RO4929097
{{Short description|Chemical compound}}
{{Infobox drug
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| IUPAC_name = 2,2-Dimethyl-N-[(10S)-9-oxo-8-azatricyclo[9.4.0.02,7]pentadeca-1(15),2,4,6,11,13-hexaen-10-yl]-N-(2,2,3,3,3-pentafluoropropyl)propanediamide
| image = RO4929097.svg
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| CAS_number = 847925-91-1
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = KK8645V7LE
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| PubChem = 49867930
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| ChemSpiderID = 25027400
| C=22|H=20|F=5|N=3|O=3
| smiles = O=C1Nc2ccccc2c2c(C1NC(=O)C(C(=O)NCC(C(F)(F)F)(F)F)(C)C)cccc2
| StdInChI = 1S/C22H20F5N3O3/c1-20(2,18(32)28-11-21(23,24)22(25,26)27)19(33)30-16-14-9-4-3-7-12(14)13-8-5-6-10-15(13)29-17(16)31/h3-10,16H,11H2,1-2H3,(H,28,32)(H,29,31)(H,30,33)/t16-/m0/s1
| StdInChIKey = OJPLJFIFUQPSJR-INIZCTEOSA-N
}}
RO4929097 (RG-4733) is a gamma secretase inhibitor being studied as an anti-cancer drug.{{cite journal | vauthors = Luistro L, He W, Smith M, Packman K, Vilenchik M, Carvajal D, Roberts J, Cai J, Berkofsky-Fessler W, Hilton H, Linn M, Flohr A, Jakob-Røtne R, Jacobsen H, Glenn K, Heimbrook D, Boylan JF | title = Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties | journal = Cancer Research | volume = 69 | issue = 19 | pages = 7672–80 | date = October 2009 | pmid = 19773430 | doi = 10.1158/0008-5472.CAN-09-1843 | pmc = 5260798 }} Targeting gamma secretase inhibits NOTCH signaling, which is upregulated in many forms of cancer.{{cite web | title = Gamma-secretase/Notch signalling pathway inhibitor RO4929097 |url=https://www.cancer.gov/publications/dictionaries/cancer-drug/def/gamma-secretase-inhibitor-ro4929097|work = NCI Drug Dictionary | publisher = National Cancer Institute}} The drug was initially developed by Roche for the treatment of Alzheimer's disease, but current research focuses on cancer.{{cite web|url=http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7338|title=RO4929097 | work = IUPHAR/BPS Guide to PHARMACOLOGY }} Production was halted in 2010, but began again in 2014.{{cite web | title = RG 4733 | url = https://adisinsight.springer.com/drugs/800027906 | work = AdisInsight | publisher = Springer Nature Switzerland AG}}
Research
Over 35 phase I and II clinical trials have been performed, but no phase III trials have yet commenced.{{cite web|url=https://clinicaltrials.gov/ct2/results?term=RO4929097|title=Search for: RO4929097 - List Results - ClinicalTrials.gov|publisher=}}
Phase II studies have investigated the use of RO4929097 in ovarian cancer,{{ClinicalTrialsGov|NCT01175343|RO4929097 in Treating Patients With Recurrent and/or Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer}} renal cell carcinoma in patients that were unsuccessful on anti-VEGF treatments,{{ClinicalTrialsGov|NCT01141569|A Study of RO4929097 in Patients With Advanced Renal Cell Carcinoma That Have Failed Vascular Endothelial Growth Factor (VEGF)/Vascular Endothelial Growth Factor Receptor (VEGFR) Therapy}} metastatic pancreatic cancer,{{ClinicalTrialsGov|NCT01232829|Gamma Secretase Inhibitor RO4929097 in Previously Treated Metastatic Pancreas Cancer}} advanced brain tumors,{{ClinicalTrialsGov|NCT01122901|Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Recurrent or Progressive Glioblastoma}} and relapsed non-small cell lung cancer.{{ClinicalTrialsGov|NCT01070927|An Exploratory Study of RO4929097 in Patients With Recurrent or Refractory Non-Small Cell Lung Cancer}}
Other planned clinical trials were terminated, because the drug became unavailable.{{ClinicalTrialsGov|NCT01216787|RO4929097 in Treating Patients With Stage IIIB, Stage IIIC, or Stage IV Melanoma That Can Be Removed by Surgery}}
References
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