WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H202870
CAS#: 162635-04-3
Description: Temsirolimus is an ester analog of rapamycin. Temsirolimus binds to and inhibits the mammalian target of rapamycin (mTOR), resulting in decreased expression of mRNAs necessary for cell cycle progression and arresting cells in the G1 phase of the cell cycle. mTOR is a serine/threonine kinase which plays a role in the PI3K/AKT pathway that is upregulated in some tumors. Temsirolimus (CCI-779) is an intravenous drug for the treatment of renal cell carcinoma (RCC), developed by Wyeth Pharmaceuticals and approved by the U.S. Food and Drug Administration (FDA) in late May 2007, and was also approved by the European Medicines Agency (EMEA) on November 2007.
Hodoodo Cat#: H202870
Name: Temsirolimus
CAS#: 162635-04-3
Chemical Formula: C56H87NO16
Exact Mass: 1,029.60
Molecular Weight: 1,030.290
Elemental Analysis: C, 65.28; H, 8.51; N, 1.36; O, 24.85
Synonym: CCI779; CCI-779; CCI 779; Temsirolimus; US brand name: Torisel.
IUPAC/Chemical Name: (1R,2R,4S)-4-{(2R)-2-[(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-1,5,11,28,29-pentaoxo-1,4,5,6,9,10,11,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontin-3-yl]propyl}-2-methoxycyclohexyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate.
InChi Key: CBPNZQVSJQDFBE-FUXHJELOSA-N
InChi Code: InChI=1S/C56H87NO16/c1-33-17-13-12-14-18-34(2)45(68-9)29-41-22-20-39(7)56(67,73-41)51(63)52(64)57-24-16-15-19-42(57)53(65)71-46(30-43(60)35(3)26-38(6)49(62)50(70-11)48(61)37(5)25-33)36(4)27-40-21-23-44(47(28-40)69-10)72-54(66)55(8,31-58)32-59/h12-14,17-18,26,33,35-37,39-42,44-47,49-50,58-59,62,67H,15-16,19-25,27-32H2,1-11H3/b14-12+,17-13+,34-18+,38-26+/t33-,35-,36-,37-,39-,40+,41+,42+,44-,45+,46+,47-,49-,50+,56-/m1/s1
SMILES Code: O=C(O[C@H]1[C@H](OC)C[C@H](C[C@H]([C@@H](OC([C@@](CCCC2)([H])N2C(C([C@@]3(O)[C@H](C)CC[C@@](O3)([H])C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C([C@H](OC)[C@H](O)/C(C)=C/[C@H]4C)=O)=O)=O)=O)CC4=O)C)CC1)C(C)(CO)CO
Appearance: 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: Temsirolimus (CCI-779) is an intravenous drug for the treatment of renal cell carcinoma (RCC), developed by Wyeth Pharmaceuticals and approved by the U.S. Food and Drug Administration (FDA) in late May 2007, and was also approved by the European Medicines Agency (EMEA) on November 2007. It is a derivative of sirolimus and is sold as Torisel. mTOR (mammalian target of rapamycin) is a kinase enzyme inside the cell that collects and interprets the numerous and varied growth and survival signals received by tumor cells. When the kinase activity of mTOR is activated, its downstream effectors, the synthesis of cell cycle proteins such as cyclin D and hypoxia-inducible factor-1a (HIF-1a) are increased. HIF-1a then stimulates VEGF. Whether or not mTOR kinase is activated, determines whether the tumor cell produces key proteins needed for proliferation, growth, survival, and angiogenesis. mTOR is activated in tumor cells by various mechanisms including growth factor surface receptor tyrosine kinases, oncogenes, and loss of tumor suppressor genes. These activating factors are known to be important for malignant transformation and progression. mTOR is particularly important in the biology of renal cancer (RCC) owing to its function in regulating HIF-1a levels. Mutation or loss of the von Hippel Lindau tumor-suppressor gene is common in RCC and is manifested by reduced degradation of HIF-1a. In RCC tumors, activated mTOR further exacerbates accumulation of HIF-1a by increasing synthesis of this transcription factor and its angiogenic target gene products. Temsirolimus is a specific inhibitor of mTOR and interferes with the synthesis of proteins that regulate proliferation, growth, and survival of tumor cells. Treatment with temsirolimus leads to cell cycle arrest in the G1 phase, and also inhibits tumor angiogenesis by reducing synthesis of VEGF.
Biological target: | Temsirolimus is an inhibitor of mTOR with an IC50 of 1.76 μM. |
In vitro activity: | To determine the mechanism of CCI-779 (temsirolimus) inhibition in Bel-7402 cells, this study examined the activities of proteins in the mTOR signaling pathway by western blot. They were: mTOR and phospho-mTOR (Ser2448), downstream target p70S6K and p-p70S6K(Thr389), S6 and phospho-S6 (Ser240/244), 4EBP1 and p-4EBP1(Thr37/46). As shown in Figure 4, CCI-779 inhibited the phosphorylation of mTOR, p70S6K, S6 and 4EBP1, and slightly suppressed the expressions of mTOR, p70S6K, 4EBP1 and S6 in Bel-7402 cells. Reference: Cancer Cell Int. 2013; 13: 30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3632488/ |
In vivo activity: | Next, this study examined the total protein concentration in BALF (BAL fluid) and the amount of EBD (Evans blue dye) in lungs to assess the capillary-alveolar permeability in the lungs. As shown Fig. 1, B and C, the variables significantly increased in mice treated with temsirolimus in a dose-dependent manner. This study further investigated whether temsirolimus induced recruitment of inflammatory cells into the alveolar space. Diff-Quick staining of BAL cells revealed that the number of inflammatory cells, including neutrophils, lymphocytes, monocytes, and eosinophils, were elevated by temsirolimus in a dose-dependent manner. Increases in neutrophils and monocytes were predominantly detected at 2 wk of treatment, whereas lymphocytes in BALF were increased in a treatment duration-dependent manner (Fig. 1, D–F). Reference: Am J Physiol Lung Cell Mol Physiol. 2014 Jun 15;306(12):L1117-28. https://pubmed.ncbi.nlm.nih.gov/24793166/ |
Solvent | Max Conc. mg/mL | Max Conc. mM | |
---|---|---|---|
Solubility | |||
DMSO | 57.9 | 56.18 | |
DMF | 20.0 | 19.41 | |
DMF:PBS (pH 7.2) (1:4) | 0.2 | 0.19 | |
Ethanol | 71.0 | 68.92 |
The following data is based on the product molecular weight 1,030.29 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. Al Mamun Bhuyan A, Cao H, Lang F. Triggering of Eryptosis, the Suicidal Erythrocyte Death by Mammalian Target of Rapamycin (mTOR) inhibitor Temsirolimus. Cell Physiol Biochem. 2017;42(4):1575-1591. doi: 10.1159/000479398. Epub 2017 Jul 24. PMID: 28793293. 2. Li S, Liang Y, Wu M, Wang X, Fu H, Chen Y, Wang Z. The novel mTOR inhibitor CCI-779 (temsirolimus) induces antiproliferative effects through inhibition of mTOR in Bel-7402 liver cancer cells. Cancer Cell Int. 2013 Mar 28;13:30. doi: 10.1186/1475-2867-13-30. PMID: 23537100; PMCID: PMC3632488. 3. Chang HW, Wu MJ, Lin ZM, Wang CY, Cheng SY, Lin YK, Chow YH, Ch'ang HJ, Chang VHS. Therapeutic Effect of Repurposed Temsirolimus in Lung Adenocarcinoma Model. Front Pharmacol. 2018 Jul 24;9:778. doi: 10.3389/fphar.2018.00778. PMID: 30087612; PMCID: PMC6066584. 4. Washino S, Ando H, Ushijima K, Hosohata K, Kumazaki M, Mato N, Sugiyama Y, Kobayashi Y, Fujimura A, Morita T. Temsirolimus induces surfactant lipid accumulation and lung inflammation in mice. Am J Physiol Lung Cell Mol Physiol. 2014 Jun 15;306(12):L1117-28. doi: 10.1152/ajplung.00251.2013. Epub 2014 May 2. PMID: 24793166. |
In vitro protocol: | 1. Al Mamun Bhuyan A, Cao H, Lang F. Triggering of Eryptosis, the Suicidal Erythrocyte Death by Mammalian Target of Rapamycin (mTOR) inhibitor Temsirolimus. Cell Physiol Biochem. 2017;42(4):1575-1591. doi: 10.1159/000479398. Epub 2017 Jul 24. PMID: 28793293. 2. Li S, Liang Y, Wu M, Wang X, Fu H, Chen Y, Wang Z. The novel mTOR inhibitor CCI-779 (temsirolimus) induces antiproliferative effects through inhibition of mTOR in Bel-7402 liver cancer cells. Cancer Cell Int. 2013 Mar 28;13:30. doi: 10.1186/1475-2867-13-30. PMID: 23537100; PMCID: PMC3632488. |
In vivo protocol: | 1. Chang HW, Wu MJ, Lin ZM, Wang CY, Cheng SY, Lin YK, Chow YH, Ch'ang HJ, Chang VHS. Therapeutic Effect of Repurposed Temsirolimus in Lung Adenocarcinoma Model. Front Pharmacol. 2018 Jul 24;9:778. doi: 10.3389/fphar.2018.00778. PMID: 30087612; PMCID: PMC6066584. 2. Washino S, Ando H, Ushijima K, Hosohata K, Kumazaki M, Mato N, Sugiyama Y, Kobayashi Y, Fujimura A, Morita T. Temsirolimus induces surfactant lipid accumulation and lung inflammation in mice. Am J Physiol Lung Cell Mol Physiol. 2014 Jun 15;306(12):L1117-28. doi: 10.1152/ajplung.00251.2013. Epub 2014 May 2. PMID: 24793166. |
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