Barbadin
目录号 : GC38351
Barbadin是β-arrestin/β2-adaptin之间相互作用的选择性抑制剂，对β-arrestin1和β-arrestin2的IC50值分别为19.1μM和15.6μM。
Cas No.:356568-70-2
Sample solution is provided at 25 µL, 10mM.
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Barbadin is a selective inhibitor of the β-arrestin/β2-adaptin interaction, with IC50 values of 19.1μM and 15.6μM for β-arrestin1 and β-arrestin2, respectively. Barbadin exerts its inhibitory effect by blocking the internalization of β2-adrenergic receptors, V2 vasopressin (V2R), and angiotensin II type 1 (AT1R) receptors[1,2]. Barbadin is commonly used in studies investigating neutrophil function modulation, G protein-coupled receptor (GPCR) internalization, and related signaling pathways[3,4].
In vitro, pretreatment of HEK293T cells with Barbadin (50μM) for 30min completely blocked V2R agonist arginine vasopressin (AVP)-induced ERK1/2 phosphorylation, but did not affect epidermal growth factor (EGF)-induced ERK activation[1]. Pretreatment of MDA-MB-231 cells with Barbadin (100μM) for 30min, followed by AVP stimulation for 45min, significantly increased the level of the autophagy marker LC3II[5]. Pretreatment of HEK293 cells expressing wild-type μ-opioid receptor (MOR1) with Barbadin (100μM) for 15 or 30min significantly inhibited DAMGO (10μM)-induced receptor internalization and MAPK signaling pathway activation[6]. Treatment of goldfish pituitary cells via a cell column perifusion system with Barbadin (25μM) for 65min significantly increased basal growth hormone secretion levels, but had no sustained effect on basal luteinizing hormone secretion[7].
In vivo, bilateral injection of Barbadin (300ng/side) via pre-implanted cannulas into the dorsal striatum of a tardive dyskinesia (TD) mouse model induced by long-term oral haloperidol (2mg/kg/day; 21 days) blocked the ameliorative effect of the A2A receptor agonist CGS 21680A (1ng/side) on vacuous chewing movements (VCMs)[8].
References:
[1] BEAUTRAIT A, PARADIS J S, ZIMMERMAN B, et al. A new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling[J]. Nature communications, 2017, 8(1): 15054.
[2] HESSIEN M, DONIA T, TABLL A A, et al. Mechanistic-based classification of endocytosis-related inhibitors: does it aid in assigning drugs against SARS-CoV-2?[J]. Viruses, 2023, 15(5): 1040.
[3] SUNDQVIST M, HOLDFELDT A, WRIGHT S C, et al. Barbadin selectively modulates FPR2-mediated neutrophil functions independent of receptor endocytosis[J]. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 2020, 1867(12): 118849.
[4] HE Y, LIU H, YIN N, et al. Barbadin potentiates long-term effects of lorcaserin on POMC neurons and weight loss[J]. Journal of Neuroscience, 2021, 41(26): 5734-5746.
[5] DONIA T, ABOUDA M, KELANY M, et al. β-Arrestin inhibition induces autophagy, apoptosis, G0/G1 cell cycle arrest in agonist-activated V2R receptor in breast cancer cells[J]. Medical Oncology, 2021, 38(4): 38.
[6] SHIRAKI A, SHIMIZU S. The molecular associations in clathrin-coated pit regulate β-arrestin-mediated MAPK signaling downstream of μ-opioid receptor[J]. Biochemical and Biophysical Research Communications, 2023, 640: 64-72.
[7] KHALID E, CHANG J P. β-Arrestin-dependent signaling in GnRH control of hormone secretion from goldfish gonadotrophs and somatotrophs[J]. General and Comparative Endocrinology, 2020, 287: 113340.
[8] NAGAOKA K, ASAOKA N, NAGAYASU K, et al. Enhancement of adenosine A2A signaling improves dopamine D2 receptor antagonist-induced dyskinesia via β-arrestin signaling[J]. Frontiers in Neuroscience, 2023, 16: 1082375.
Barbadin是β-arrestin/β2-adaptin之间相互作用的选择性抑制剂，对β-arrestin1和β-arrestin2的IC50值分别为19.1μM和15.6μM。Barbadin通过阻断β2-肾上腺素能受体、V2血管加压素（V2R）和血管紧张素 II 1 型（AT1R）受体的内吞作用实现抑制[1,2]。Barbadin通常用于中性粒细胞功能调节及G蛋白偶联受体（GPCR）内化和相关信号通路的研究[3,4]。
在体外，Barbadin（50μM）预处理HEK293T细胞30min，完全阻断了V2R激动剂精氨酸加压素（AVP）诱导的ERK1/2磷酸化，但不影响表皮生长因子（EGF）诱导的ERK激活[1]。Barbadin（100μM）预处理MDA MB-231细胞30min，随后用AVP刺激45min，显著增加了自噬标志物LC3II的水平[5]。Barbadin（100μM）预处理表达野生型μ-阿片受体（MOR1）的HEK293细胞15或30min，显著抑制了由DAMGO（10μM）诱导的受体内化和MAPK信号通路激活[6]。Barbadin（25μM）通过细胞柱灌流系统处理金鱼垂体细胞65min，显著提高了基础生长激素的分泌水平，但对基础促黄体生成素分泌无持续性影响[7]。
在体内，Barbadin（300ng/side）通过预植入的导管双侧注射到长期口服氟哌啶醇（2mg/kg/day; 21 days）诱导的迟发性运动障碍（TD）小鼠模型的背侧纹状体中，阻断了A2A受体激动剂CGS 21680A（1ng/side）对空洞咀嚼运动（VCMs）的改善作用[8]。
| Cell experiment [1]: | |
Cell lines | HEK293T cells |
Preparation Method | HEK293T cells were pretreated with Barbadin (50μM) for 30min, followed by stimulation with AVP (100nM) or EGF (100ng/mL) for the indicated times. Lysates were resolved on a 10% SDS-PAGE and analysed by western blot using anti-phospho-ERK1/2 (1:1000) and anti-total-ERK1/2 (1:2000). Signals from western blots were determined by densitometry analysis using the Image J software. |
Reaction Conditions | 50μM; 30min |
Applications | Barbadin completely blocked the AVP-stimulated ERK1/2 activation. This effect was selective since Barbadin did not block EGF-stimulated ERK1/2. |
| Animal experiment [2]: | |
Animal models | Tardive dyskinesia (TD) mouse model |
Preparation Method | Mice were orally administered haloperidol (2mg/kg/day) daily for 21 days. On day 22, VCMs were counted for 5min as an initial baseline before the mice received CGS 21680A + Barbadin (300ng/side) through a pre-implanted cannula in their dorsal striatum. Five minutes after the injection, the VCMs were counted for another 5min to determine the effect of the injected drug. Daily haloperidol treatment was continued for 8 more days; on day 26 and 30, the second and third sets of VCM measurements were taken in a crossover design. |
Dosage form | 300ng/side; bilateral infusion; microinjection |
Applications | The number of VCMs decreased after bilateral infusion of CGS 21680A (1ng/side), when compared with the vehicle-infused mice, whereas this effect was abolished upon co-administration of CGS 21680A and Barbadin (300ng/side). |
References: | |
| Cas No. | 356568-70-2 | SDF | |
| Canonical SMILES | O=C1C(C(C2=CC=C(CC3=CC=CC=C3)C=C2)=CS4)=C4N=CN1N | ||
| 分子式 | C19H15N3OS | 分子量 | 333.41 |
| 溶解度 | DMSO: 50 mg/mL (149.97 mM) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.9993 mL | 14.9966 mL | 29.9931 mL |
| 5 mM | 599.9 μL | 2.9993 mL | 5.9986 mL |
| 10 mM | 299.9 μL | 1.4997 mL | 2.9993 mL |
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