GDC-0310 is a selective acylsulfonamide voltage-gated sodium channel 1.7 (NaV1.7) inhibitor with an IC50 value of 0.6nM[1]. NaV1.7 is a complex protein with multiple druggable sites that plays a vital role in the transmission of pain signals[2]. GDC-0310 is an orally available small molecule NaV1.7 inhibitor that can be used to treat pain[3, 4]. Compared with GDC-0276 (Catalog No.: GC39559), GDC-0310 exhibits better metabolic stability, NaV selectivity and pharmacokinetic characteristics[5].
References:
[1] Safina B S, McKerrall S J, Sun S, et al. Discovery of acyl-sulfonamide NaV1. 7 inhibitors GDC-0276 and GDC-0310[J]. Journal of medicinal chemistry, 2021, 64(6): 2953-2966.
[2] McKerrall S J, Sutherlin D P. Nav1. 7 inhibitors for the treatment of chronic pain[J]. Bioorganic & medicinal chemistry letters, 2018, 28(19): 3141-3149.
[3] Stevens E B, Stephens G J. Recent advances in targeting ion channels to treat chronic pain[J]. British journal of pharmacology, 2018, 175(12): 2133.
[4] Stumpf A, Cheng Z K, Beaudry D, et al. Improved synthesis of the Nav1. 7 inhibitor GDC-0276 via a highly regioselective SNAr reaction[J]. Organic Process Research & Development, 2019, 23(9): 1829-1840.
[5] Asiri Y I, Hassan M Z. An Overview of Ion Channels Therapeutics in the Treatment of Pain[J]. Arabian Journal of Chemistry, 2023: 105180.
GDC-0310是选择性酰基磺酰胺电压门控型钠离子通道1.7（NaV1.7）抑制剂，IC50值为0.6nM[1]。NaV1.7是一种具有多个成药位点的复杂蛋白质，在疼痛信号的传递中起着至关重要的作用[2]。GDC-0310是一种口服小分子NaV1.7抑制剂，能够用于治疗疼痛[3, 4]。与GDC-0276（目录号：GC39559）相比，GDC-0310表现出更好的代谢稳定性、NaV选择性和药代动力学特征[5]。