SQ 22536

SQ 22536 is a potent adenylate cyclase (AC) inhibitor^[1]. SQ 22536 can be widely used in various studies to elucidate the role of cAMP signaling pathways in many physiological and pathological processes^{[2, 3]}. SQ 22536 can block dopamine-induced decreases in cyclin E, cyclin-dependent protein kinase-2 (CDK-2), cyclin D1, and CDK-4^[4].

In vitro, treatment of human acute myeloid leukemia (AML) KG-1 cells with SQ 22536 (100µM) for 24h reversed the inhibitory effects of polydatin on KG-1 cell proliferation, migration, and invasion^[5]. Pretreatment of Schwann cells with SQ 22536 (100µM) for 1h abolished the calcitonin gene-related peptide (CGRP)-mediated increase in IL-1β^[6].

In vivo, SQ 22536 (1nmol/kg) was injected intraperitoneally to treat epilepsy model mice. The use of SQ 22536 alone or in combination with dipyridamole or BRL50481 significantly improved the anticonvulsant activity, with the protection rates increasing by 83.3%, 66.7% and 50%, respectively^[7].

References:
[1] Emery A C, Eiden M V, Eiden L E. A new site and mechanism of action for the widely used adenylate cyclase inhibitor SQ22,536[J]. Molecular pharmacology, 2013, 83(1): 95-105.
[2] Alasbahi R H, Melzig M F. Forskolin and derivatives as tools for studying the role of cAMP[J]. Die Pharmazie-An International Journal of Pharmaceutical Sciences, 2012, 67(1): 5-13.
[3] Khan H, Tiwari C, Grewal A K, et al. Pharmacological modulation of phosphodiesterase-7 as a novel strategy for neurodegenerative disorders[J]. Inflammopharmacology, 2022, 30(6): 2051-2061.
[4] Lee M Y, Heo J S, Han H J. Dopamine regulates cell cycle regulatory proteins via cAMP, Ca2+/PKC, MAPKs, and NF‐κB in mouse embryonic stem cells[J]. Journal of cellular physiology, 2006, 208(2): 399-406.
[5] Min H U A, Weili Z. Effects of polydatin on the cell proliferation, migration, invasion and tumor growth of AML[J]. China Pharmacy, 2024, 35(6): 701-706.
[6] Permpoonputtana K, Porter J E, Govitrapong P. Calcitonin gene-related peptide mediates an inflammatory response in Schwann cells via cAMP-dependent ERK signaling cascade[J]. Life sciences, 2016, 144: 19-25.
[7] Nandhakumar J, Tyagi M G. Evaluation of seizure activity after phospho-diesterase and adenylate cyclase inhibition (SQ22536) in animal models of epilepsy[J]. Indian J Sci Technol, 2010, 3(7): 710-717.

SQ 22536是一种有效的腺苷酸环化酶（AC）抑制剂^[1]。SQ 22536能够广泛用于各种研究，以阐明cAMP信号通路在许多生理和病理过程中的作用^{[2, 3]}。SQ 22536能够阻断多巴胺诱导的细胞周期蛋白E、细胞周期蛋白依赖性蛋白激酶-2（CDK-2）和细胞周期蛋白D1、CDK-4的降低^[4]。

在体外，SQ 22536（100µM）处理人急性髓系白血病（AML）KG-1细胞24h，逆转了虎杖苷（polydatin）对KG-1细胞增殖、迁移、侵袭的抑制作用^[5]。SQ 22536（100µM）预处理Schwann细胞1h，消除了降钙素基因相关肽（CGRP）介导的IL-1β增加^[6]。

在体内，SQ 22536（1nmol/kg）通过腹腔注射治疗癫痫模型小鼠，单独使用SQ 22536、SQ 22536与dipyridamole或BRL50481联合使用均大大提高了抗惊厥活性，保护率分别提高了83.3%、66.7%和50%^[7]。