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GDC-0334

Chemical Structure : GDC-0334

CAS No.: 1984824-54-5

GDC-0334 (GDC0334)

Catalog No.: PC-72460Not For Human Use, Lab Use Only.

GDC-0334 (GDC0334) is a highly potent, selective, orally bioavailable TRPA1 antagonist with IC50 of 1.7 nM in cell-based assays.

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    Biological Activity

    GDC-0334 (GDC0334) is a highly potent, selective, orally bioavailable TRPA1 antagonist with IC50 of 1.7 nM in cell-based assays.
    GDC-0334 demonstrated potent TRPA1 inhibition in several species, including human (IC50=1.7 nM), cynomolgus (IC50=3.6 nM), mouse (IC50=2.7 nM), guinea pig (IC50=11.1 nM), and dog (IC50=102 nM).
    GDC-0334 displays good selectivity against human TRPV1, TRPM8, and TRPC6 (all IC50s>10 uM).
    GDC-0334 also inhibits calcium flux in human primary cells, HASMCs and HLFs, treated with the TRPA1 agonist AITC.
    GDC-0334 suppresses AITC-induced edema in vivo in rat (1-10 mg/kg), reduces OVA-induced asthma model in rats and guinea pigs and guinea pig model of cough.
    GDC-0334 is a potent inhibitor of AITC-induced dermal blood flow (DBF) in vivo in rats and guinea pigs, reduces AITC-induced perfusion and nocifensive behavior in rats and itch and pain scores in humans.

    Physicochemical Properties

    M.Wt 609.495
    Formula C24H19F8N5O3S
    Appearance Solid
    CAS No.
    Storage
    Solide Powder
    -20°C 12 Months; 4°C 6 Months
    In Solvent
    -80°C 6 Months; -20°C 6 Months
    Shipping
    Solubility

    10 mM in DMSO

    Chemical Name/SMILES

    (2S,4R,5S)-4-fluoro-1-((4-fluorophenyl)sulfonyl)-5-methyl-N-((5-(trifluoromethyl)-2-(2-(trifluoromethyl)pyrimidin-5-yl)pyridin-4-yl)methyl)pyrrolidine-2-carboxamide

    References

    1. Balestrini A, et al. J Exp Med. 2021 Apr 5;218(4):e20201637.

    2. Chan P, et al. Clin Transl Sci. 2021 Sep;14(5):1945-1954.

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