RO4929097 --- γ-Secretase Inhibitor

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.

Product information

CAS Number: 847925-91-1

Molecular Weight: 469.40

Formula: C22H20F5N3O3

Chemical Name: 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

Smiles: CC(C)(C(=O)N[C@H]1C2=CC=CC=C2C2=CC=CC=C2NC1=O)C(=O)NCC(F)(F)C(F)(F)F

InChiKey: OJPLJFIFUQPSJR-INIZCTEOSA-N

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

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 100 mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

RO4929097 was used at 1-10 µM in vitro.

In Vivo:

RO4929097 was administered orally at 10 mg/kg with an intermittent or daily schedule and showed anti-tumor activity in multiple tumor xenograft models.

References:

1. Luistro L, et al. Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties. (2009) Cancer Res. 69(19):7672-80.
2. He W, et al. High tumor levels of IL6 and IL8 abrogate preclinical efficacy of the γ-secretase inhibitor, RO4929097. (2011) Mol Oncol. 5(3):292-301.
3. Huynh C, et al. The novel gamma secretase inhibitor RO4929097 reduces the tumor initiating potential of melanoma. (2011) PLoS One. 6(9):e25264.

Products are for research use only. Not for human use.