RO4929097

• CAT Number: I005077
• CAS Number: 847925-91-1
• Molecular Formula: C₂₂H₂₀F₅N₃O₃
• Molecular Weight: 469.4
• Purity: ≥95%
• Target: Gamma Secretase
• Solubility: DMSO: ≥ 49 mg/mL
• Storage: 3 years -20C powder
• IC50: 4 nM
• InChI: InChI=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
• InChIKey: OJPLJFIFUQPSJR-INIZCTEOSA-N
• SMILES: CC(C)(C(=O)NCC(C(F)(F)F)(F)F)C(=O)NC1C2=CC=CC=C2C3=CC=CC=C3NC1=O

RO4929097 (Cat.No:I005077) is a small molecule gamma-secretase inhibitor used in preclinical studies for cancer research. It targets the gamma-secretase enzyme complex, which plays a role in the Notch signaling pathway. RO4929097 has shown promise in inhibiting tumor growth and stem cell-like properties in certain cancers, paving the way for potential therapeutic applications.

Reference

1:Phase I study of RO4929097 with bevacizumab in patients with recurrent malignant glioma. Pan E, Supko JG, Kaley TJ, Butowski NA, Cloughesy T, Jung J, Desideri S, Grossman S, Ye X, Park DM.J Neurooncol. 2016 Dec;130(3):571-579. Epub 2016 Nov 8. PMID: 27826680 2:Anti-myeloma effect of pharmacological inhibition of Notch/gamma-secretase with RO4929097 is mediated by modulation of tumor microenvironment. Pisklakova A, Grigson E, Ozerova M, Chen F, Sullivan DM, Nefedova Y.Cancer Biol Ther. 2016 May 3;17(5):477-85. doi: 10.1080/15384047.2016.1156261. Epub 2016 Mar 2. PMID: 26934342 Free PMC Article3:A phase II study of single-agent RO4929097, a gamma-secretase inhibitor of Notch signaling, in patients with recurrent platinum-resistant epithelial ovarian cancer: A study of the Princess Margaret, Chicago and California phase II consortia. Diaz-Padilla I, Wilson MK, Clarke BA, Hirte HW, Welch SA, Mackay HJ, Biagi JJ, Reedijk M, Weberpals JI, Fleming GF, Wang L, Liu G, Zhou C, Blattler C, Ivy SP, Oza AM.Gynecol Oncol. 2015 May;137(2):216-22. doi: 10.1016/j.ygyno.2015.03.005. Epub 2015 Mar 11. PMID: 25769658 4:Inhibition of the NOTCH pathway using γ-secretase inhibitor RO4929097 has limited antitumor activity in established glial tumors. Dantas-Barbosa C, Bergthold G, Daudigeos-Dubus E, Blockus H, Boylan JF, Ferreira C, Puget S, Abely M, Vassal G, Grill J, Geoerger B.Anticancer Drugs. 2015 Mar;26(3):272-83. doi: 10.1097/CAD.0000000000000190. PMID: 25486598 5:A multicenter phase 1 study of γ -secretase inhibitor RO4929097 in combination with capecitabine in refractory solid tumors. LoConte NK, Razak AR, Ivy P, Tevaarwerk A, Leverence R, Kolesar J, Siu L, Lubner SJ, Mulkerin DL, Schelman WR, Deming DA, Holen KD, Carmichael L, Eickhoff J, Liu G.Invest New Drugs. 2015 Feb;33(1):169-76. doi: 10.1007/s10637-014-0166-6. Epub 2014 Oct 17. PMID: 25318436 Free PMC Article6:Phase 2 study of RO4929097, a gamma-secretase inhibitor, in metastatic melanoma: SWOG 0933. Lee SM, Moon J, Redman BG, Chidiac T, Flaherty LE, Zha Y, Othus M, Ribas A, Sondak VK, Gajewski TF, Margolin KA.Cancer. 2015 Feb 1;121(3):432-40. doi: 10.1002/cncr.29055. Epub 2014 Sep 23. PMID: 25250858 Free PMC Article7:A phase II study of the gamma secretase inhibitor RO4929097 in patients with previously treated metastatic pancreatic adenocarcinoma. De Jesus-Acosta A, Laheru D, Maitra A, Arcaroli J, Rudek MA, Dasari A, Blatchford PJ, Quackenbush K, Messersmith W.Invest New Drugs. 2014 Aug;32(4):739-45. doi: 10.1007/s10637-014-0083-8. Epub 2014 Mar 27. PMID: 24668033 Free PMC Article8:A phase I study of the combination of ro4929097 and cediranib in patients with advanced solid tumours (PJC-004/NCI 8503). Sahebjam S, Bedard PL, Castonguay V, Chen Z, Reedijk M, Liu G, Cohen B, Zhang WJ, Clarke B, Zhang T, Kamel-Reid S, Chen H, Ivy SP, Razak AR, Oza AM, Chen EX, Hirte HW, McGarrity A, Wang L, Siu LL, Hotte SJ.Br J Cancer. 2013 Aug 20;109(4):943-9. doi: 10.1038/bjc.2013.380. Epub 2013 Jul 18. PMID: 23868004 Free PMC Article9:A phase Ib combination study of RO4929097, a gamma-secretase inhibitor, and temsirolimus in patients with advanced solid tumors. Diaz-Padilla I, Hirte H, Oza AM, Clarke BA, Cohen B, Reedjik M, Zhang T, Kamel-Reid S, Ivy SP, Hotte SJ, Razak AA, Chen EX, Brana I, Wizemann M, Wang L, Siu LL, Bedard PL.Invest New Drugs. 2013 Oct;31(5):1182-91. doi: 10.1007/s10637-013-0001-5. Epub 2013 Jul 17. PMID: 23860641 Free PMC Article10:PTEN regulates sensitivity of melanoma cells to RO4929097, the γ-secretase inhibitor. Nair JS, Sheikh T, Ho AL, Schwartz GK.Anticancer Res. 2013 Apr;33(4):1307-16. PMID: 23564767