BIBO3304 TFA

BIBO3304 TFA has subnanomolar affinity for both the human and the rat neuropeptide Y (NPY) Y1 receptor with IC50 values of 0.38±0.06 nM and 0.72±0.42 nM, respectively ^[1].

BIBO3304 TFA(10 μM, 24h) effectively blocked Geminin upregulation in 10% serum-cultured vascular smooth muscle cells (VSMC) induced by 200 nM NPY ^[2].

BIBO3304 TFA (5 μmol)-treated mice showed a significant increase in whole body bone mineral content after 4- and 8-weeks of treatment, and this effect was not observed in vehicle-treated mice ^[3]. BIBO3304 TFA treatment improved β-cell function and preserved functional β-cell mass, thereby resulting in better glycaemic control in both high-fat-diet/multiple low-dose streptozotocin- and db/db type 2 diabetic mice ^[4]. Periphery specific antagonism of Y1R signalling via the non-brain penetrable Y1R antagonist BIBO3304 TFA prevents diet-induced obesity via stimulating energy expenditure and whole-body thermogenesis ^[5].

References:
[1]. Wieland H A, Engel W, Eberlein W, et al. Subtype selectivity of the novel nonpeptide neuropeptide Y Y1 receptor antagonist BIBO 3304 and its effect on feeding in rodents[J]. British journal of pharmacology, 1998, 125(3): 549-555.
[2]. Jiang Z, Zhou Y, Chen X, et al. Different effects of neuropeptide Y on proliferation of vascular smooth muscle cells via regulation of Geminin[J]. Molecular and cellular biochemistry, 2017, 433(1): 205-211.
[3]. Sousa D M, Baldock P A, Enriquez R F, et al. Neuropeptide Y Y1 receptor antagonism increases bone mass in mice[J]. Bone, 2012, 51(1): 8-16.
[4]. Yang C H, Ann-Onda D, Lin X, et al. Elevated Neuropeptide Y1 Receptor Signaling Contributes to β-cell Dysfunction and Failure in Type 2 Diabetes[J]. bioRxiv, 2021.
[5]. Yan C, Zeng T, Lee K, et al. Peripheral-specific Y1 receptor antagonism increases thermogenesis and protects against diet-induced obesity[J]. Nature communications, 2021, 12(1): 1-20.

BIBO3304 TFA 对人和大鼠神经肽 Y (NPY) Y1 受体具有亚纳摩尔亲和力，IC50 值分别为 0.38±0.06 nM 和 0.72±0.42 nM^[1]。

BIBO3304 TFA（10 μM，24 小时）有效阻断 200 nM NPY ^[2] 诱导的 10% 血清培养的血管平滑肌细胞 (VSMC) 中的 Geminin 上调。

BIBO3304 TFA（5 μmol）处理的小鼠在处理 4 周和 8 周后全身骨矿物质含量显着增加，而在载体处理的小鼠中未观察到这种效果 ^{[3]< /sup>。 BIBO3304 TFA 治疗可改善 β 细胞功能并保留功能性 β 细胞群，从而在高脂肪饮食/多种低剂量链脲佐菌素和 db/db 2 型糖尿病小鼠中实现更好的血糖控制 [4] 。通过不可穿透的 Y1R 拮抗剂 BIBO3304 TFA 对 Y1R 信号的外周特异性拮抗作用可通过刺激能量消耗和全身产热来预防饮食诱导的肥胖[5]。}