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Description: Sapanisertib (formerly known as INK-128 and MLN-0128) is a novel, potent, orally bioavailable and selective mTOR inhibitor with IC50 of 1 nM in cell-free assays; it displayed >200-fold less potent to class I PI3K isoforms, and is superior in blocking mTORC1/2 and sensitive to pro-invasion genes (vs Rapamycin). INK128 binds to and inhibits both TORC1 and TORC2 complexes of mTOR, which may result in tumor cell apoptosis and a decrease in tumor cell proliferation.
References: Nature. 2012 Feb 22;485(7396):55-61; Drug Discov Today Ther Strateg. 2009; 6(2):47-55.
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
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
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
Purity ≥98%
COA
MSDS
Ribosome profiling reveals mTOR-dependent specialized translational control of the prostate cancer genome. Nature. 2012 Feb 22;485(7396):55-61.
mTOR promotes prostate cancer cell migration and invasion through a translationally regulated gene signature.
TheThe 4EBP1–eIF4E axis controls the post-transcriptional expression of mTOR-sensitive invasion genes. Nature. 2012 Feb 22;485(7396):55-61
mTOR hyperactivation augments translation of YB1, MTA1, CD44 and vimentin mRNAs in a subset of pre-invasive prostate cancer cells in vivo. Nature. 2012 Feb 22;485(7396):55-61.
Complete mTOR inhibition by INK128 treatment prevents prostate cancer invasion and metastasis in vivo. Nature. 2012 Feb 22;485(7396):55-61.
mTOR signal pathway. Drug Discov Today Ther Strateg. 2009 Summer;6(2):47-55.