YL-365 is a potent GPR34 antagonist with an IC50 value of 17nM [1]. YL-365 competitively binds to the region of the GPR34 orthosteric binding pocket and induces receptor conformational changes to exert an inhibitory effect [2]. YL-365 is widely used for targeting the ADAM8 gene to inhibit the progression of clear cell renal cell carcinoma[3].
In vivo, YL-365 treatment via intraperitoneal injection at a dose of 20mg/kg (twice a day) for 3 days substantially reduced mechanical allodynia in the mouse model of neuropathic pain with the L4 spinal nerve being cut off [2].
References:
[1] Chakraborty A, Kamat S S. Lysophosphatidylserine: A signaling lipid with implications in human diseases[J]. Chemical reviews, 2024, 124(9): 5470-5504.
[2] Xia A, Yong X, Zhang C, et al. Cryo-EM structures of human GPR34 enable the identification of selective antagonists[J]. Proceedings of the National Academy of Sciences, 2023, 120(39): e2308435120.
[3] Wu Y, Zhang Y, Sun K, et al. Prognostic significance of key immune cell functional alterations in clear cell renal cell carcinoma[J]. Translational Cancer Research, 2025, 14(10): 6364-6387.
YL-365是一种强效的GPR34拮抗剂，IC50值为17nM[1]。YL-365 竞争性结合至GPR34正构结合口袋区域，并诱导受体构象变化以发挥抑制作用[2]。YL-365被广泛用于靶向ADAM8基因，以抑制透明细胞肾细胞癌的进展[3]。
在体内，通过腹腔注射YL-365，剂量为20mg/kg（每日两次），连续3天，显著减轻了L4脊神经切断的神经病理性疼痛小鼠模型中的机械性痛觉超敏[2]。