| 名稱 | PAC-1 |
| 描述 | PAC-1 (Procaspase activating compound 1) has been used in trials studying the treatment of Lymphoma, Melanoma, Solid Tumors, Breast Cancer, and Thoracic Cancers, among others. |
| 細(xì)胞實(shí)驗(yàn) | Cells are exposed to various concentrations of PAC-1 for 72 hours. Cell death is quantified by the addition of MTS/PMS CellTiter 96 Cell Proliferation Assay reagent. The plates are incubated at 37 °C for approximately 1 hour (until the colored product formed), and the absorbance is measured at 490 n(Only for Reference) |
| 激酶實(shí)驗(yàn) | In vitro procaspase-3 activation: Procaspase-3 is expressed and purified in Escherichia coli. Various concentrations of PAC-1 are added to 90 μL of a 50 ng/mL of procaspase-3 in caspase assay buffer in a 96-well plate, The plate is incubated for 12 hours at 37 °C. A 10 μL volume of a 2 mM solution of caspase-3 peptidic substrate acetyl Asp-Glu-Val-Asp-p-nitroanilide (Ac-DEVD-pNa) in caspase assay buffer is then added to each well. The plate is read every 2 minutes at 405 nm for 2 hours in a Spectra Max Plus 384 well plate reader. The slope of the linear portion for each well is determined, and the relative increase in activation from untreated control wells is calculated. |
| 體外活性 | PAC-1由于激活procaspase-3和隨后誘導(dǎo)凋亡發(fā)揮體內(nèi)抗腫瘤效果,與體外活性一致.用5 mg的穩(wěn)定釋放低劑量PAC-1處理小鼠,明顯抑制ACHN腎移植瘤生長(zhǎng).用50或100 mg/kg PAC-1口服處理,明顯劑量依賴性阻礙NCI-H226肺癌移植瘤生長(zhǎng),且明顯阻止癌細(xì)胞浸潤(rùn)肺組織. |
| 體內(nèi)活性 | PAC-1能夠以延遲的方式誘導(dǎo)Bax/Bak雙敲除細(xì)胞和Bcl-2和Bcl-xL過表達(dá)細(xì)胞中的細(xì)胞死亡,具有與野生型對(duì)應(yīng)物相同的功效。PAC-1按caspase-3 非依賴性方式誘導(dǎo)細(xì)胞色素c釋放,隨后觸發(fā)下游caspase-3激活和細(xì)胞死亡。PAC-1不能誘導(dǎo)Apaf-1敲除細(xì)胞中的細(xì)胞死亡和半胱天冬酶-3激活,這表明凋亡體形成對(duì)于通過PAC-1介導(dǎo)的細(xì)胞死亡的胱天蛋白酶-3激活是必需的。PAC-1誘導(dǎo)原發(fā)性癌細(xì)胞凋亡,IC50值為3 nM至1.41 μM,比鄰近的非癌細(xì)胞更有效,IC50為5.02 μM至9.98 μM,這也與procaspase-3的濃度直接相關(guān)。PAC-1激活procaspase-3,產(chǎn)生caspase-3,EC50為 0.22 μM,且激活procaspase-7,EC50為 4.5 μM。癌細(xì)胞系中增高的caspase 3水平使 PAC-1 選擇性誘導(dǎo)凋亡,按與procaspase-3 濃度成比例的方式,NCI-H226細(xì)胞的IC50為0.35 μM,UACC-62細(xì)胞的IC50為約3.5 μM。PAC-1通過螯合鋅離子來激活胱天蛋白酶-3,從而減輕鋅介導(dǎo)的抑制作用,并允許胱天蛋白酶原-3自身激活為胱天蛋白酶-3。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | 1eq. HCl : 29.4 mg/mL (75 mM)
DMSO : 55 mg/mL (140.13 mM)
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| 關(guān)鍵字 | Autophagy | Inhibitor | Caspase | Procaspase activating compound-1 | PAC1 | Apoptosis | inhibit | PAC-1 | PAC 1 | Procaspase activating compound1 |
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