WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 202510
Description: rosabulin ( STA-5312) is a novel microtubule inhibitor with a distinct binding site from other agents such as vincristine, colchicine, or paclitaxel, which has demonstrated antitumor activity against a range of solid tumors in chemotherapy-resistant cancer. Phase I study showed that STA-5312 appears to be well tolerated when given weekly in doses up to 32mg/m2. The MTD has not been determined and enrollment is ongoing. (source: asco.org)
MedKoo Cat#: 202510
Chemical Formula: C22H16N4O2S
Exact Mass: 400.0994
Molecular Weight: 400.45
Elemental Analysis: C, 65.98; H, 4.03; N, 13.99; O, 7.99; S, 8.01
IUPAC/Chemical Name: 3-[(4-Cyanophenyl)methyl]-N-(3-methyl-5-isothiazolyl)-alpha-oxo-1-indolizineacetamide
InChi Key: IZZYUABKZYIINT-UHFFFAOYSA-N
InChi Code: InChI=1S/C22H16N4O2S/c1-14-10-20(29-25-14)24-22(28)21(27)18-12-17(26-9-3-2-4-19(18)26)11-15-5-7-16(13-23)8-6-15/h2-10,12H,11H2,1H3,(H,24,28)
SMILES Code: O=C(NC1=CC(C)=NS1)C(C2=C3C=CC=CN3C(CC4=CC=C(C#N)C=C4)=C2)=O
STA-5312, 2-[3-(4-cyano-benzyl)-indolizin-1-yl]-N-(3-methyl-isothiazol-5-yl)-2-oxo-acetamide, is a new chemical entity being developed for the treatment of chemotherapy-resistant tumors. STA-5312 demonstrates substantial anti-proliferative activity against a wide range of cancer cell linesin vitro, with IC50 values extending down into the nanomolar range. The in vitro cytotoxic effects have been demonstrated across a wide array of tumor types, including hematologic and solid tumor cell lines of various origins (e.g. leukemia, lymphoma, breast, colon, uterine). Cell lines with multi-drug resistant (MDR) phenotypes were similarly sensitive to STA-5312. The mechanism of action for STA-5312 is inhibition of microtubule assembly and subsequent arrest of the cell cycle. STA-5312 is active against several tumor cell lines that express moderate to high levels of P-glycoprotein (Pgp), including lines insensitive to Taxol, Vincristine, and Adriamycin in which Pgp activity is a major contributor to the MDR phenotype. When dosed orally or intravenously, STA-5312 has shown in vivo activity in several murine tumors as well as human tumor xenograft models, including drug resistant tumors. Data on the murine leukemia P388 suggested activity in a vincristine-resistant cell line, and data in the RL human Lymphoma cell line suggested an additive effect of Taxol plus STA-5312. Thus, STA-5312 is a potential new therapy for the treatment of cancer including chemoresistant tumors. Considering the breadth of antitumor activity demonstrated by STA-5312 both in vitro and in vivo, two lines of clinical investigation are envisioned encompassing both hematologic and solid tumors. see: Synta Pharmaceuticals Corp's meeting abstract.
STA-5312 inhibits microtubule function, critical to cancer cell proliferation, through a unique binding site. Ongoing phase 1 studies of STA- 5312 in hematological and solid tumor malignancies are expected to be completed in the first half of 2006. The study findings will guide future clinical investment decisions for the compound.
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