WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 202412
CAS#: 847925-91-1
Description: RO4929097, also known as RO04929097, is an orally bioavailable, small-molecule gamma secretase (GS) inhibitor with potential antitumor activity. Gamma secretase inhibitor RO4929097 binds to GS and blocks activation of Notch receptors, which may inhibit tumor cell proliferation. The integral membrane protein GS is a multi-subunit protease complex that cleaves single-pass transmembrane proteins, such as Notch receptors, at residues within their transmembrane domains. Overexpression of the Notch signaling pathway has been correlated with increased tumor cell growth.
MedKoo Cat#: 202412
Name: RO4929097
CAS#: 847925-91-1
Chemical Formula: C22H20F5N3O3
Exact Mass: 469.14248
Molecular Weight: 469.40452
Elemental Analysis: C, 56.29; H, 4.29; F, 20.24; N, 8.95; O, 10.23
Synonym: R4733; R 4733; R-4733; RO4929097; RO-4929097; RO 4929097; RO04929097; RO-04929097; RO 04929097.
IUPAC/Chemical Name: (S)-2,2-dimethyl-N1-(6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl)-N3-(2,2,3,3,3-pentafluoropropyl)malonamide
InChi Key: OJPLJFIFUQPSJR-INIZCTEOSA-N
InChi Code: 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
SMILES Code: O=C(N[C@H]1C2=CC=CC=C2C3=CC=CC=C3NC1=O)C(C)(C)C(NCC(F)(F)C(F)(F)F)=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not soluble in water.
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 469.40452 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
1: Huynh C, Poliseno L, Segura MF, Medicherla R, Haimovic A, Menendez S, Shang S, Pavlick A, Shao Y, Darvishian F, Boylan JF, Osman I, Hernando E. Correction: The Novel Gamma Secretase Inhibitor RO4929097 Reduces the Tumor Initiating Potential of Melanoma. PLoS One. 2011;6(11). doi: 10.1371/annotation/a89c089f-ae9d-4453-a314-37efd5efb126. Epub 2011 Nov 2. PubMed PMID: 22073133; PubMed Central PMCID: PMC3207494.
2: Kolb EA, Gorlick R, Keir ST, Maris JM, Lock R, Carol H, Kurmasheva RT, Reynolds CP, Kang MH, Wu J, Houghton PJ, Smith MA. Initial testing (stage 1) by the pediatric preclinical testing program of RO4929097, a γ-secretase inhibitor targeting notch signaling. Pediatr Blood Cancer. 2011 Aug 16. doi: 10.1002/pbc.23290. [Epub ahead of print] PubMed PMID: 22052798.
3: Huynh C, Poliseno L, Segura MF, Medicherla R, Haimovic A, Menendez S, Shang S, Pavlick A, Shao Y, Darvishian F, Boylan JF, Osman I, Hernando E. The novel gamma secretase inhibitor RO4929097 reduces the tumor initiating potential of melanoma. PLoS One. 2011;6(9):e25264. Epub 2011 Sep 29. PubMed PMID: 21980408; PubMed Central PMCID: PMC3182998.
4: Wu J, Wiegand R, LoRusso P, Li J. Validation and implementation of a liquid chromatography/tandem mass spectrometry assay for quantitation of the total and unbound RO4929097, a γ-secretase inhibitor targeting Notch signaling, in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Jun 1;879(19):1537-43. Epub 2011 Mar 31. PubMed PMID: 21497565.
5: He W, Luistro L, Carvajal D, Smith M, Nevins T, Yin X, Cai J, Higgins B, Kolinsky K, Rizzo C, Packman K, Heimbrook D, Boylan JF. High tumor levels of IL6 and IL8 abrogate preclinical efficacy of the γ-secretase inhibitor, RO4929097. Mol Oncol. 2011 Jun;5(3):292-301. Epub 2011 Jan 21. PubMed PMID: 21315665.
6: 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. Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties. Cancer Res. 2009 Oct 1;69(19):7672-80. Epub 2009 Sep 22. PubMed PMID: 19773430.
RO4929097 decreased the levels of NOTCH transcriptional target HES1. This was accompanied by reduced proliferation and impaired ability to form colonies in soft agar and to organize in tridimensional spheres. Moreover, RO4929097 affected the growth of human primary melanoma xenograft in NOD/SCID/IL2gammaR-/- mice and inhibited subsequent tumor formation in a serial xenotransplantation model, suggesting that inhibition of NOTCH signaling suppresses the tumor initiating potential of melanoma cells. In addition, RO4929097 decreased tumor volume and blocked the invasive growth pattern of metastatic melanoma cell lines in vivo. Finally, increased gene expression of NOTCH signaling components correlated with shorter post recurrence survival in metastatic melanoma cases. Our data support NOTCH inhibition as a promising therapeutic strategy against melanoma. (source: PLoS One. 2011;6(9):e25264. Epub 2011 Sep 29)
(last updated: 4/18/2016).
