Temsirolimus | Torisel | CCI-779 | CAS#162635-04-3 | mTOR inhibitor |MedKoo Biosciences

MedKoo Cat#: 202870 | Name: Temsirolimus

Description:

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

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.

Chemical Structure

Temsirolimus

CAS#162635-04-3

Theoretical Analysis

MedKoo Cat#: 202870

Name: Temsirolimus

CAS#: 162635-04-3

Chemical Formula: C56H87NO16

Exact Mass: 1029.6025

Molecular Weight: 1030.29

Elemental Analysis: C, 65.28; H, 8.51; N, 1.36; O, 24.85

Price and Availability

Size	Price	Availability
10mg	USD 120.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship

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Related CAS #

No Data

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.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#T8Z04C18

QC Data

View QC data: current batch, Lot#T8Z04C18

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	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

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 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:

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.

1: Pinto-Fraga J, García-Chico C, Lista S, Lacal PM, Carpenzano G, Salvati M, Santos-Lozano A, Graziani G, Ceci C. protein kinase inhibitors as Targeted therapy for glioblastoma: A meta-analysis of randomized controlled clinical trials. Pharmacol Res. 2024 Dec 3:107528. doi: 10.1016/j.phrs.2024.107528. Epub ahead of print. PMID: 39637954. 2: Ara B, Babar A, Atif D, Ghafoor B, Shah M, Abdullah SM, Safi D, Kamran A. Systemic therapy for non-clear cell renal cell carcinomas: A systematic review. J Oncol Pharm Pract. 2024 Nov 11:10781552241289920. doi: 10.1177/10781552241289920. Epub ahead of print. PMID: 39529367. 3: Wang L, Cai F, Li Y, Lin X, Wang Y, Liang W, Liu C, Wang C, Ruan J. pH- Responsive Block Copolymer Micelles of Temsirolimus: Preparation, Characterization and Antitumor Activity Evaluation. Int J Nanomedicine. 2024 Sep 23;19:9821-9841. doi: 10.2147/IJN.S469913. PMID: 39345910; PMCID: PMC11430863. 4: Cui C, Zhu L, Han G, Sun J, Zhang L, Guo Y, Jiang P. Bioinformatics analysis of the mechanisms of traumatic brain injury-associated dementia based on the competing endogenous RNA. Psychopharmacology (Berl). 2024 Dec;241(12):2441-2452. doi: 10.1007/s00213-024-06691-w. Epub 2024 Sep 25. PMID: 39317770. 5: Tian RL, Wang TX, Huang ZX, Yang Z, Guan KL, Xiong Y, Wang P, Ye D. Temsirolimus inhibits FSP1 enzyme activity to induce ferroptosis and restrain liver cancer progression. J Mol Cell Biol. 2024 Sep 23:mjae036. doi: 10.1093/jmcb/mjae036. Epub ahead of print. PMID: 39313331. 6: Xin M, Peng H, Zhang L. Exploring the prognosis value, immune correlation, and drug responsiveness prediction of homeobox C6 (HOXC6) in lung adenocarcinoma. Discov Oncol. 2024 Aug 31;15(1):393. doi: 10.1007/s12672-024-01273-w. PMID: 39215852; PMCID: PMC11365874. 7: Stanciu SM, Jinga M, Miricescu D, Stefani C, Nica RI, Stanescu-Spinu II, Vacaroiu IA, Greabu M, Nica S. mTOR Dysregulation, Insulin Resistance, and Hypertension. 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IJU Case Rep. 2024 Apr 8;7(4):293-296. doi: 10.1002/iju5.12727. PMID: 38966764; PMCID: PMC11221937. 14: Elshazly AM, Elzahed AA, Gewirtz DA. The Cytoprotective and Cytotoxic Functions of Autophagy in Response to mTOR Inhibitors. Front Biosci (Landmark Ed). 2024 Jun 24;29(6):231. doi: 10.31083/j.fbl2906231. PMID: 38940039. 15: Gupta AA, Xue W, Harrison DJ, Hawkins DS, Dasgupta R, Wolden S, Shulkin B, Qumseya A, Routh JC, MacDonald T, Feinberg S, Crompton B, Rudzinski ER, Arnold M, Venkatramani R. Addition of temsirolimus to chemotherapy in children, adolescents, and young adults with intermediate-risk rhabdomyosarcoma (ARST1431): a randomised, open-label, phase 3 trial from the Children's Oncology Group. Lancet Oncol. 2024 Jul;25(7):912-921. doi: 10.1016/S1470-2045(24)00255-9. PMID: 38936378; PMCID: PMC11550893. 16: Hossain MA. Targeting the RAS upstream and downstream signaling pathway for cancer treatment. Eur J Pharmacol. 2024 Sep 15;979:176727. doi: 10.1016/j.ejphar.2024.176727. 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Epub 2024 May 20. PMID: 38767353; PMCID: PMC11324022. 20: Wang Z, Zheng Z, Wang B, Zhan C, Yuan X, Lin X, Xin Q, Zhong Z, Qiu X. Characterization of a G2M checkpoint-related gene model and subtypes associated with immunotherapy response for clear cell renal cell carcinoma. Heliyon. 2024 Apr 5;10(7):e29289. doi: 10.1016/j.heliyon.2024.e29289. PMID: 38617927; PMCID: PMC11015143.