847925-91-1

Basic information

• Product Name: RO4929097
• Synonyms: RO4929097;N1-[(7S)-6,7-Dihydro-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2,2-dimethyl-N3-(2,2,3,3,3-pentafluoropropyl)propanediamide;Propanediamide, N1-[(7S)-6,7-dihydro-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2,2-dimethyl-N3-(2,2,3,3,3-pentafluoropropyl)-;N1-[(7S)-6,7-Dihydro-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2,2-dimethyl-N3-(2,2,3,3,3-pentafluoropropyl)propanediamide Ro 4929097;Ro 4929097 N1-[(7S)-6,7-Dihydro-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2,2-dimethyl-N3-(2,2,3,3,3-pentafluoropropyl)propanediamide;RO4929097, >=98%;N1-[(7S)-6,7-Dihydro-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2,2-dimethyl-N3-(2,2,3,3,3-pentafluoropr;RO 4929097, 98%, a γ secretase inhibitor
• CAS NO: 847925-91-1
• Molecular Formula: C22H20F5N3O3
• Molecular Weight: 469.42
• EINECS: -0
• Product Categories: Inhibitors
• Mol File: 847925-91-1.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 696.312 °C at 760 mmHg
• Flash Point: 374.916 °C
• Appearance: /
• Density: 1.40
• Solubility: ≥23.47 mg/mL in DMSO; insoluble in H2O; ≥45.2 mg/mL in EtOH with ultrasonic
• PKA: 12.35±0.46(Predicted)
• CAS DataBase Reference: RO4929097(CAS DataBase Reference)
• NIST Chemistry Reference: RO4929097(847925-91-1)
• EPA Substance Registry System: RO4929097(847925-91-1)

Safety Data

• Hazardous Substances Data: 847925-91-1(Hazardous Substances Data)

Usage

Description

RO4929097, also known as a γ-secretase inhibitor, is a member of the class of dibenzoazepines that is formed from the amide condensation of a specific carboxy group with an amino group. It is a pharmaceutical compound with potential applications in cancer treatment.
Used in Oncology:
RO4929097 is used as an anticancer agent for the treatment of patients suffering from solid tumors, specifically targeting pancreatic adenocarcinoma. As a γ-secretase inhibitor, it plays a crucial role in modulating signaling pathways associated with tumor growth and progression, offering a therapeutic approach for cancer management.

Biological Activity

ro4929097 is a small-molecule inhibitor of γ secretase with ic50 of 4 nm and ec50 of 5 nm [1]. it shows no in vitro inhibitory activity on the closely related proteases. it also has greater than 100-fold selectivity with respect to 75 other proteins of various types [1]. ro4929097 binds to γ secretase and inhibits its protease activity, therefore blocking the cleavage of notch and reducing notch signaling. up-regulaton of this signaling pathway promotes tumorigenesis of multiple cancers.ro4929097 has shown potential antitumor activity both in vitro and in vivo. it impaired the growth of melanoma cell lines and tumor formation of human primary melanoma xenograft [2]. it slowed proliferation and reduces colony formation of breast cancer cell lines[1]. in addition, ro4929097 decreased tumor formation in xenograft models of colorectal, pancreatic, lung cancer and melanoma[1, 2]. ro4929097 has been tested in multiple phase i/ii

references

1. luistro l, he w, smith m et al. preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties. cancer res 2009; 69: 7672-7680. 2. huynh c, poliseno l, segura mf et al. the novel gamma secretase inhibitor ro4929097 reduces the tumor initiating potential of melanoma. plos one 2011; 6: e25264. 3. richter s, bedard pl, chen ex et al. a phase i study of the oral gamma secretase inhibitor r04929097 in combination with gemcitabine in patients with advanced solid tumors (phl-078/ctep 8575). invest new drugs 2014; 32: 243-249. 4. sahebjam s, bedard pl, castonguay v et al. a phase i study of the combination of ro4929097 and cediranib in patients with advanced solid tumours (pjc-004/nci 8503). br j cancer 2013; 109: 943-949. 5. diaz-padilla i, hirte h, oza am et al. a phase ib combination study of ro4929097, a gamma-secretase inhibitor, and temsirolimus in patients with advanced solid tumors. invest new drugs 2013; 31: 1182-1191. 6. tolcher aw, messersmith wa, mikulski sm et al. phase i study of ro4929097, a gamma secretase inhibitor of notch signaling, in patients with refractory metastatic or locally advanced solid tumors. j clin oncol 2012; 30: 2348-2353. 7. strosberg jr, yeatman t, weber j et al. a phase ii study of ro4929097 in metastatic colorectal cancer. eur j cancer 2012; 48: 997-1003. 8. kolb ea, gorlick r, keir st et al. initial testing (stage 1) by the pediatric preclinical testing program of ro4929097, a gamma-secretase inhibitor targeting notch signaling. pediatr blood cancer 2012; 58: 815-818.

Relevant articles and documents

Malonamide derivatives

The invention relates to malonamide derivatives of formula wherein each of the variables are as defined herein and to pharmaceutically acceptable acid addition salts, optically pure enantiomers, racemates and diastereomeric mixtures thereof. These compounds are γ-secretase inhibitors and may be used for the treatment of Alzheimer's disease.