Temsirolimus

Biological Activity

Temsirolimus is the active ingredient sold under the brand name of drug Torisel^®, which has been approved in some countries for the treatment of renal cell carcinoma (RCC). [Note: Temsirolimus sold by Gene Operation is for scientific research use only, not for human and veterinary use.]

Temsirolimus (CCI-779), a dihydroxymethyl propionic acid ester of rapamycin, is an effective inhibitor of mTOR developed for intravenous use in cancer chemotherapy. CCI-779 has displayed anticancer activity alone or in combination with cytotoxic agents in a variety of preclinical models such as glioblastoma, rhabdomyosarcoma, neuroectodermal tumour such as prostate, pancreatic and breast cancer cells ^[1-3] and is being evaluated in phase II clinical trials for some cancers ^[4-5]. In a panel of eight breast cancer lines, six of which are sensitive (IC₅₀ ≤50 nM) and two lines are resistant (IC₅₀>1.0 μM) to CCI-779. Sensitive lines are estrogen dependent (MCF-7, BT-474, T-47D), or lacked expression of the tumor suppressor PTEN (MDA-MB-468, BT-549), and/or overexpressed the Her-2/neu oncogene (SKBR-3, BT-474). Resistant lines (MDA-MB-435,MDA-MB-231) share none of these properties. CCI-779 (50 nM) suppresses mTOR function in both a sensitive and a resistant line ^[6]. In combination with MOR antagonist Methylnaltrexone (MNTX), CCI-779 enhances inhibition of VEGF-induced EC proliferation and migration with an IC₅₀shift from ~10 nM to ~1 nM and from ~50 to ~10 nM respectively ^[7]. A p70(s6) kinase assay in PBMCs is currently being incorporated in Phase I and II studies with CCI-779 to determine its relationship with dose and plasma concentration of the agent and its value as a predictor of treatment efficacy ^[8].

Chemical Properties

Cas No.: 162635-04-3	M. Wt.: 1030.29
Formula: C56H87NO16	Purity: >99%
Synonym: cell cycle inhibitor 779, CCI-779, Torisel®
Chemical Name: Rapamycin 42-[3-Hydroxy-2-(hydroxymethyl)-2-methylpropanoate
Appearance: White to off-white solid
Solubility: Soluble in DMSO (200 mg/ml) or Ethanol (200 mg/ml), very poorly soluble in water.
Storage: Store solid at -20 ºC for the stability of 2 years.