RO4929097
RO4929097 (CAS 847925-91-1) is a potent, selective small-molecule inhibitor of γ-secretase, an essential protease in the Notch signaling pathway. It inhibits γ-secretase with high specificity (IC50: 4 nM; EC50: 5 nM), showing minimal inhibitory activity against closely related proteases and over 100-fold selectivity versus a broad spectrum of other proteases. By preventing Notch receptor cleavage and subsequent signaling activation, RO4929097 suppresses proliferation and tumorigenesis across various tumor models, including melanoma, breast, colorectal, pancreatic, and lung cancers. Clinical studies have assessed RO4929097 alone or combined with other anticancer agents for advanced solid tumors.
- 1. Sumin Sun, Sheng Huan, et al. "Curcumol alleviates liver fibrosis by inducing endoplasmic reticulum stress-mediated necroptosis of hepatic stellate cells through Sirt1/NICD pathway." PeerJ. 2022 May 12;10:e13376. PMID: 35582617
- 2. Jingman Li, Yuchen Pan, et al. "Urokinase-type plasminogen activator receptor is required for impairing toll-like receptor 7 signaling on macrophage efferocytosis in lupus." Mol Immunol. 2020 Nov;127:38-45. PMID: 32911323
- 3. Pont MJ, Hill T, et al. "γ-secretase inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma." Blood. 2019 Sep 26. pii: blood.2019000050. PMID: 31558469
- 4. Frank SB, Berger PL, et al. "Human prostate luminal cell differentiation requires NOTCH3 induction by p38-MAPK and MYC." J Cell Sci. 2017 Jun 1;130(11):1952-1964. PMID: 28446540
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 469.4 |
| Cas No. | 847925-91-1 |
| Formula | C22H20F5N3O3 |
| Solubility | ≥23.47 mg/mL in DMSO; insoluble in H2O; ≥45.2 mg/mL in EtOH with ultrasonic |
| Chemical Name | 2,2-dimethyl-N-[(7S)-6-oxo-5,7-dihydrobenzo[d][1]benzazepin-7-yl]-N'-(2,2,3,3,3-pentafluoropropyl)propanediamide |
| SDF | Download SDF |
| Canonical SMILES | CC(C)(C(=O)NCC(C(F)(F)F)(F)F)C(=O)NC1C2=CC=CC=C2C3=CC=CC=C3NC1=O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
SUM190 and SUM149 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
1 μM, 14 days for 2D cultures 7 days for 3D cultures |
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Applications |
After treating with increasing doses of ionizing radiation in the presence or absence of the drug, 2D colonies were allowed to grow for 10–14 days, while the mammospheres were permitted to grow for 1 week. At 1 μM, RO4929097 was able to sensitize adherent cells to radiation with a more significant effect seen in SUM190 than in SUM149 cells. However, the same dose of inhibitor radioprotected cells grown under conditions that favor the enrichment of the cancer stem cells at higher doses of ionizing radiation. This discrepancy between 2D and 3D cultures suggested that cell contact may be needed for a Notch inhibitor to have a significant effect. |
| Animal experiment: [2] | |
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Animal models |
NOD/SCID/IL2gammaR-/- (NOG) mice injected with WM3248 cells |
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Dosage form |
Oral administration, 10 mg/Kg/day for 30 days |
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Applications |
There was a decrease in tumor growth with RO4929097 treatment, which was more appreciable after tumors were extracted for weight assessment. RO4929097-treated tumors also displayed lower expression of putative melanoma stem cell markers CD166, CD271 and JARID1B compared to vehicle-treated ones. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Debeb B G, Cohen E N, Boley K, et al. Pre-clinical studies of Notch signaling inhibitor RO4929097 in inflammatory breast cancer cells. Breast cancer research and treatment, 2012, 134(2): 495-510. [2] Huynh C, Poliseno L, Segura M F, et al. The novel gamma secretase inhibitor RO4929097 reduces the tumor initiating potential of melanoma. PloS one, 2011, 6(9): e25264. |
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| Description | RO4929097 is an inhibitor of γ secretase with IC50 of 4 nM, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively. | |||||
| Targets | γ secretase | Aβ40 | ICN | |||
| IC50 | 4 nM | 14 nM | 5 nM | |||
Quality Control & MSDS
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Chemical structure
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