinases.

Cell Assay: INK 128 exhibits an enzymatic inhibition activity against mTOR and more than 100-fold selectivity to PI3K kinases. As TORC1/2 inhibitor, INK 128 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. Furthermore, INK 128 also shows potent inhibition effects on cell lines resistant to rapamycin and pan-PI3K inhibitors.

In Vivo

In a ZR-75-1 breast cancer xenograft model, INK 128 shows tumor growth inhibition efficacy at a dose of 0.3 mg/kg/day. Daily, oral administration of INK 128 inhibits angiogenesis and tumor growth in multiplexenograft models.

Animal model

Nude Mice

Formulation & Dosage

Nude mice are inoculated subcutaneously in the right subscapular region with 5×106 MDA-MB-361 cells. After tumours reach a size of 150-200 mm3, mice are randomLy assigned into vehicle control or treatment groups. Sapanisertib (INK-128) is formulated in 5% polyvinylpropyline, 15% NMP, 80% water and administered by oral gavage at 0.3 mg/kg and 1 mg/kg daily.

References