Sapanisertib | TAK-228 | INK-128 | MLN0128 | CAS#1224844-38-5 | mTOR Inhibitor

MedKoo Cat#: 205495 | Name: Sapanisertib (MLN0128)

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

Sapanisertib (MLN0128)

CAS#1224844-38-5 (free base)

Theoretical Analysis

MedKoo Cat#: 205495

Name: Sapanisertib (MLN0128)

CAS#: 1224844-38-5 (free base)

Chemical Formula: C15H15N7O

Exact Mass: 309.1338

Molecular Weight: 309.33

Elemental Analysis: C, 58.24; H, 4.89; N, 31.70; O, 5.17

Price and Availability

Size	Price	Availability
10mg	USD 110.00	Ready to ship
25mg	USD 220.00	Ready to ship
50mg	USD 385.00	Ready to ship
100mg	USD 600.00	Ready to ship
200mg	USD 950.00	Ready to ship
500mg	USD 2,050.00	2-3 weeks
1g	USD 3,850.00	2-3 weeks

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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).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#TZC50826

QC Data

View QC data: current batch, Lot#TZC50826

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMSO	42.2	132.33
	DMSO:PBS (pH 7.2) (1:1)	0.5	1.62
	DMF	1.0	3.23

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

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:

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: Sehgal K, Serritella A, Liu M, ONeill A, Nangia C, Pappa T, Demeure MJ, Worden FP, Haddad R, Lorch J. A phase I/II trial of sapanisertib in advanced anaplastic and radioiodine refractory differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2024 Jun 29:dgae443. doi: 10.1210/clinem/dgae443. Epub ahead of print. PMID: 38943664. 2: Bellmunt J, Maroto P, Bonfill T, Vazquez F, Perez-Gracia JL, Juanpere N, Hernandez-Prat A, Hernandez-Llodra S, Rovira A, Juan O, Rodriguez-Vida A. Dual mTOR1/2 Inhibitor Sapanisertib (FTH-003/TAK-228) in Combination With Weekly Paclitaxel in Patients With Previously Treated Metastatic Urothelial Carcinoma: A Phase II Open-Label Study. Clin Genitourin Cancer. 2024 Oct;22(5):102123. doi: 10.1016/j.clgc.2024.102123. Epub 2024 May 23. PMID: 38905731. 3: Davis SL, Messersmith WA, Purcell WT, Lam ET, Corr BR, Leal AD, Lieu CH, O'Bryant CL, Smoots SG, Dus ED, Jordan KR, Serkova NJ, Pitts TM, Diamond JR. A Phase Ib Expansion Cohort Evaluating Aurora A Kinase Inhibitor Alisertib and Dual TORC1/2 Inhibitor Sapanisertib in Patients with Advanced Solid Tumors. Cancers (Basel). 2024 Apr 10;16(8):1456. doi: 10.3390/cancers16081456. PMID: 38672538; PMCID: PMC11048245. 4: Kadiyala GN, Telwatte S, Wedrychowski A, Janssens J, Kim SJ, Kim P, Deeks S, Wong JK, Yukl SA. Differential susceptibility of cells infected with defective and intact HIV proviruses to killing by obatoclax and other small molecules. AIDS. 2024 Jul 15;38(9):1281-1291. doi: 10.1097/QAD.0000000000003908. Epub 2024 Apr 20. PMID: 38626436; PMCID: PMC11216394. 5: Mirzaie M, Gholizadeh E, Miettinen JJ, Ianevski F, Ruokoranta T, Saarela J, Manninen M, Miettinen S, Heckman CA, Jafari M. Designing patient-oriented combination therapies for acute myeloid leukemia based on efficacy/toxicity integration and bipartite network modeling. Oncogenesis. 2024 Mar 1;13(1):11. doi: 10.1038/s41389-024-00510-9. PMID: 38429288; PMCID: PMC10907624. 6: Kalla C, Ott G, Finotello F, Niewola-Staszkowska K, Conza GD, Lahn M, van der Veen L, Schüler J, Falkenstern-Ge R, Kopecka J, Riganti C. The highly selective and oral phosphoinositide 3-kinase delta (PI3K-δ) inhibitor roginolisib induces apoptosis in mesothelioma cells and increases immune effector cell composition. Transl Oncol. 2024 May;43:101857. doi: 10.1016/j.tranon.2023.101857. Epub 2024 Feb 27. PMID: 38412661; PMCID: PMC10907864. 7: Coleman N, Stephen B, Fu S, Karp D, Subbiah V, Ahnert JR, Piha-Paul SA, Wright J, Fessahaye SN, Ouyang F, Yilmaz B, Meric-Bernstam F, Naing A. Phase I study of sapanisertib (CB-228/TAK-228/MLN0128) in combination with ziv- aflibercept in patients with advanced solid tumors. Cancer Med. 2024 Feb;13(3):e6877. doi: 10.1002/cam4.6877. PMID: 38400671; PMCID: PMC10891443. 8: Klieber N, Hildebrand LS, Faulhaber E, Symank J, Häck N, Härtl A, Fietkau R, Distel LV. Different Impacts of DNA-PK and mTOR Kinase Inhibitors in Combination with Ionizing Radiation on HNSCC and Normal Tissue Cells. Cells. 2024 Feb 6;13(4):304. doi: 10.3390/cells13040304. PMID: 38391917; PMCID: PMC10887161. 9: Subbiah V, Coleman N, Piha-Paul SA, Tsimberidou AM, Janku F, Rodon J, Pant S, Dumbrava EEI, Fu S, Hong DS, Zhang S, Sun M, Jiang Y, Roszik J, Song J, Yuan Y, Meric-Bernstam F, Naing A. Phase I Study of mTORC1/2 Inhibitor Sapanisertib (CB-228/TAK-228) in Combination with Metformin in Patients with mTOR/AKT/PI3K Pathway Alterations and Advanced Solid Malignancies. Cancer Res Commun. 2024 Feb 12;4(2):378-387. doi: 10.1158/2767-9764.CRC-22-0260. PMID: 38126764; PMCID: PMC10860536. 10: Wu Y, Chen S, Yang X, Sato K, Lal P, Wang Y, Shinkle AT, Wendl MC, Primeau TM, Zhao Y, Gould A, Sun H, Mudd JL, Hoog J, Mashl RJ, Wyczalkowski MA, Mo CK, Liu R, Herndon JM, Davies SR, Liu D, Ding X, Evrard YA, Welm BE, Lum D, Koh MY, Welm AL, Chuang JH, Moscow JA, Meric-Bernstam F, Govindan R, Li S, Hsieh J, Fields RC, Lim KH, Ma CX, Zhang H, Ding L, Chen F. Combining the Tyrosine Kinase Inhibitor Cabozantinib and the mTORC1/2 Inhibitor Sapanisertib Blocks ERK Pathway Activity and Suppresses Tumor Growth in Renal Cell Carcinoma. Cancer Res. 2023 Dec 15;83(24):4161-4178. doi: 10.1158/0008-5472.CAN-23-0604. PMID: 38098449; PMCID: PMC10722140. 11: Al-Kali A, Aldoss I, Atherton PJ, Strand CA, Shah B, Webster J, Bhatnagar B, Flatten KS, Peterson KL, Schneider PA, Buhrow SA, Kong J, Reid JM, Adjei AA, Kaufmann SH. A phase 2 and pharmacological study of sapanisertib in patients with relapsed and/or refractory acute lymphoblastic leukemia. Cancer Med. 2023 Dec;12(23):21229-21239. doi: 10.1002/cam4.6701. Epub 2023 Nov 13. PMID: 37960985; PMCID: PMC10726920. 12: Han SN, Oza A, Colombo N, Oaknin A, Raspagliesi F, Wenham RM, Braicu EI, Jewell A, Makker V, Krell J, Alía EMG, Baurain JF, Su Z, Neuwirth R, Vincent S, Sedarati F, Faller DV, Scambia G. A randomized phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer. Gynecol Oncol. 2023 Nov;178:110-118. doi: 10.1016/j.ygyno.2023.09.013. Epub 2023 Oct 14. PMID: 37839313; PMCID: PMC11100409. 13: 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. 14: Lisi L, Pizzoferrato M, Ciotti GMP, Martire M, Navarra P. mTOR Inhibition Is Effective against Growth, Survival and Migration, but Not against Microglia Activation in Preclinical Glioma Models. Int J Mol Sci. 2023 Jun 7;24(12):9834. doi: 10.3390/ijms24129834. PMID: 37372982; PMCID: PMC10297872. 15: Goodstein T, Yang Y, Runcie K, Srinivasan R, Singer EA. Two is company, is three a crowd? Triplet therapy, novel molecular targets, and updates on the management of advanced renal cell carcinoma. Curr Opin Oncol. 2023 May 1;35(3):206-217. doi: 10.1097/CCO.0000000000000939. PMID: 37226958; PMCID: PMC10213993. 16: Alhalabi O, Groisberg R, Zinner R, Hahn AW, Naing A, Zhang S, Tsimberidou AM, Rodon J, Fu S, Yap TA, Hong DS, Sun M, Jiang Y, Pant S, Shah AY, Zurita A, Tannir NM, Vikram R, Roszik J, Meric-Bernstam F, Subbiah V. Phase I study of sapanisertib with carboplatin and paclitaxel in mTOR pathway altered solid malignancies. NPJ Precis Oncol. 2023 Apr 18;7(1):37. doi: 10.1038/s41698-023-00369-w. PMID: 37072571; PMCID: PMC10113233. 17: Wei BR, Peer CJ, Richardson WJ, Hewitt SM, Figg WD, Simpson RM. Pharmacokinetics and tolerability of the dual TORC1/2 inhibitor sapanisertib in combination with the MEK inhibitor trametinib in dogs. Front Vet Sci. 2022 Dec 14;9:1056408. doi: 10.3389/fvets.2022.1056408. PMID: 36590793; PMCID: PMC9794608. 18: Crunkhorn S. Repurposing sapanisertib in malaria. Nat Rev Drug Discov. 2022 Dec;21(12):880. doi: 10.1038/d41573-022-00183-2. PMID: 36323854. 19: Gunder LC, Moyer TH, Johnson HR, Auyeung AS, Leverson GE, Zhang W, Matkowskyj KA, Carchman EH. Anal Cancer Prevention Through the Topical Use of Single or Dual PI3K/mTOR Inhibitors. J Surg Res. 2023 Feb;282:137-146. doi: 10.1016/j.jss.2022.09.025. Epub 2022 Oct 20. PMID: 36274448. 20: Rajdev L, Lee JW, Libutti SK, Benson AB, Fisher GA Jr, Kunz PL, Hendifar AE, Catalano P, O'Dwyer PJ. A phase II study of sapanisertib (TAK-228) a mTORC1/2 inhibitor in rapalog-resistant advanced pancreatic neuroendocrine tumors (PNET): ECOG-ACRIN EA2161. Invest New Drugs. 2022 Dec;40(6):1306-1314. doi: 10.1007/s10637-022-01311-w. Epub 2022 Oct 20. PMID: 36264382; PMCID: PMC9795724.

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.