SCH 202676 hydrobromide is an allosteric modulator with good solubility and stability that inhibits the binding of both agonists and antagonists to a variety of G-protein coupled receptors (GPCRs)[1,2]. SCH 202676 hydrobromide effectively inhibits the function of multiple GPCRs, including adenosine, opioid, and adrenergic receptors, and is commonly used in the study of GPCR-mediated cellular signaling[1,3].
In vitro, pretreatment of M1 CHO cells with SCH 202676 hydrobromide (1-100μM) for 15min, followed by co-incubation with acetylcholine (ACh) for 30min, caused progressive dextral displacements of the ACh concentration-response (C-R) curve and significantly reduced the Emax of ACh at a high concentration (100μM)[4]. Treatment of Wistar rat brain slices with SCH 202676 hydrobromide (10μM) for 90min resulted in increased non-specific [35S]GTPγS binding in the absence of DTT[5]. Pretreatment of MEG01 cells with SCH 202676 hydrobromide (1μM) for 30min significantly reduced the dynamic mass redistribution (DMR) signal response induced by phenylacetylglutamine (PAGln)[6]. Pretreatment of rat round spermatids with SCH 202676 hydrobromide (1μM) for 5min significantly attenuated the arachidonic acid (AA)-induced increase in intracellular calcium ([Ca2+]i)[7].
In vivo, abdominal injection of SCH 202676 hydrobromide (10μM) in male Rhodnius prolixus adults for 30min significantly increased the contraction frequency of the aorta[8].
References:
[1] FAWZI A B, MACDONALD D, BENBOW L L, et al. SCH-202676: an allosteric modulator of both agonist and antagonist binding to G protein-coupled receptors[J]. Molecular Pharmacology, 2001, 59(1): 30-37.
[2] CASTRO A, CASTAÑO T, ENCINAS A, et al. Advances in the synthesis and recent therapeutic applications of 1, 2, 4-thiadiazole heterocycles[J]. Bioorganic & Medicinal Chemistry, 2006, 14(5): 1644-1652.
[3] GAO Z G, GROSS A S, JACOBSON K A. Effects of the allosteric modulator SCH-202676 on adenosine and P2Y receptors[J]. Life Sciences, 2004, 74(25): 3173-3180.
[4] LANZAFAME A, CHRISTOPOULOS A. Investigation of the interaction of a putative allosteric modulator, N-(2, 3-diphenyl-1, 2, 4-thiadiazole-5-(2 H)-ylidene) methanamine hydrobromide (SCH-202676), with M1 muscarinic acetylcholine receptors[J]. The Journal of Pharmacology and Experimental Therapeutics, 2004, 308(3): 830-837.
[5] LEWANDOWICZ A M, VEPSÄLÄINEN J, LAITINEN J T. The ‘allosteric modulator’ SCH‐202676 disrupts G protein‐coupled receptor function via sulphydryl‐sensitive mechanisms[J]. British Journal of Pharmacology, 2006, 147(4): 422-429.
[6] NEMET I, SAHA P P, GUPTA N, et al. A cardiovascular disease-linked gut microbial metabolite acts via adrenergic receptors[J]. Cell, 2020, 180(5): 862-877.
[7] PAILLAMANQUE J, SANCHEZ-TUSIE A, CARMONA E M, et al. Arachidonic acid triggers [Ca2+]i increases in rat round spermatids by a likely GPR activation, ERK signalling and ER/acidic compartments Ca2+ release[J]. PLoS One, 2017, 12(2): e0172128.
[8] VILLALOBOS SAMBUCARO M J, ALZUGARAY M E, RONDEROS J R. Mechanisms controlling haemolymph circulation under resting conditions in the Chagas disease vector Rhodnius prolixus[J]. Journal of Experimental Biology, 2024, 227(15): jeb247801.
SCH 202676 hydrobromide是一种具有良好溶解性、稳定性和对多种G蛋白偶联受体（GPCRs）的激动剂和拮抗剂结合有抑制作用的变构调节剂[1,2]。SCH 202676 hydrobromide能够有效抑制腺苷受体、阿片类受体、肾上腺素能受体在内的多种GPCR功能，常被用于GPCR介导的细胞信号传导研究[1,3]。
在体外，SCH 202676 hydrobromide（1-100μM）预处理M1 CHO细胞15min，随后与乙酰胆碱（ACh）共孵育30min，引起ACh 浓度-反应（C-R）曲线右移，并在高浓度（100μM）下显著降低ACh的Emax值[4]。SCH 202676 hydrobromide（10μM）处理Wistar大鼠脑切片90min，在无DTT条件下引起非特异性[35S]GTP γS结合增加[5]。SCH 202676 hydrobromide（1μM）预处理MEG01细胞30min，显著降低了苯乙酰谷氨酰胺（PAGln）诱导的动态质量重置（DMR）信号响应[6]。SCH 202676 hydrobromide（1μM）预处理大鼠圆形精子细胞5min，显著降低了由花生四烯酸（AA）诱导的胞内钙离子（[Ca2+]i）增加[7]。
在体内，SCH 202676 hydrobromide（10μM）通过腹部注射处理雄性Rhodnius prolixus成虫30min，Rhodnius prolixus的主动脉收缩频率显著增加[8]。