Temsirolimus

Cas No.:	162635-04-3
Chemical Name:	CCI-779, NSC 683864
Synonyms:	CCI-779, NSC 683864
SMILES:	C[C@@H]1CC[C@H]2C[C@@H](/C(=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]([C@@H](/C(=C/[C@H](C(=O)C[C@H](OC(=O)[C@@H]3CCCCN3C(=O)C(=O)[C@@]1(O2)O)[C@H](C)C[C@@H]4CC[C@H]([C@@H](C4)OC)OC(=O)C(C)(CO)CO)C)/C)O)OC)C)C)/C)OC
Formula:	C56H87NO16
M.Wt:	1030.29
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Temsirolimus is an inhibitor of mTOR with an IC50 of 1.76 μM.
In Vivo:	CCI-779 (20 mg/kg, i.p.) inhibits the growth of both prostate cancer xenografts, and the rowth of PC-3 tumors is inhibited in a dose-dependent manner and growth inhibition is greater than for DU145 tumors[2]. In the NOD/SCID xenograft models with human ALL, Temsirolimus treatment at 10 mg/kg/day produces a decrease in peripheral blood blasts and in splenomegaly[3]. Administration of Temsirolimus (20 mg/kg, i.p. 5 days/week) significantly delays the growth of DAOY xenografts by 160% after 1 week and 240% after 2 weeks, compared with controls. Single high-dose of Temsirolimus (100 mg/kg, i.p) treatment induces 37% regression of tumor volume within 1 week. Temsirolimus treatment for 2 weeks also delays the growth of rapamycin-resistant U251 xenografts by 148%[4]. Inhibition of mTOR by Temsirolimus improves performance on four different behavioral tasks and decreases aggregate formation in a mouse model of Huntington disease[5]. Administration of Temsirolimus induces significant dose-dependent, antitumor responses against subcutaneous growth of 8226, OPM-2, and U266 xenografts with ED50 of 20 mg/kg and 2 mg/kg for 8226 and OPM-2, respectively, which are associated with inhibited proliferation and angiogenesis, induction of apoptosis, and reduction in tumor cell size[6].
In Vitro:	Temsirolimus potently inhibits mTOR kinase activity with IC50 of 1.76 μM, similar to that of rapamycin with IC50 of 1.74 μM in the absence of FKBP12. Temsirolimus (10 nM to <5 μM) displays a modest and selective antiproliferative activity via FKBP12-dependent mechanism, but can completely inhibit the proliferation of a broad panel of tumor cells at low micromolar concentrations (5-15 μM), involving FKBP12-independent suppression of mTOR signaling. Temsirolimus treatment at micromolar but not nanomolar concentrations (20 μM) causes a marked decline in global protein synthesis and disassembly of polyribosomes, accompanied by rapid increase in the phosphorylation of translation elongation factor eEF2 and the translation initiation factor eIF2A[1]. Temsirolimus inhibits the phosphorylation of ribosomal protein S6, more potently in PTEN-positive DU145 cells than in PTEN-negative PC-3 cells, and inhibits cell growth and clonogenic survival of both cells in a concentration-dependent manner[2]. Temsirolimus (100 ng/mL) potently inhibits proliferation and induces apoptosis in primary human lymphoblastic leukemia (ALL) cells[3].