PAC-1 是一种 procaspase-3 激活剂，诱导癌

PAC-1 is a procaspase-3 activator that induces apoptosis in cancer cells with an EC₅₀ of 2.08 μM.

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].

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].

392.49

C₂₃H₂₈N₄O₂

315183-21-2

半胱天冬酶原活化物1

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DMSO : 50 mg/mL (127.39 mM; Need ultrasonic)

H₂O : < 0.1 mg/mL (insoluble)

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• 1.

  请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline

  Solubility: ≥ 2.5 mg/mL (6.37 mM); Clear solution

• 2.

  请依序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline)

  Solubility: 2.5 mg/mL (6.37 mM); Suspended solution; Need ultrasonic

• 3.

  请依序添加每种溶剂： 10% DMSO 90% corn oil

  Solubility: ≥ 2.5 mg/mL (6.37 mM); Clear solution

• [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.