Tasisulam (LY573636) is an apoptosis inducer and an antitumor agent via the intrinsic pathway.

Tasisulam在多种人类白血病和淋巴瘤细胞系中抑制生长，ED50值介于7至40μM之间。LY573636还通过丧失线粒体膜电位和诱导活性氧种类的产生，在HL60、Reh和MD901细胞中诱导凋亡。[1]此外，Tasisulam在测试的120种细胞系中70%以上显示出抗增殖活性，EC50值小于50μM。Tasisulam在Calu-6和A-375细胞中诱导G2-M堆积及随后的凋亡。在体外，Tasisulam还能抑制由VEGF、FGF和EGF诱导的内皮细胞索形成，其EC50值分别为47、103和34nM。[2]

Tasisulam在活体内诱导血管正常化的形态特征，包括提高脉络膜细胞覆盖率和降低低氧状态。Tasisulam（25或50 mg/kg, i.v.）显示出剂量依赖性的抗肿瘤活性，能够诱导凋亡并正常化与Calu-6非小细胞肺癌异种移植模型相关的血管。此外，Tasisulam在多种活体内异种移植模型中显示出强大的抗肿瘤活性，包括结直肠癌（HCT-116）、黑色素瘤（A-375）、胃癌（NUGC-3）、白血病（MV-4-11）和胰腺癌（QGP-1）。[2]

Electrophysiology: The human IKCa1 is cloned and expressed in COS-7 cells. Cells are studied in the whole-cell configuration of the patch-clamp technique. The holding potential is 280 mV. The internal pipette solution contains: 145 mM K+ aspartate, 2 mM MgCl2, 10 mM Hepes, 10 mM K2EGTA, and 8.5 mM CaCl2 (1 μM free Ca2+), pH 7.2, 290-310 mOsm. To reduce currents from the native chloride channels in COS-7 cells, Na+ aspartate Ringer is used as an external solution: 160 mM Na+ aspartatey/4.5 mM KCl/2 mM CaCl2/1 mM MgCl2/5 mM Hepes, pH 7.4/290-310 mOsm. IKCa currents in COS-7 cells are elicited by 200-ms voltage ramps from -120 mV to 40 mV applied every 10 seconds and the reduction of slope conductance at -80 mV by TRAM-34 taken as a measure of channel block.

Cells are treated with various concentrations of LY573636. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay is performed. Briefly, MTT is dissolved in phosphate-buffered saline (PBS) at 5 mg/mL. Approximately 1,000 cells per well are incubated in culture medium for 96 hours in 96-well plates; and then, 10 μL of the MTT solution is added. After a 4-hour incubation, 100 μL of solubilization solution (20 % sodium dodecyl sulfate [SDS]) is added, and the mixture was incubated at 37 °C for 16 hours. In this assay, MTT is cleaved to an orange formazan dye by metabolically active cells; and the absorbance of the formazan product is measured with an enzyme-linked immunoabsorbent assay (ELISA) reader at 540 nm. (Only for Reference)