DIDS is an anion transport inhibitor, which inhibits the ClC-Ka chloride channel with an IC50 of 100 μM and the bacterial ClC-ec1Cl-/H+ exchanger with an IC50 of ~300 μM. [1]
Chloride channels are a superfamily consisting of approximately 13 subgroups and display a variety of functions in physiology. The human genome contains nine CLC proteins, which serve various physiological functions and potentially constitute novel exciting drug targets for the treatment of hypertension, osteoporosis, and gastrointestinal and renal disorders. [1]
DIDS's effect on the calcium-activated chloride current [ICl (ca)] in muscle cells from the rabbit portal vein was studied with the perforated patch technique. Consequently, DIDS reduced the amplitude of spontaneous transient inward currents (STICs) in a concentration-dependent manner with an IC50 value of 2.1 x 10-4 M for STICs. Moreover, DIDS was investigated for its action on contraction of cerebral artery smooth muscle cells. DIDS showed a vasodilator effect on pressure-constricted arteries with IC50 of 69 ± 14 μM. [2, 3]
In vivo study showed DIDS alone increased the effect of hyperthermia at 42.5 ℃ or 43.5 ℃ to suppress tumor growth. The thermosensitization was greater when DIDS was combined with amiloride. Hyperthermia at 43.5 ℃ could result in a tumor growth delay for 4 days, while hyperthermia and treatment of 25 mg/kg DIDS prolonged the delay to approximately 6 days. As a proof, in vivo-in vitro excision assays for cell survival illustrated that DIDS enhanced the heat-induced tumor cell death. [4]
References:
[1] Wulff, Heike. "New light on the “Old” chloride channel blocker DIDS." ACS chemical biology 3.7 (2008): 399-401.
[2] Hogg, R. C., Q. Wang, and W. A. Large. "Effects of Cl channel blockers on Ca‐activated chloride and potassium currents in smooth muscle cells from rabbit portal vein." British journal of pharmacology 111.4 (1994): 1333-1341.
[3] Nelson, Mark T., et al. "Chloride channel blockers inhibit myogenic tone in rat cerebral arteries." The Journal of Physiology 502.2 (1997): 259-264.
[4] Lyons, John C., Brian D. Ross, and Chang W. Song. "Enhancement of hyperthermia effect in vivo by amiloride and DIDS." International Journal of Radiation Oncology* Biology* Physics 25.1 (1993): 95-103.
DIDS 是一种阴离子转运抑制剂,可抑制 ClC-Ka 氯离子通道,IC50 为 100 μM 和细菌 ClC-ec1Cl-/H+ 交换器,IC50 约为 300 μM。 [1]
氯离子通道是一个由大约13个亚群组成的超家族,在生理学上发挥着多种功能。人类基因组包含九种 CLC 蛋白,它们具有多种生理功能,并可能构成治疗高血压、骨质疏松症以及胃肠道和肾脏疾病的新型药物靶点。 [1]
采用穿孔补片技术研究了DIDS对兔门静脉肌肉细胞中钙激活氯化物电流[ICl(ca)]的影响。因此,DIDS 以浓度依赖性方式降低了自发瞬态内向电流 (STIC) 的振幅,STIC 的 IC50 值为 2.1 x 10-4 M。此外,研究了DIDS对大脑动脉平滑肌细胞收缩的作用。 DIDS 显示出对压力收缩动脉的血管扩张作用,IC50 为 69 ±； 14 &亩;M. [2, 3]
体内研究显示单独使用DIDS可增加42.5℃或43.5℃热疗抑制肿瘤生长的效果。当 DIDS 与阿米洛利联合使用时,热敏化作用更大。 43.5 ℃ 的热疗可导致肿瘤生长延迟 4 天,而热疗和 25 mg/kg DIDS 治疗将延迟延长至约 6 天。作为证据,细胞存活的体内-体外切除试验表明 DIDS 增强了热诱导的肿瘤细胞死亡。 [4]