Choose Your Country or Region

TEMSIROLIMUS

by Selleckchem | Jun 11 2012

TEMSIROLIMUS: mTOR INHIBITOR
Protein kinase mTOR are the enzymes that come under the category of phosphatidylinositol 3-kinase or PI3-K that control the cell migration, cell multiplication, cell transcriptional and translational actions and cell survival. The fact that these inhibitors are involved in the above described processes, these enzymes have come into lime light for cancer therapy. In the recent years Temsirolimus mTOR inhibitor has got more popularity as compared to Rapamycin which was used in the late years.
For the cure of RCC or renal cell carcinoma Temsirolimus Torisel is among the rare inhibitors which is waiting for its approval by FDA. Temsirolimus 162635-04-3 is developed by a pharmaceutical company called Wyeth and it is administered to the patientsintravenously.CCI-779 is the other name of Temsirolimus. Researchers and scientists can purchase Temsirolimus for $100 as Temsirolimus price from suppliers in packaging of 200mg.Torisol is its trade name which is marketed by Temsirolimus supplier. Structural studies revealed that it mimics the structure of another drug called Sirolimus. Temsirolimus solubility is approximately 200mg/ml of ethanol or DMSO while it is completely insoluble in water. Storage at -20ºC gives Temsirolimus stability for 2 years. It is available in different costs depending upon the purity of salt.

TEMSIROLIMUS: THERAPEUTIC USES AND MODE OF ACTION
The mechanism of action of Temsirolimus CCI-779 is same as that of other various mTOR inhibitors [1]. Various types of cancers in past years and specifically recently Pompe disease are being treated by the administration of Temsirolimus. Actually to make susceptible to Cisplatin therapy the SCLC patients were treated with Temsirolimus [4]. The complete assessment and strong indications was done to study its anti-angiogenic characteristics in both in-vivo and in-vitro and it showed promising results.
As angiogenic medicine it has shown fruitful results in models of xenograft of rhabdomyosarcoma [6]. In PyMT or preclinical mammary tumor models Temsirolimus showed good efficiency against it [8] also it has been co-administered with different drugs to treat breast cancer [7]. The safety of Temsirolimus was evaluated in patients of metastasized cancer [9] and those suffering from advanced RCC [10]. These studies supported to use Interferonwith Temsirolimus in phase I and II clinical trials [12].

TEMSIROLIMUS: CLINICAL TRIALS
In phase I clinical trials for the therapy of advanced types of tumor Temsirolimus was administered as combinatorial therapy [14] when pharmacokinetics characteristics of Temsirolimus were evaluated in phase I [13]. For breast cancer and gynecological cancer treatment Temsirolimus was co-administered in phase I and it was found that it has more efficiency against breast carcinoma when administered alone in phase II trials [16]. In phase-I Temsirolimus has showed promising results against solid types of tumors [17] when administered alone or with other medicines [18]. Temsirolimus has also been approved for therapy of pediatric cancer patients [19]. Clinical levels of phase II showed excellent results against NSCLC when administered with Temsirolimus [20].
Results obtained against mantle cell lymphoma were most outstanding among Temsirolimus clinical trials. In this Temsirolimus was administered in very minute dosage in those trials [21] of phase II or co-administered with other drugs [22]. The outstanding results shown by Temsirolimus in those trials forced scientist to use Temsirolimus for the treatment of mantle cell lymphoma in clinical trials phase III and it showed promising results as expected [23]. Excellent results were shown in clinical levels of phase II conducted against ovarian [24], endometrium [25], soft tissue [26], neuroendocrine [27] and most significantly glioblastoma cancer [28].

REFERENCES:
1. Rini, B.I.e.a., Temsirolimus, an Inhibitor of Mammalian Target of Rapamycin. Clin Cancer Res, 2008.
2. Dancey, J.E.e.a., Evaluating Temsirolimus Activity in Multiple Tumors: A Review of Clinical Trials. Seminars in Oncology, 2009.
3. Ashe, K.M.e.a., Inhibition of glycogen biosynthesis via mTORC1 suppression as an adjunct therapy for Pompe disease. Molecular Genetics and Metabolism, 2010.
4. Wu, C.e.a., Overcoming cisplatin resistance by mTOR inhibitor in lung cancer. Mol. Cancer, 2005.
5. Del Bufalo, D.e.a., Antiangiogenic potential of the Mammalian target of rapamycin inhibitor temsirolimus. Cancer Res., 2006.
6. Wan, X.e.a., CCI-779 inhibits rhabdomyosarcomaxenograft growth by an antiangiogenic mechanism linked to the targeting of mTOR/Hif-1alpha/VEGF signaling. Neoplasia, 2006.
7. Sadler, T.M.e.a., Combination therapy for treating breast cancer using antiestrogen, ERA-923, and the mammalian target of rapamycin inhibitor, temsirolimus. EndocrRelat Cancer, 2006
8. Wang, X.e.a., Multi-Modal Biomarker Investigation on Efficacy and Mechanism of Action for the mTOR inhibitor, Temsirolimus, in a Preclinical Mammary Carcinoma Oncomouse (PyMT) Model: A Translational Medicine Study in Support for Early Clinical Development. Journal of Pharmacology and Experimental Therapeutics, 2011.
9. Lamm, W.e.a., Safety and efficacy of temsirolimus in heavily pretreated patients with metastatic renal cell carcinoma. ActaOncologica, 2011.
10. Bellmunt, J.e.a., Temsirolimus safety profile and management of toxic effects in patients with advanced renal cell carcinoma and poor prognostic features. Ann Oncol., 2008.
11. Grundbichler, M.e.a., Efficacy of Temsirolimus after Previous Treatment with Sunitinib, Sorafenib or Everolimus in Advanced Renal Cell Cancer. Oncology, 2011.
12. Motzer, R.J.e.a., Phase I/II Trial of Temsirolimus Combined With Interferon Alfa for Advanced Renal Cell Carcinoma. Journal of Clinical Oncology, 2007.
13. Hidalgo, M.e.a., A Phase I and Pharmacokinetic Study of Temsirolimus (CCI-779) Administered Intravenously Daily for 5 Days Every 2 Weeks to Patients with Advanced Cancer. Clin Cancer Res, 2006.
14. Naing, A.e.a., Phase I Trial of Cixutumumab Combined with Temsirolimus in Patients with Advanced Cancer. Clinical Cancer Research, 2011.
15. Moroney, J.W., A Phase I Trial of Liposomal Doxorubicin, Bevacizumab and Temsirolimus in Patients with Advanced Gynecologic and Breast Malignancies. Clinical Cancer Research, 2011.
16. Chan, S.e.a., Phase II Study of Temsirolimus (CCI-779), a Novel Inhibitor of mTOR, in Heavily Pretreated Patients With Locally Advanced or Metastatic Breast Cancer. Journal of Clinical Oncology, 2005.
17. MacKenzie, M.J.e.a., A phase I study of temsirolimus and metformin in advanced solid tumours. Investigational New Drugs, 2010.
18. Kollmannsberger, C.e.a., Temsirolimus in combination with carboplatin and paclitaxel in patients with advanced solid tumors: a NCIC-CTG, phase I, open-label dose-escalation study (IND 179). Ann Oncol., 2011.
19. Spunt, S.L.e.a., Phase I Study of Temsirolimus in Pediatric Patients With Recurrent/Refractory Solid Tumors. Journal of Clinical Oncology, 2011.
20. Pandya, K.e.a., A Randomized, Phase II Trial of Two Dose Levels of Temsirolimus (CCI-779) in Patients with Extensive-Stage Small-Cell Lung Cancer Who Have Responding or Stable Disease after Induction Chemotherapy: A Trial of the Eastern Cooperative Oncology Group (E1500). Journal of Thoracic Oncology, 2007.
21. Ansell, S.M.e.a., Low-dose, single-agent temsirolimus for relapsed mantle cell lymphoma. Cancer, 2008.
22. Ansell, S.M.e.a., Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study. The Lancet Oncology, 2011.
23. Hess, G.e.a., Phase III Study to Evaluate Temsirolimus Compared With Investigator's Choice Therapy for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma. Journal of Clinical Oncology, 2009.
24. Behbakht, K.e.a., Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: A Gynecologic Oncology Group study. Gynecologic Oncology, 2011.
25. Oza, A.M.e.a., Phase II Study of Temsirolimus in Women With Recurrent or Metastatic Endometrial Cancer: A Trial of the NCIC Clinical Trials Group. Journal of Clinical Oncology, 2011.
26. Okuno, S.e.a., A phase 2 study of temsirolimus (CCI-779) in patients with soft tissue sarcomas. Cancer, 2011.
27. Duran, I.e.a., A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas. British Journal of Cancer, 2006.
28. Galanis, E.e.a., Phase II Trial of Temsirolimus (CCI-779) in Recurrent GlioblastomaMultiforme: A North Central Cancer Treatment Group Study. Journal of Clinical Oncology, 2005.