1. PI3K/Akt/mTOR
    Autophagy
  2. PI3K
    mTOR
    Autophagy

INK-128 (Synonyms: Sapanisertib; MLN0128)

Cat. No.: HY-13328 Purity: 99.55%
Data Sheet SDS Handling Instructions

INK-128 is a potent and selective mTOR inhibitor with IC50 of 1 nM, > 200-fold less potent to class I PI3K isoforms, superior in blocking mTORC1/2 and sensitive to pro-invasion genes.

For research use only. We do not sell to patients.
INK-128 Chemical Structure

INK-128 Chemical Structure

CAS No. : 1224844-38-5

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $88 In-stock
5 mg $80 In-stock
10 mg $100 In-stock
50 mg $250 In-stock
100 mg $450 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Top Publications Citing Use of Products

    INK-128 purchased from MCE. Usage Cited in: J Virol. 2014 Oct;88(20):11872-85.

    Representative Western blot from two independent experiments of p-Akt, p-mTOR, mTOR, p-4EBP1, 4EBP1, eIF4E, c-myc, and MTA1 genes in CNE-1-LMP2A cells treated with Rapamycin (50 nM) or INK-128 (200 nM) for 24 h. The quantification of the Western blot signals are analyzed.

    INK-128 purchased from MCE. Usage Cited in: J Virol. 2014 Oct;88(20):11872-85.

    Confocal analysis of MTA1 (red) and β-catenin (green) expression in CNE-1-LMP2A cells treated with Rapamycin (50 nM) or INK-128 (200 nM) for 24 h. The scale bar represents 10 μm. Immunofluorescence analysis of MTA1 and β-catenin expression reveals that MTA1 is decreased and β-catenin is maintained in the cytoplasm when the cells are treated with INK-128.

    INK-128 purchased from MCE. Usage Cited in: Oncogene. 2015 Mar 26;34(13):1729-35.

    INK-128 ablates phosphorylation of the mTORC1 substrates, 4E-BP1 and S6K.

    INK-128 purchased from MCE. Usage Cited in: Nat Commun. 2017 Jun 8;8:15617.

    Immunoblot analysis of KRAS protein levels in parental (P) and resistant derivatives (R1 and R2) following 4 h treatment with the corresponding inhibitors Rapamycin, AZD2014, MLN0128, BEZ235 and 4EGI-1. Images are cropped for clarity from the same exposure of the same membrane.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    INK-128 is a potent and selective mTOR inhibitor with IC50 of 1 nM, > 200-fold less potent to class I PI3K isoforms, superior in blocking mTORC1/2 and sensitive to pro-invasion genes.

    IC50 & Target

    IC50: 1 nM (mTOR)

    In Vitro

    INK-128 exhibits an enzymatic inhibition activity against mTOR and more than 100-fold selectivity to PI3K kinases[1]. INK128 selectively decreases the expression of YB1, MTA1, vimentin and CD44 at the protein but not transcript level in PC3 cells. INK128 decreases the invasive potential of PC3 prostate cancer cells. Furthermore, INK128 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, 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. INK128 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].

    Clinical Trial
    NCT Number Sponsor Condition Start Date Phase
    NCT01058707 Millennium Pharmaceuticals, Inc.|Takeda Advanced Solid Malignancies January 2010 Phase 1
    NCT02244463 Dana-Farber Cancer Institute|Millennium Pharmaceuticals, Inc. Anaplastic Thyroid Cancer|Thyroid Cancer July 2015 Phase 2
    NCT02719691 University of Colorado, Denver Metastatic Breast Cancer|Solid Tumors May 13, 2016 Phase 1
    NCT02197572 Millennium Pharmaceuticals, Inc.|Takeda Advanced Solid Tumors September 2014 Phase 1
    NCT02514824 Dana-Farber Cancer Institute|Millennium Pharmaceuticals, Inc. Merkel Cell Carcinoma October 2015 Phase 1|Phase 2
    NCT01351350 Millennium Pharmaceuticals, Inc. Advanced Solid Malignancies|Hematologic Malignancies March 2011 Phase 1
    NCT02091531 Memorial Sloan Kettering Cancer Center|Millennium Pharmaceuticals, Inc. Metastatic Castration-Resistant Prostate Cancer March 2014 Phase 2
    NCT01118689 Millennium Pharmaceuticals, Inc. Relapsed Multiple Myeloma|Refractory Multiple Myeloma|Waldenstrom Macroglobulinemia November 2010 Phase 1
    NCT01899053 Millennium Pharmaceuticals, Inc.|Takeda Advanced Nonhematologic Malignancies July 2013 Phase 1
    NCT02575339 Bert O'Neil, MD|Millennium Pharmaceuticals, Inc.|Big Ten Cancer Research Consortium Hepatocellular Carcinoma|Liver Cancer|HCC July 2016 Phase 1|Phase 2
    NCT02412722 Millennium Pharmaceuticals, Inc.|Takeda Non-Hematologic Malignancy March 12, 2015 Phase 1
    NCT02756364 Millennium Pharmaceuticals, Inc.|Takeda Breast Neoplasms June 1, 2016 Phase 2
    NCT02049957 Millennium Pharmaceuticals, Inc.|Takeda Breast Cancer February 18, 2014 Phase 2
    NCT02724020 Millennium Pharmaceuticals, Inc.|Takeda Clear-cell Metastatic Renal Cell Carcinoma June 30, 2016 Phase 2
    NCT02725268 Millennium Pharmaceuticals, Inc.|European Network of Translational Research in Ovarian Cancer - EUTROC|European Network of Individualized Treatment in Endometrial Cancer - ENITEC|Takeda Endometrial Neoplasms April 1, 2016 Phase 2
    NCT02327169 Millennium Pharmaceuticals, Inc.|Takeda Advanced Nonhematologic Malignancies February 2, 2015 Phase 1
    NCT02893930 National Cancer Institute (NCI) Pancreatic Neuroendocrine Tumor G1|Pancreatic Neuroendocrine Tumor G2|Recurrent Pancreatic Neuroendocrine Carcinoma February 1, 2017 Phase 2
    NCT02601209 National Cancer Institute (NCI) High Grade Sarcoma|Metastatic Leiomyosarcoma|Metastatic Malignant Peripheral Nerve Sheath Tumor|Metastatic Synovial Sarcoma|Metastatic Undifferentiated Pleomorphic Sarcoma|Myxofibrosarcoma|Recurrent Leiomyosarcoma|Recurrent Malignant Peripheral Nerve Sheath Tumor|Recurrent Synovial Sarcoma|Recurrent Undifferentiated Pleomorphic Sarcoma|Uterine Corpus Leiomyosarcoma November 30, 2015 Phase 1|Phase 2
    NCT03047213 National Cancer Institute (NCI) Metastatic Transitional Cell Carcinoma|Metastatic Urothelial Carcinoma|Recurrent Bladder Carcinoma|Stage III Bladder Urothelial Carcinoma|Stage IV Bladder Urothelial Carcinoma|TSC1 Gene Mutation|TSC2 Gene Mutation December 1, 2016 Phase 2
    NCT02484430 National Cancer Institute (NCI) Acute Lymphoblastic Leukemia in Remission|Recurrent Adult Acute Lymphoblastic Leukemia|Refractory Adult Acute Lymphoblastic Leukemia October 20, 2016 Phase 2
    NCT02159989 National Cancer Institute (NCI) Advanced Malignant Solid Neoplasm|Metastatic Malignant Solid Neoplasm|Ovarian Carcinoma|Pancreatic Neuroendocrine Tumor|Recurrent Malignant Solid Neoplasm|Unresectable Solid Neoplasm June 3, 2014 Phase 1
    NCT02133183 National Cancer Institute (NCI) Glioblastoma|Gliosarcoma May 12, 2014
    NCT02417701 National Cancer Institute (NCI) Recurrent Squamous Cell Lung Carcinoma|Stage IV Squamous Cell Lung Carcinoma October 2016 Phase 2
    NCT02503722 National Cancer Institute (NCI) Recurrent Non-Small Cell Lung Carcinoma|Stage IIIA Non-Small Cell Lung Cancer AJCC v7|Stage IIIB Non-Small Cell Lung Cancer AJCC v7|Stage IV Non-Small Cell Lung Cancer AJCC v7 October 13, 2016 Phase 1
    NCT02142803 National Cancer Institute (NCI) Adult Glioblastoma|Endometrial Clear Cell Adenocarcinoma|Endometrial Serous Adenocarcinoma|Ovarian Clear Cell Cystadenocarcinoma|Ovarian Endometrioid Adenocarcinoma|Ovarian Mucinous Cystadenocarcinoma|Ovarian Serous Cystadenocarcinoma|Recurrent Fallopian Tube Carcinoma|Recurrent Ovarian Carcinoma|Recurrent Primary Peritoneal Carcinoma|Recurrent Uterine Corpus Carcinoma|Solid Neoplasm|Stage IIIA Fallopian Tube Cancer|Stage IIIA Ovarian Cancer|Stage IIIA Primary Peritoneal Cancer|Stage IIIB Fallop May 20, 2014 Phase 1
    NCT02465060 National Cancer Institute (NCI) Advanced Malignant Solid Neoplasm|Bladder Carcinoma|Breast Carcinoma|Cervical Carcinoma|Colon Carcinoma|Colorectal Carcinoma|Endometrial Carcinoma|Esophageal Carcinoma|Gastric Carcinoma|Glioma|Head and Neck Carcinoma|Kidney Carcinoma|Liver and Intrahepatic Bile Duct Carcinoma|Lung Carcinoma|Lymphoma|Malignant Uterine Neoplasm|Melanoma|Ovarian Carcinoma|Pancreatic Carcinoma|Plasma Cell Myeloma|Prostate Carcinoma|Rectal Carcinoma|Recurrent Bladder Carcinoma|Recurrent Breast Carcinoma|Recurrent Cer August 12, 2015 Phase 2
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    References
    Preparing Stock Solutions
    Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
    1 mM 3.2328 mL 16.1640 mL 32.3279 mL
    5 mM 0.6466 mL 3.2328 mL 6.4656 mL
    10 mM 0.3233 mL 1.6164 mL 3.2328 mL
    Kinase Assay
    [2]

    mTOR activity is assayed using LanthaScreen Kinase kit reagents. PI(3)K α, β, γ and δ activity are assayed using the PI(3)K HTRF assay kit. The concentration of INK128 necessary to achieve inhibition of enzyme activity by 50% (IC50) is calculated using concentrations ranging from 20 μM to 0.1 nM (12-point curve). IC50 values are determined using a nonlinear regression model. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [2]

    PC3 cells are treated with the appropriate drug for 48 h, and proliferation is measured using CellTiter-Glo Luminescent reagent. The concentration of INK128 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). MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2]

    INK128 is formulated in 5% polyvinylpropyline, 15% NMP, 80% water.

    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. INK128 is formulated in 5% polyvinylpropyline, 15% NMP, 80% water and administered by oral gavage at 0.3 mg/kg and 1 mg/kg daily. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    M.Wt

    309.33

    Formula

    C₁₅H₁₅N₇O

    CAS No.

    1224844-38-5

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    10 mM in DMSO

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    Purity: 99.55%

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    Product Name:
    INK-128
    Cat. No.:
    HY-13328
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