Successful, we will reply to you quickly.OK
Please select the quantity.OK
Your message is being sent, please wait.Close
Send mail failed, please send again!Close
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|
BMS 299897 is a sulfonamide <b>(gamma)-secretase</b> inhibitor with an <b>IC<sub>50</sub></b> of 7 nM for A(beta) production inhibition in HEK293 cells stably overexpressing amyloid precursor protein (APP).
Avagacestat (BMS-708163) is a potent, selective, orally bioavailable (gamma)-secretase inhibitor of A(beta)40 and A(beta)42 with IC50 of 0.3 nM and 0.27 nM, demonstrating a 193-fold selectivity against Notch.
CHF5074 is a novel (gamma)-secretase modulator, reduces A(beta)42 and A(beta)40 secretion, with an IC50 of 3.6 and 18.4 (mu)M, respectively.
DAPT(GSI-IX) is an inhibitor of (gamma)-secretase; DAPT causes a reduction in A(beta)40 and A(beta)42 levels in human primary neuronal cultures (IC50 values are 115 and 200 nM for total A(beta) and A(beta)42 respectively) and in brain extract, cerebrospinal fluid and plasma in vivo.
E 2012 is a potent (gamma)-secretase modulator.
(gamma)-secretase inhibitior-1 is a gamma-secretase modulator, (gamma)-secretase inhibitior-1 is useful for Alzheimer(acute)s disease.
gamma-secretase modulator 2 is a potent and selective (gamma)-secretase modulator for treatment of Alzheimer(acute)s disease.
gamma-secretase modulator 3 is a gamma-secretase modulator.
L-685458 is a potent inhibitor of Amyloid (beta)-Protein precursor (gamma)-secretase activity with IC50 of 17 nM, shows greater than 50-100-fold selectivity over other aspartyl proteases tested.
Semagacestat (LY450139) is a (gamma)-secretase blocker for A(beta)42, A(beta)40 and A(beta)38 with IC50 of 10.9 nM, 12.1 nM and 12.0 nM, also inhibits Notch signaling with IC50 of 14.1 nM.