BB-Cl-Amidine

BB-Cl-Amidine, a peptidylarginine deminase (PAD) inhibitor, is frequently used to study PAD function.^[1]

In vitro experiment it shown that after 48 h of treatment with 0 to 20 μM BB-Cl-Amidine caused a dose-dependent decrease in cell viability in canine and feline mammary tumor cells.^[1] In vitro, Cl-amidine and BB-Cl-Amidine show similar potencies and selectivities in U2OS cells, the cellular potency of BB-Cl-Amidine is increased by more than 20-fold, with EC50 values of 8.8±0.6 μM in U2OS osteosarcoma cells.^[5]

In vivo efficacy test it exhibited that treatment with 1 μg/ml BB-Cl-Amidine intraperitoneally for two weeks in xenograft mice, BB-Cl-Amidine-treated tumors became crusty and the surrounding skin showed hair loss. There was an or a slight increase in apoptotic cells in the BB-Cl-Amidine-treated canine or feline xenograft tumors.^[1] In vitro, at concentrations around 15-20 μM and 4 μM, respectively, BB-Cl-Amidine inhibited both PAD isoforms in a dose-dependent manner with 90% inhibition of PAD2 and PAD4.^[2]

In vivo, arthritic mice were treated with 10 mg/kg BB-Cl-Amidine, there was a reduction in inflammation and joint destruction.^[3] In vivo, treatment with 1 mg/kg BB-Cl-Amidine intraperitoneally and Ac-YVAD-cmk (a pyroptosis inhibitor) attenuated NET levels in BALF and neutrophil infiltration in alveoli. ^[4] In vivo, treatment with 1 mg/kg BB-Cl-Amidine subcutaneously obviously reduced splenomegaly in MRL/lpr mice and improved endothelium-dependent vasorelaxation.^[5]

References:
[1] Ledet MM, et al. BB-Cl-Amidine as a novel therapeutic for canine and feline mammary cancer via activation of the endoplasmic reticulum stress pathway. BMC Cancer. 2018 Apr 12;18(1):412.
[2] Martín Monreal MT, et al. Applicability of Small-Molecule Inhibitors in the Study of Peptidyl Arginine Deiminase 2 (PAD2) and PAD4. Front Immunol. 2021 Oct 19;12:716250.
[3] Kawalkowska J, et al. Abrogation of collagen-induced arthritis by a peptidyl arginine deiminase inhibitor is associated with modulation of T cell-mediated immune responses. Sci Rep. 2016 May 23;6:26430.
[4] Li H, Li Y, et al. Neutrophil Extracellular Traps Augmented Alveolar Macrophage Pyroptosis via AIM2 Inflammasome Activation in LPS-Induced ALI/ARDS. J Inflamm Res. 2021 Sep 21;14:4839-4858.
[5] Knight JS, et al. Peptidylarginine deiminase inhibition disrupts NET formation and protects against kidney, skin and vascular disease in lupus-prone MRL/lpr mice. Ann Rheum Dis. 2015 Dec;74(12):2199-206.

BB-Cl-Amidine 是一种肽基精氨酸脱氨酶 (PAD) 抑制剂，常用于研究 PAD 功能。^[1]

体外实验表明，在用 0 至 20 μM BB-Cl-Amidine 处理 48 小时后，犬和猫乳腺肿瘤细胞的细胞活力呈剂量依赖性降低。^[1] 在体外，Cl-amidine 和 BB-Cl-Amidine 在 U2OS 细胞中表现出相似的效力和选择性，BB-Cl-Amidine 的细胞效力增加超过 20 倍，在 U2OS 中的 EC50 值为 8.8±0.6 μM骨肉瘤细胞.^[5]

体内药效试验表明，在异种移植小鼠中用 1 μg/ml BB-Cl-Amidine 腹腔注射两周，BB-Cl-Amidine 处理的肿瘤变得结痂，周围皮肤出现脱发。在 BB-Cl-Amidine 处理的犬科动物或猫科动物异种移植肿瘤中，凋亡细胞有所增加或略有增加。^[1] 在体外，浓度分别约为 15-20 μM 和 4 μM , BB-Cl-Amidine 以剂量依赖性方式抑制两种 PAD 亚型，对 PAD2 和 PAD4 的抑制率为 90%。^[2]

在体内，用 10 mg/kg BB-Cl-Amidine 治疗关节炎小鼠，炎症和关节破坏减少。^[3] 在体内，用 1 mg/kg 治疗腹膜内注射 BB-Cl-脒和 Ac-YVAD-cmk（一种细胞焦亡抑制剂）可减弱 BALF 中的 NET 水平和肺泡中的中性粒细胞浸润。 ^[4] 在体内，皮下注射 1 mg/kg BB-Cl-Amidine 可显着减少 MRL/lpr 小鼠的脾肿大并改善内皮依赖性血管舒张。^[5]