MAT2A Inhibitor II, FIDAS-5

A cell-permeable fluorinated N,N-dialkylaminostilbene (FIDAS) analogue of FIDAS-3 that is >2-fold more potent than FIDAS-3 in inhibiting MAT2A-catalyzed SAM (S-adenosylmethionine) synthesis both in cell-free (IC₅₀ = 2.1 µM with FIDAS-5 vs. 4.9 µM with FIDAS-3; [L-Met] = [ATP] = 1 mM, [MAT2A] = 10 µg/mL; 20 min FIDAS preincubation prior to 30 min reaction) and cell-based (64% and 56% decrease of SAM and SAH level, respectively, in LS174T cells after 36 h treatment with either 3 µM FIDAS-5 or 10 µM FIDAS-3) assays. FIDAS-5 at 3 µM is shown to completely inhibit the proliferation of LS174T CRC (colorectal cancer) for up to 7 d in vitro and, when administered orally, effectively suppress HT29 CRC tumor expansion in mice in vivo (by 58% on d 18 post HT29 xenograft; 20 mg/kg/day starting d 4). Computer-aided in silico modeling predicts that FIDAS-3 & -5 target SAM-binding pocket at the interface of MAT2A dimer and in vitro binding studies reveals FIDAS-3 effectively competes against SAM for MAT2A binding.

Cell permeable: yes

Primary Target
MAT2A

Reversible: yes

Packaged under inert gas

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Zhang, W., et al. 2013. ACS Chem. Biol.8, 796.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)