GDC-2394 是一种口服有效、选择性的 NLRP3 抑制剂，同时也抑制 IL-1β，IC₅₀ 为 0.4 μM (human IL-1β) 和 0.1 μM (mouse IL-1β)。GDC-2394 抑制 NLRP3 诱导的 caspase-1 活性，但不抑制 NLRC4 依赖的炎症小体激活。

GDC-2394 is an orally active and selective NLRP3 inhibitor, and also inhibits IL-1β with IC 50 s of 0.4 μM (human IL-1β) and 0.1 μM (mouse IL-1β). GDC-2394 inhibits NLRP3-induced caspase-1 activity without inhibiting NLRC4-dependent inflammasome activation.

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GDC-2394 (20 μM; 30 min) inhibits NLRP3-induced apoptosis associated speck-like protein containing CARD (ASC) speck formation in THP-1 cells.
GDC-2394 (1 nM-10 μM; 7 d) inhibits human macrophage IL-1β and IL-18 production after activation of the NLRP3 inflammasome.
GDC-2394 (0-20 μM; 30 min) inhibits NLRP3-dependent caspase-1 activation (IC50=51 nM) in THP-1 cells, also inhibits NLRP3-dependent IL-1β release (IC50=63 nM) and NLRC4-dependent IL-1β release (IC50>20 μM) in mouse bone marrow-derived macrophages (mBMDMs).
has not independently confirmed the accuracy of these methods. They are for reference only.

GDC-2394 (compound 20) (1 mg/kg, 10 mg/kg; p.o.; single dose) inhibits production of IL-1β in an acute mouse peritonitis model.
GDC-2394 (25 mg/kg; once daily for 7 d) reduces paw swelling and pain in a functional rat model of gouty arthritis.

Preclinical PK of GDC-2394.
Species Mouse Rat

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；In solvent -80°C 6 months

[1]. McBride C, et al. Overcoming Preclinical Safety Obstacles to Discover (S)-N-((1,2,3,5,6,7-Hexahydro-s-indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonamide (GDC-2394): A Potent and Selective NLRP3 Inhibitor. J Med Chem. 2022 Oct 24.
[2]. Stafford, et al. Preparation of hexahydroindacenylcarbamoyldihydropyrazolooxazinesulfonamide derivatives and analogs for use as interleukin-1 activity inhibitors: World Intellectual Property Organization, WO2018136890[P]. 2018-07-26.

In Vitro: DMSO : 50 mg/mL (115.87 mM; ultrasonic and warming and heat to 60°C)配制储备液