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Sapanisertib (MLN0128)

Names

[ CAS No. ]:
1224844-38-5

[ Name ]:
Sapanisertib (MLN0128)

[Synonym ]:
cs-0557
2-Benzoxazolamine, 5-[4-amino-1-(1-methylethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-
UNII-JGH0DF1U03
3-(2-Amino-1,3-benzoxazol-5-yl)-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine
Sapanisertib
ink-128/ink128
MLN-0128
ink 128
UNII:JGH0DF1U03
INK-128

Biological Activity

[Description]:

Sapanisertib (INK-128) is a ATP-dependent mTOR1/2 inhibitor with an IC50 of 1 nM for mTOR kinase.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy
Signaling Pathways >> PI3K/Akt/mTOR >> mTOR
Research Areas >> Cancer

[Target]

mTOR:1 nM (IC50)

mTORC1

mTORC2

PI3Kα:219 nM (IC50)

PI3Kβ:5.293 μM (IC50)

PI3Kδ:230 nM (IC50)

PI3Kγ:221 nM (IC50)

Autophagy


[In Vitro]

Sapanisertib (INK-128) exhibits an enzymatic inhibition activity against mTOR and more than 100-fold selectivity to PI3K kinases[1]. 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[2].

[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[1]. 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[2].

[Cell Assay]

PC3 cells are treated with the appropriate drug for 48 h, and proliferation is measured using CellTiter-Glo Luminescent reagent. The concentration of Sapanisertib (INK-128) necessary to achieve inhibition of cell growth by 50% (IC50) is calculated using concentrations ranging from 20.0 μM to 0.1 nM (12-point curve).

[Animal admin]

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]

[1]. Liu A, et al. mTOR Mediated Anti-Cancer Drug Discovery. Drug Discovery Today: Therapeutic Strategies. 2009, 6(2), 47-55.

[2]. Hsieh AC, et al. The translational landscape of mTOR signalling steers cancer initiation and metastasis. Nature. 2012 Feb 22;485(7396):55-61.


[Related Small Molecules]

Rapamycin (Sirolimus) | Torin 1 | MHY1485 | AZD8055 | Dactolisib (BEZ235) | Vistusertib (AZD2014) | Torkinib (PP242) | LY3023414 | Torin 2 | GSK2126458(GSK458) | PF-04691502 | Salidroside | PQR-309 | OSI-027 | PI-103

Chemical & Physical Properties

[ Density]:
1.6±0.1 g/cm3

[ Boiling Point ]:
598.8±60.0 °C at 760 mmHg

[ Molecular Formula ]:
C15H15N7O

[ Molecular Weight ]:
309.326

[ Flash Point ]:
315.9±32.9 °C

[ Exact Mass ]:
309.133820

[ PSA ]:
121.67000

[ LogP ]:
1.95

[ Vapour Pressure ]:
0.0±1.7 mmHg at 25°C

[ Index of Refraction ]:
1.829

[ Storage condition ]:
-20°C

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Related Compounds