Temsirolimus is a semisynthetic macrocyclic lactone prepared from Rapamycin. It is a dihydroxymethyl propionic acid ester and analog of Rapamycin. The compound is prepared by selective acylation of the 42-hydroxy group with a protected bis (dihydromethyl) propionic acid, followed by deprotection.
Temsirolimus is an antiproliferative and antiangiogenic mTOR inhibitor. mTOR protein has a role in integrating environmental signals that affect cell growth and proliferation. It has anti-neoplastic properties and immune-modulating activity. It can be used in kinase phosphatase biology research.
Temsirolimus is soluble in ethanol, methanol, DMF and DMSO.
| Mechanism of Action | Temsirolimus binds to receptor protein, FKBP12. The complex then binds to mTOR preventing it from interacting with target proteins. |
| Cancer Applications | Temsirolimus can be used in renal-cell carcinoma (RCC). The rationale for using mTOR inhibitors to treat malignancies has focused on the direct, growth-inhibitory effects.
It is surprising that Temsirolimus can enhance anti-tumor immunity. In an expimental murine model of RCC (RENCA), the combination of an HSP-based cancer vaccine and Temsirolimus was more effective against tumors than either agent alone. In animal models of tumor vaccines, Temsirolimus enhanced vaccine activity by enhancing effector T-cell function and enhancing production of CD8 memory T cells (Wang et al, 2011). Temsirolimus can induce antiproliferative effects by inhibiting mTOR in Bel-7402 liver cancer cells. Viability tests, and flow cytometry was used to analyze cell cycle after treatment. It can inhibit mTOR signaling and proliferation in vitro, for a promising strategy for liver cancer (Li et al, 2013). |
| References |
Li S, Liang Y and Wang Z (2013) The novel mTOR inhibitor CCI-779 (temsirolimus) induces antiproliferative effects through inhibition of mTOR in Bel-7402 liver cancer cells. Cancer Cell Int. 13:30 Wan X. et al (2006) CCI-779 inhibits rhabdomyosarcoma xenograft growth by an antiangiogenic mechanism linked to the targeting of mTOR/Hif-1α/VEGF signaling. Neoplasia 8:394 Wang Y, Wang X-Y, Subjeck JR, Shikrant PA and Kim HL (2011) Temsirolimus, an mTOR inhibitor, enhances anti-tumour effects of heat shock protein cancer vaccines. Transl. Ther. 104:643-652 |