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Sapanisertib (MLN0128)

For research use only.

Catalog No.S2811 Synonyms: INK 128,TAK-228

77 publications

Sapanisertib (MLN0128) Chemical Structure

CAS No. 1224844-38-5

Sapanisertib (MLN0128, INK 128, TAK-228) is a potent and selective mTOR inhibitor with IC50 of 1 nM in cell-free assays; >200-fold less potent to class I PI3K isoforms, superior in blocking mTORC1/2 and sensitive to pro-invasion genes (vs Rapamycin). Phase 1.

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Selleck's Sapanisertib (MLN0128) has been cited by 77 publications

Purity & Quality Control

Choose Selective mTOR Inhibitors

Biological Activity

Description Sapanisertib (MLN0128, INK 128, TAK-228) is a potent and selective mTOR inhibitor with IC50 of 1 nM in cell-free assays; >200-fold less potent to class I PI3K isoforms, superior in blocking mTORC1/2 and sensitive to pro-invasion genes (vs Rapamycin). Phase 1.
Targets
mTOR [3]
(Cell-free assay)
mTOR [3]
(Cell-free assay)
PI3Kα [3]
(Cell-free assay)
PI3Kγ [3]
(Cell-free assay)
PI3Kδ [3]
(Cell-free assay)
1.4 nM(Ki) 1.4 nM(Ki) 219 nM 221 nM 230 nM
In vitro

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

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
PANC-1  Mn7ISpVv[3Srb36gRZN{[Xl? NVLOSWt1OTBibl2= NF7ieVA4OiCq NWrPSoxWcW6lcnXhd4V{KGenbXPpeIFjcW6nIIPlcpNqfGm4aYT5 NU\HSIFCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5O|E2PDRpPkK0PVcyPTR2PD;hQi=>
PANC-1  MlP0SpVv[3Srb36gRZN{[Xl? MX:1NEBvVQ>? NFHPPZA1QCCq NH3TT3NlcXO{dYD0d{Bk\WyuIHP5Z4xmKHC{b3fy[ZN{cW:w MmLuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7N{G1OFQoRjJ2OUexOVQ1RC:jPh?=
PANC-1  M3r3W2Z2dmO2aX;uJGF{e2G7 M4rqdlExNzVyIH7N NYTjXWlIOjRiaB?= MoOw[JJidWG2aXPhcIx6KGmwaHnibZR{KHCqb4PwbI9zgWyjdHnvckBw\iB2RT3CVFEuWz[NMTCocXRQWkNzIHHjeIl3[XSrb36gbY5lcWOjdH;yd{kh[W6mIFHreEBifCCVZYKgOFc{KCi2aHWgcXRQWkN{IHHjeIl3[XSrb36gbY5lcWOjdH;yLS=> M4ryZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUexOVQ1Lz5{NEm3NVU1PDxxYU6=
PANC-1  NVf6V3NLSXCxcITvd4l{KEG|c3H5 NVHKWmx4OTBvMUCwJI5O NXfTSFk6PzJiaB?= M17PWIlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= NXvtZlBJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5O|E2PDRpPkK0PVcyPTR2PD;hQi=>
MIA PaCa-2 NVHFSI1tS2WubDDWbYFjcWyrdImgRZN{[Xl? M3PFZ|EuOTByIH7N NFzCNnM4OiCq MUDpcohq[mm2czDj[YxtKH[rYXLpcIl1gSCmb4PlJIRmeGWwZHXueIx6 M{f3d|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUexOVQ1Lz5{NEm3NVU1PDxxYU6=
PANC-1  MojFR4VtdCCYaXHibYxqfHliQYPzZZk> NV\0eFVlPTBibl2= M3TLR|I1NTl4IHi= M4XSN4lvcGmkaYTzJINmdGxidnnhZoltcXS7IITpcYUh\GWyZX7k[Y51dHl? NYDOcnk3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5O|E2PDRpPkK0PVcyPTR2PD;hQi=>
PANC-1  NEC1OHVE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M4LRb|EuOTByIH7N NXrwWoJOPzJiaB?= MXjpcohq[mm2czDj[YxtKH[rYXLpcIl1gSCmb4PlJIRmeGWwZHXueIx6 M3TjWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUexOVQ1Lz5{NEm3NVU1PDxxYU6=
TC32 MnTvdWhVWyCjc4PhfS=> MnzkdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKFSFM{KgZ4VtdHN? MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
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SK-N-SH NXrBcIg4eUiWUzDhd5NigQ>? MXfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0tvTj3TTEBk\Wyucx?= MlO0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
BT-12 NF73[4JyUFSVIHHzd4F6 NYrnSFFOeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFLUMVEzKGOnbHzz Ml\UQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
MG 63 (6-TG R) NHTYe5RyUFSVIHHzd4F6 MUHxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVUdiNkOgLFYuXEdiUjmgZ4VtdHN? M{f6UlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
BT-12 M1;EO5FJXFNiYYPzZZk> NWO1fHJVeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhSlRvMUKgZ4VtdHN? NInYPGk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
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LAN-5 NFjjUnRyUFSVIHHzd4F6 M4XvPJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJGxCVi13IHPlcIx{ M2HMXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
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... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-4EBP1 / 4EBP1 / p-S6 / S6 / p-Akt-S473 / p-Akt-T308 / Akt; 

PubMed: 25425103     


INK128 inhibits mTOR signaling in neuroblastoma cells. A panel of six neuroblastoma cell lines was treated with 0.2 μM INK128 for 0 hr, 4 hrs, and 6 hrs, lysed, subjected to SDS-PAGE and immunoblotted with indicated antibodies. β-Actin was detected as a l䲧疝Ỵ疞㧀疜膉痘 瘿뙠ෆᾰƌෆĀ

CD44 / Vimentin; 

PubMed: 29899840     


CD44 (high) SNU423 cells were treated with increasing concentrations of INK128 for 48 h. CD44, vimentin and downstream effectors of mTOR pathway were evaluated by immunoblotting. 

c-Jun; 

PubMed: 27462815     


Representative western blot of 293T cells after 24 h treatment with INK128. The results are representative of three independent experiments. 

p-mTOR(Ser2448) / mTOR / p-p70S6K(Thr389) / p70S6K / p-RPS / RPS6; 

PubMed: 25849580     


SUDHL-2 and SUDHL-4 cells were treated with either EtOH for 24 h, INK128 for 3 h at the concentrations as indicated, or 20 nM rapamycin (Rap.) for 3 h. Cell lysates were analyzed by western blotting for phosphorylation states and total levels of indicated䲧疝Ỵ疞㧀疜

FKBP1 / MARS / CDC25A / TCL1A; 

PubMed: 25849580     


SUDHL-2 and SUDHL-4 cells are treated with EtOH (20 mM) for 48 h or INK128 (40 nM) for 24 h. Protein levels of validated genes were analyzed by western blotting.

25425103 29899840 27462815 25849580
Growth inhibition assay
Cell viability ; 

PubMed: 25425103     


Six neuroblastoma cell lines were treated with the indicated concentrations of INK128 for 48 hrs. Cell viability was then measured by adding the mixture of 10 μL of CCK-8 and 190 μL of RPMI 1640 and reading the absorbance at 450 nm. Data were represented 䲧疝Ỵ疞㧀疜膉痘 瘿뙠ෆᾰƌෆĀ 㺣痖帉痖Ѐ瑖堘𢡄빢᎒ෆĀ鑸᎒彿堙奋堙巫堙᎒ﻺ᎒彿堙ﻮ᎒塚堙ﻺ

25425103
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. [1] Daily, oral administration of INK 128 inhibits angiogenesis and tumor growth in multiplexenograft models. [2]

Protocol

Solubility (25°C)

In vitro DMSO 62 mg/mL (200.43 mM)
Ethanol 2 mg/mL (6.46 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
30% PEG400+0.5% Tween80+5% propylene glycol
For best results, use promptly after mixing.
30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 309.33
Formula

C15H15N7O

CAS No. 1224844-38-5
Storage powder
in solvent
Synonyms INK 128,TAK-228
Smiles CC(C)N1C2=NC=NC(=C2C(=N1)C3=CC4=C(C=C3)OC(=N4)N)N

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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% DMSO % % Tween 80 % ddH2O
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Bio Calculators

Molarity Calculator

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Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

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Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

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* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04250545 Recruiting Drug: Sapanisertib|Drug: Telaglenastat Hydrochloride Leptomeningeal Neoplasm|Metastatic Lung Non-Small Cell Carcinoma|Metastatic Malignant Neoplasm in the Brain|Recurrent Lung Non-Small Cell Carcinoma|Stage IV Lung Cancer AJCC v8|Stage IVA Lung Cancer AJCC v8|Stage IVB Lung Cancer AJCC v8 National Cancer Institute (NCI) June 12 2020 Phase 1
NCT02575339 Active not recruiting Drug: MLN0128|Drug: MLN0128 (RP2D)|Drug: Sorafenib Hepatocellular Carcinoma|Liver Cancer|HCC Kathy Miller|Millennium Pharmaceuticals Inc.|Big Ten Cancer Research Consortium July 2016 Phase 1|Phase 2
NCT02719691 Active not recruiting Drug: Alisertib|Drug: MLN0128 Metastatic Breast Cancer|Solid Tumors University of Colorado Denver May 13 2016 Phase 1
NCT02514824 Completed Drug: MLN0128 Merkel Cell Carcinoma Dana-Farber Cancer Institute|Millennium Pharmaceuticals Inc. October 2015 Phase 1|Phase 2
NCT02244463 Recruiting Drug: MLN0128 Anaplastic Thyroid Cancer|Thyroid Cancer Dana-Farber Cancer Institute|Millennium Pharmaceuticals Inc. July 2015 Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Frequently Asked Questions

  • Question 1:

    What is the recommendation method to formulate S2811 INK 128 (MLN0128) for oral administration?

  • Answer:

    You can try this vehicle for oral administration: 30% PEG400+0.5% Tween80 +5% Propylene glycol.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID