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Purity: ≥98%
Sapanisertib (NK-128; MLN-0128; TAK-228) is a novel, potent, orally bioavailable and selective inhibitor of mTOR (mammalian target of rapamycin) with potential anticancer activity. In cell-free assays, it has an IC50 of 1 nM and inhibits mTOR. INK 128 exhibits tumor growth inhibition efficacy at a dose of 0.3 mg/kg/day in a ZR-75-1 breast cancer xenograft model. In multiplexenograft models, daily oral administration of INK 128 reduces tumor growth and angiogenesis.
| Targets |
mTOR (IC50 = 1 nM); PI3Kα (IC50 = 219 nM); PI3Kγ (IC50 = 221 nM); PI3Kδ (IC50 = 230 nM); PI3Kβ (IC50 = 5.293 μM); mTORC1; mTORC2; Autophagy
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| ln Vitro |
Sapanisertib (INK-128) has an enzymatic inhibitory activity against mTOR and a selectivity for PI3K kinases that is greater than 100-fold[1].
In PC3 cells, sapanisertib (INK-128) specifically reduces the protein-level expression of YB1, MTA1, vimentin, and CD44 but not the transcript level. Sapanisertib (INK-128) reduces the ability of PC3 prostate cancer cells to invade. Additionally, Sapanisertib (INK-128) inhibits the migration of cancer cells beginning at 6 hours after treatment, precisely coinciding with the time at which pro-invasion gene expression is reduced but prior to any alterations in the cell cycle or overall global protein synthesis[2].
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| ln Vivo |
Sapanisertib (INK-128) exhibits tumor growth inhibition efficacy at a dose of 0.3 mg/kg/day in a ZR-75-1 breast cancer xenograft model[1].
In PtenL/L mice, INK128 treatment completely restores 4EBP1 and p70S6K1/2 phosphorylation to wild-type levels. Treatment with sapanisertib (INK-128) reduces PTENL/L mice's prostatic intraepithelial neoplasia (PIN) lesions by 50% and causes programmed cell death in a number of cancer cell lines[2].
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| Enzyme Assay |
Sapanisertib (INK-128) is a ATP-dependentmTOR1/2inhibitor with anIC50of 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.
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| 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) required to achieve a 50% inhibition of cell growth (IC50) is determined using concentrations ranging from 20.0 M to 0.1 nM (12-point curve).
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| Animal Protocol |
A subcutaneous inoculation of 5×106 MDA-MB-361 cells is administered to naked mice in the right subscapular region. The allocation of mice to vehicle control or treatment groups occurs once tumors have grown to a size of 150–200 mm3. Sapanisertib (INK-128) is formulated in 5% polyvinylpropyline, 15% NMP, and 80% water and is given orally by gavage at 0.3 mg/kg and 1 mg/kg daily.
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| References | |
| Additional Infomation |
5-(4-amino-1-propan-2-yl-3-pyrazolo[3,4-d]pyrimidinyl)-1,3-benzoxazol-2-amine is a benzoxazole.
Sapanisertib has been used in trials studying the treatment of HCC, Solid Tumor, Gliosarcoma, Liver Cancer, and Glioblastoma, among others. Sapanisertib is an orally bioavailable inhibitor of raptor-mTOR (TOR complex 1 or TORC1) and rictor-mTOR (TOR complex 2 or TORC2) with potential antineoplastic activity. Sapanisertib 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. TORC1 and 2 are upregulated in some tumors and play an important role in the PI3K/Akt/mTOR signaling pathway, which is frequently dysregulated in human cancers. |
| Molecular Formula |
C15H15N7O
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|---|---|
| Molecular Weight |
309.3259
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| Exact Mass |
309.133
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| Elemental Analysis |
C, 58.24; H, 4.89; N, 31.70; O, 5.17
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| CAS # |
1224844-38-5
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| Related CAS # |
1224844-38-5
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| PubChem CID |
45375953
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| Appearance |
White to off white solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
598.8±60.0 °C at 760 mmHg
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| Flash Point |
315.9±32.9 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.829
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| LogP |
1.95
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
23
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| Complexity |
436
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1C(N([H])[H])=NC2=C1C([H])=C([H])C(=C2[H])C1C2=C(N([H])[H])N=C([H])N=C2N(C([H])(C([H])([H])[H])C([H])([H])[H])N=1
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| InChi Key |
GYLDXIAOMVERTK-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
5-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1,3-benzoxazol-2-amine
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| Synonyms |
MLN-0128; Sapanisertib; TAK-228; TAK 228; TAK228; INK128; INK-128; INK 128; MLN0128; MLN 0128; MLN-0128
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~62 mg/mL (~200.4 mM)
Water: <1 mg/mL Ethanol: ~2 mg/mL (~6.5 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.72 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.72 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (6.72 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 30% PEG400+0.5% Tween80+5% propylene glycol: 30mg/mL |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03047213 | Active Recruiting |
Drug: Sapanisertib | Recurrent Bladder Carcinoma Metastatic Transitional Cell Carcinoma |
National Cancer Institute (NCI) |
August 24, 2017 | Phase 2 |
| NCT02159989 | Active Recruiting |
Drug: Sapanisertib Biological: Ziv-Aflibercept |
Ovarian Carcinoma Fibrolamellar Carcinoma |
National Cancer Institute (NCI) |
June 3, 2014 | Phase 1 |
| NCT02133183 | Active Recruiting |
Drug: Sapanisertib | Glioblastoma Gliosarcoma |
National Cancer Institute (NCI) |
May 12, 2014 | Phase 1 |
| NCT02503722 | Active Recruiting |
Drug: Sapanisertib Drug: Osimertinib |
Metastatic Lung Non-Small Cell Carcinoma Recurrent Lung Non-Small Cell Carcinoma |
National Cancer Institute (NCI) |
October 13, 2016 | Phase 1 |
| NCT02484430 | Active Recruiting |
Drug: Sapanisertib | B Acute Lymphoblastic Leukemia T Acute Lymphoblastic Leukemia |
National Cancer Institute (NCI) |
October 20, 2016 | Phase 2 |
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 ofYB1, MTA1, CD44and vimentin mRNAs in a subset of pre-invasive prostate cancer cellsin vivo.Nature.2012 Feb 22;485(7396):55-61. |
Complete mTOR inhibition by INK128 treatment prevents prostate cancer invasion and metastasisin vivo.Nature.2012 Feb 22;485(7396):55-61. |
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mTOR signal pathway.Drug Discov Today Ther Strateg.2009 Summer;6(2):47-55. |
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