| Bioactivity | PAC-1 is a procaspase-3 activator that induces apoptosis in cancer cells with an EC50 of 2.08 μM. | ||||||||||||
| Invitro | PAC-1 activates procaspase-3 with an EC50 of 2.08 μM. PAC-1 exhibits an enhanced zinc chelating ability (EC50= 7.08 μM). PAC-1 induces leukemia cell death with IC50 of 4.03 μM, which is consistent with the values reported by other investigators. PAC-1 treatment also results in death of other malignant cells in a concentration-dependent manner with IC50s ranging from 4.03 to 53.44μM. The overall mean IC50 in the fifteen malignant cell lines is 0.88 mM for WF-210 and 19.40 μM for PAC-1. In contrast, the sensitivity of the normal human cells (PBL, L-02, HUVEC and MCF 10A) to WF-210 is 2.6-fold lower (mean IC50=412.34 μM) than PAC-1 (mean IC50=158.29 μM)[1]. Procaspase-activating compound-1 (PAC-1) is the first direct caspase-activating compound discovered. PAC-1 treatment upregulates Ero1α in multiple cell lines, whereas silencing of Ero1α significantly inhibits calcium release from ER and cell death[2]. | ||||||||||||
| In Vivo | To evaluate the in vivo effect of WF-210 on the growth of malignant tumors, we examined the ability of WF-210 to suppress tumor growth in mouse Hep3B and MDA-MB-435 xenograft models. These two cell lines express procaspase-3 at relatively high levels. Tumors induced by xenografts of the liver cancer cell Hep3B are allowed to develop and grow to a size of 100 mm3, after which WF-210 (2.5 mg/kg) or PAC-1 (5.0 mg/kg) is given daily for two weeks by intravenous (i.v.) administration. As shown in both PAC-1 and WF-210 significantly inhibits the growth of Hep3B tumor xenografts[1]. | ||||||||||||
| Name | PAC-1 | ||||||||||||
| CAS | 315183-21-2 | ||||||||||||
| Formula | C23H28N4O2 | ||||||||||||
| Molar Mass | 392.49 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Wang F, et al. A novel small-molecule activator of procaspase-3 induces apoptosis in cancer cells and reduces tumor growth in human breast, liver and gallbladder cancer xenografts. Mol Oncol. 2014 Dec;8(8):1640-52. [2]. Seervi M, et al. ERO1α-dependent endoplasmic reticulum-mitochondrial calcium flux contributes to ER stress and mitochondrial permeabilization by procaspase-activating compound-1 (PAC-1). Cell Death Dis. 2013 Dec 19;4:e968. [3]. Putt KS, et al. Small-molecule activation of procaspase-3 to caspase-3 as a personalized anticancer strategy. Nat Chem Biol. 2006 Oct;2(10):543-50. |