Sapanisertib (MLN0128)
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MedKoo CAT#: 205495

CAS#: 1224844-38-5

Description: Sapanisertib, also known as TAK-228, MLN0128 and INK128, is a TORC1/2 inhibitor, is also an orally bioavailable inhibitor of raptor-mTOR (TOR complex 1 or TORC1) and rictor-mTOR (TOR complex 2 or TORC2) with potential antineoplastic activity. TORC1/2 inhibitor INK128 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.


Chemical Structure

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Sapanisertib (MLN0128)
CAS# 1224844-38-5

Theoretical Analysis

MedKoo Cat#: 205495
Name: Sapanisertib (MLN0128)
CAS#: 1224844-38-5
Chemical Formula: C15H15N7O
Exact Mass: 309.1338
Molecular Weight: 309.333
Elemental Analysis: C, 58.24; H, 4.89; N, 31.70; O, 5.17

Price and Availability

Size Price Availability Quantity
25.0mg USD 150.0 Ready to ship
50.0mg USD 250.0 Ready to ship
100.0mg USD 450.0 Ready to ship
200.0mg USD 750.0 Ready to ship
500.0mg USD 1650.0 Ready to ship
1.0g USD 2950.0 2 Weeks
2.0g USD 5250.0 2 Weeks
5.0g USD 7950.0 2 Weeks
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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

Biological target: Sapanisertib (INK-128; MLN0128; TAK-228) is an ATP-dependent mTOR1/2 inhibitor with an IC50 of 1 nM for mTOR kinase.
In vitro activity: qRT-PCR analysis of BON treated for 48 hours with 100 nM sapanisertib revealed that sapanisertib decreased TF (tissue factor) mRNA expression (Fig 3A). Western blotting revealed a decrease in the protein levels of flTF and asTF in response to sapanisertib (Fig.3B). Sapanisertib caused a concentration-dependent suppression of 4E-BP1 and Akt activation indicative of a suppression of mTORC1/2 activity. (Fig. 3B). Sapanisertib also caused in increase in Akt phosphorylation at T308 due to relief of mTORC1-mediated feedback inhibition of receptor tyrosine kinase activity. Reference: J Thromb Haemost. 2019 Jan; 17(1): 169–182. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345540/
In vivo activity: To further confirm whether INK128 inhibits the accumulation of glucose-induced MDSC expansion in vivo, STZ (streptozotocin)-induced diabetic mice were treated with vehicle and 1 mg/kg INK128 for 45 days. The percentage of MDSCs in BM (bone marrow), PBMC (peripheral blood mononuclear cell), and spleen was significantly lower in DM (diabetic mice) + INK128 group than that in the DM group both at inflammatory and proliferative phases after injury (Fig. 5c–i; P < 0.05). In INK128-treated diabetic mice, the infiltration of MDSCs in the skin tissue around the wound significantly decreased at inflammatory and proliferative phases after injury through immunofluorescence staining Gr-1 of skin tissue (Fig. 5j, k). Taken together, these results suggested high glucose caused the accumulation of MDSCs in an mTOR-dependent manner and INK128 inhibited the expansion of MDSCs in vitro and in vivo. Reference: Stem Cell Res Ther. 2021; 12: 170. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944919/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 42.17 132.33
DMSO:PBS (pH 7.2) (1:1) 0.5 1.62
DMF 1.0 3.23

Preparing Stock Solutions

The following data is based on the product molecular weight 309.333 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.

Recalculate based on batch purity %
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. 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. 2. Spaeth-Cook D, Burch M, Belton R, Demoret B, Grosenbacher N, David J, Stets C, Cohen D, Shakya R, Hays JL, Chen JL. Loss of TXNIP enhances peritoneal metastasis and can be abrogated by dual TORC1/2 inhibition. Oncotarget. 2018 Nov 2;9(86):35676-35686. doi: 10.18632/oncotarget.26281. PMID: 30479697; PMCID: PMC6235015. 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. 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. 2. Spaeth-Cook D, Burch M, Belton R, Demoret B, Grosenbacher N, David J, Stets C, Cohen D, Shakya R, Hays JL, Chen JL. Loss of TXNIP enhances peritoneal metastasis and can be abrogated by dual TORC1/2 inhibition. Oncotarget. 2018 Nov 2;9(86):35676-35686. doi: 10.18632/oncotarget.26281. PMID: 30479697; PMCID: PMC6235015.
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.

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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.



Additional Information

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).