WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H205495
CAS#: 1224844-38-5 (free base)
Description: Sapanisertib, also known as TAK-228, MLN0128 and INK128, is a TORC1/2 inhibitor, 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, which may result in tumor cell apoptosis and a decrease in tumor cell proliferation.
Hodoodo Cat#: H205495
Name: Sapanisertib (MLN0128)
CAS#: 1224844-38-5 (free base)
Chemical Formula: C15H15N7O
Exact Mass: 309.13
Molecular Weight: 309.333
Elemental Analysis: C, 58.24; H, 4.89; N, 31.70; O, 5.17
Related CAS #: 1422006-47-0 (monophosphate) 1224844-38-5 (free base) 1422006-46-9 (HCl) 1422006-35-6 (2HCl)
Synonym: TAK-228; TAK 228; TAK228; INK128; INK-128; INK 128; MLN0128; MLN 0128; MLN-0128; Sapanisertib.
IUPAC/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
Appearance: White to off white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info: NK128 is an orally-available, potent and selective TORC1/2 inhibitor. INK128 has demonstrated broad preclinical anti-tumor activity against a range of solid tumor types. Potent inhibition was observed in cell lines resistant to rapamycin and pan-PI3K inhibitors. Unlike other drugs targeting this pathway, INK128 inhibits the kinase activity associated with both the TORC1 and TORC2 complexes of the mTOR kinase. This dual TORC1 and TORC2 activity differentiates INK128 from rapamycin and various related analogs, or rapalogs, which only interfere with TORC1 activity, allowing for feedback loops that may actually augment tumor growth. In contrast, inhibition of both TORC1 and TORC2 may allow for improved efficacy and ultimately greater therapeutic potential for patient benefit. (source: http://www.intellikine.com/pipeline/ink128.html).
Biological target: | Sapanisertib is an ATP-dependent mTOR1/2 inhibitor with an IC50 of 1 nM for mTOR kinase. |
In vitro activity: | Sapanisertib alleviates pulmonary fibrosis by targeting Wnt5a/mTOR/HIF-1α/p70S6K. In TGF-β1-treated A549 cells, sapanisertib suppresses epithelial-mesenchymal transition, increasing E-cadherin and reducing vimentin expression. In L929 cells exposed to TGF-β1, sapanisertib inhibits cell proliferation, decreases collagens I and III, smooth muscle actin, and key proteins like hypoxia-inducing factor, mTOR, p70S6K, and Wnt5a. Reference: Basic Clin Pharmacol Toxicol. 2023 Sep;133(3):226-236. https://pubmed.ncbi.nlm.nih.gov/37394756/ |
In vivo activity: | Sapanisertib has potential to be developed as a clinical strategy to promote wound healing of diabetic patients. Sapanisertib could promote wound healing through reducing the myeloid-derived suppressor cells (MDSCs). MDSC function was disordered in diabetic mice and high-glucose environments, while sapanisertib could help retrieve their function. Reference: Stem Cell Res Ther. 2021; 12: 170. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944919/ |
Solvent | Max Conc. mg/mL | Max Conc. mM | |
---|---|---|---|
Solubility | |||
DMSO | 42.2 | 132.33 | |
DMSO:PBS (pH 7.2) (1:1) | 0.5 | 1.62 | |
DMF | 1.0 | 3.23 |
The following data is based on the product molecular weight 309.33 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
---|---|---|---|
1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
Formulation protocol: | 1. Xu Z, Lv Y, Kong D, Jiang W. Sapanisertib attenuates pulmonary fibrosis by modulating Wnt5a/mTOR signalling. Basic Clin Pharmacol Toxicol. 2023 Sep;133(3):226-236. doi: 10.1111/bcpt.13924. Epub 2023 Jul 20. PMID: 37394756. 2. Lewis CS, Elnakat Thomas H, Orr-Asman MA, Green LC, Boody RE, Matiash K, Karve A, Hisada YM, Davis HW, Qi X, Mercer CA, Lucas FV, Aronow BJ, Mackman N, Versteeg HH, Bogdanov VY. mTOR kinase inhibition reduces tissue factor expression and growth of pancreatic neuroendocrine tumors. J Thromb Haemost. 2019 Jan;17(1):169-182. doi: 10.1111/jth.14342. Epub 2018 Dec 25. PMID: 30472780; PMCID: PMC6345540. 3. Li Y, Xu Y, Liu X, Yan X, Lin Y, Tan Q, Hou Y. mTOR inhibitor INK128 promotes wound healing by regulating MDSCs. Stem Cell Res Ther. 2021 Mar 10;12(1):170. doi: 10.1186/s13287-021-02206-y. PMID: 33691762; PMCID: PMC7944919. 4. Heng D, Sheng X, Tian C, Li J, Liu L, Gou M, Liu L. Mtor inhibition by INK128 extends functions of the ovary reconstituted from germline stem cells in aging and premature aging mice. Aging Cell. 2021 Feb;20(2):e13304. doi: 10.1111/acel.13304. Epub 2021 Jan 14. PMID: 33448083; PMCID: PMC7884035. |
In vitro protocol: | 1. Xu Z, Lv Y, Kong D, Jiang W. Sapanisertib attenuates pulmonary fibrosis by modulating Wnt5a/mTOR signalling. Basic Clin Pharmacol Toxicol. 2023 Sep;133(3):226-236. doi: 10.1111/bcpt.13924. Epub 2023 Jul 20. PMID: 37394756. 2. Lewis CS, Elnakat Thomas H, Orr-Asman MA, Green LC, Boody RE, Matiash K, Karve A, Hisada YM, Davis HW, Qi X, Mercer CA, Lucas FV, Aronow BJ, Mackman N, Versteeg HH, Bogdanov VY. mTOR kinase inhibition reduces tissue factor expression and growth of pancreatic neuroendocrine tumors. J Thromb Haemost. 2019 Jan;17(1):169-182. doi: 10.1111/jth.14342. Epub 2018 Dec 25. PMID: 30472780; PMCID: PMC6345540. |
In vivo protocol: | 1. Li Y, Xu Y, Liu X, Yan X, Lin Y, Tan Q, Hou Y. mTOR inhibitor INK128 promotes wound healing by regulating MDSCs. Stem Cell Res Ther. 2021 Mar 10;12(1):170. doi: 10.1186/s13287-021-02206-y. PMID: 33691762; PMCID: PMC7944919. 2. Heng D, Sheng X, Tian C, Li J, Liu L, Gou M, Liu L. Mtor inhibition by INK128 extends functions of the ovary reconstituted from germline stem cells in aging and premature aging mice. Aging Cell. 2021 Feb;20(2):e13304. doi: 10.1111/acel.13304. Epub 2021 Jan 14. PMID: 33448083; PMCID: PMC7884035. |
1: Maiso P, Liu Y, Morgan B, Azab A, Ren P, Martin MB, Zhang Y, Liu Y, Sacco A, Ngo H, Azab F, Quang P, Rodig SJ, Lin CP, Roccaro A, Rommel C, Ghobrial IM. Defining the role of TORC1 and TORC2 in multiple myeloma. Blood. 2011 Nov 1. [Epub ahead of print] PubMed PMID: 22045983.
1. Lim C, Dismuke T, Malawsky D, Ramsey JD, Hwang D, Godfrey VL, Kabanov AV, Gershon TR, Sokolsky-Papkov M. Enhancing CDK4/6 inhibitor therapy for medulloblastoma using nanoparticle delivery and scRNA-seq-guided combination with sapanisertib. Sci Adv. 2022 Jan 28;8(4):eabl5838. doi: 10.1126/sciadv.abl5838. Epub 2022 Jan 26. PMID: 35080986; PMCID: PMC8791615.