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Products are for research use only. Not for human use. We do not sell to patients.
(RO-4929097; RO 4929097)
RO4929097 Chemical Structure
|Product name: RO4929097|
|Cat. No.: HY-11102|
RO4929097 is a γ secretase inhibitor with IC50 of 4 nM, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively.
IC50 value: 4 nM
Target: γ secretase
in vitro: RO4929097 decreases the amount of Aβ peptides secreted into the culture medium in HEK293 cells with EC50 of 14 nM. RO4929097 strongly inhibits Notch processing with EC50 of 5 nM in the Notch cell-based reporter assay. The potency of RO4929097 in cell-free and cellular assays is in the low nanomolar range with >100-fold selectivity observed with respect to 75 other proteins of various types including receptors, ion channels, and enzymes (CEREP panel). After 5 days of treatment, RO4929097 reduces the production of ICN in the human NSCLC A549 cells inducing a flattened and less transformed tumor cell phenotype in tissue culture . RO4929097 blocks Notch processing in human non-small cell lung carcinoma cells and decreases expression of the Notch transcriptional target gene Hes1. Treatment with RO4929097 reveals a two- to threefold decrease in the expression of direct Notch target genes, Hes1, Hey1, and Heyl in SUM149 and a 3.5- to eightfold decrease in expression in SUM190 cells. RO4929097 modestly inhibits the growth of SUM149 cells in a dose-dependent manner. At a concentration of 1 μM of RO4929097, growth inhibition is 20 % for SUM149 and 10 % for SUM190 cells, relative to vehicle-treated controls. RO4929097 decreases the production of inflammatory cytokines by T-cells. Furthermore, with RO4929097 treatment, there is a shift in favor of TH2 over TH1 cytokines. In addition, T-cell activation induced IL-6 production would be increased with RO4929097 . Upon RO4929097 treatment, the selected melanoma cell lines reveals downregulation of NOTCH downstream effector HES1. A decrease in the amount of melanospheres formed upon RO4929097 treatment in primary melanoma cell lines is detected .
in vivo: Oral injection of 3 to 60 mg/kg RO4929097 once daily or twice daily to nude mice bearing A549 NSCLC xenografts for either 7, 14, or 21 days of a 21-day schedule results in significant tumor growth inhibition compared with vehicle-treated animals. The tumor growth inhibition values ranges from 66% to 91%. When mice are treated with 60 mg/kg RO4929097 twice daily with the 7+/14- schedule, treatment initially arouses regression of established A549 tumors. At the end of the 21-day cycle (day 47), tumor growth prevention is still 91% compared with vehicle control mice. Inhibition of tumor growth remains prolonged and sustained up to 34 days post-treatment (day 67). On day 67, these mice are retreated with the same dose of RO4929097 for a second cycle (7 days) until day 74. Importantly, the antitumor effects are sustained after dosing is completed . RO4929097 leads to reduced expression of genes associated with angiogenesis in A549 xenograft model. In contrast, the RO4929097-resistant H460a xenograft displays little change in expression of these genes, underscoring the in vivo anti-angiogenesis mechanism of action of RO4929097 .
|M.Wt||469.4||Storage||Please store the product under the recommended conditions in the Certificate of Analysis.|
|Solvent & Solubility||
DMSO: ≥ 49 mg/mL
|1 mg||5 mg||10 mg|
|1 mM||2.1304 mL||10.6519 mL||21.3038 mL|
|5 mM||0.4261 mL||2.1304 mL||4.2608 mL|
|10 mM||0.2130 mL||1.0652 mL||2.1304 mL|
|Product Name||Sponsor Only||Condition||Start Date||End Date||Phase||Last Change Date|
|RO4929097||National Cancer Institute||Metastatic colorectal cancer||31-DEC-10||Phase 2||22-OCT-13|
|National Cancer Institute; The Cancer Institute of New Jersey||Prostate tumor||31-AUG-10||31-AUG-12||Phase 2||07-MAY-13|
|National Cancer Institute||Stage III melanoma||30-SEP-10||Phase 2||04-FEB-13|
|University of Colorado at Denver and Health Sciences Center||Pancreas tumor||31-OCT-10||Phase 2||06-SEP-13|
|National Cancer Institute||Multiple myeloma||31-DEC-10||31-JUL-12||Phase 2||29-OCT-13|
|National Cancer Institute||Stage IV melanoma||30-SEP-10||Phase 2||04-FEB-13|
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