PAC-1
First procaspase-activating compound (PAC-1) is a small-molecule activator of procaspase-3 that directly catalyzes the maturation of procaspase-3 to the active caspase-3 by inducing the cleavage of procaspase-3 in a time-dependent manner. As a result of the direct and immediate activation of procaspase-3, PAC-1 potently induces apoptosis in cancer cell lines. The PAC-1 induced apoptosis has been observed to be proportional to the concentrations of procaspase-3 inside the cells of primary colon cancer isolates. Study results have demonstrated that PAC-1 is able to induce cell death in both primary cancerous cells and adjacent normal tissues with 50% inhibition concentration IC50 values ranging from 0.003 to 1.41 μM and 5.02 to 9.98 μM respectively.
Reference
Putt KS, Chen GW, Pearson JM, Sandhorst JS, Hoagland MS, Kwon JT, Hwang SK, Jin H, Churchwell MI, Cho MH, Doerge DR, Helferich WG, Hergenrother PJ. Small-molecule activation of procaspase-3 to caspase-3 as a personalized anticancer strategy. Nat Chem Biol. 2006 Oct;2(10):543-50. Epub 2006 Aug 27.
- 1. Wenbo Huo, Jinghua Yu, et al. "Caspase-3 inhibitor inhibits enterovirus D68 production." J Microbiol 2020 Sep;58(9):812-820. PMID:32870487
- 2. Liu H, Kai L, et al. "LPS Inhibits Fatty Acid Absorption in Enterocytes through TNF-α Secreted by Macrophages." Cells. 2019 Dec 12;8(12). pii: E1626. PMID:31842409
- 3. Martin PK, Marchiando A, et al. "Autophagy proteins suppress protective type I interferon signalling in response to the murine gut microbiota." Nat Microbiol. 2018 Oct;3(10):1131-1141. PMID:30202015
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 392.49 |
| Cas No. | 315183-21-2 |
| Formula | C23H28N4O2 |
| Solubility | insoluble in H2O; ≥13.4 mg/mL in DMSO; ≥6.87 mg/mL in EtOH with ultrasonic |
| Chemical Name | 2-(4-benzylpiperazin-1-yl)-N'-[(Z)-(6-oxo-5-prop-2-enylcyclohexa-2,4-dien-1-ylidene)methyl]acetohydrazide |
| SDF | Download SDF |
| Canonical SMILES | C=CCC1=CC=CC(=CNNC(=O)CN2CCN(CC2)CC3=CC=CC=C3)C1=O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
Several cancer cell lines (leukemia, lymphoma, melanoma, neuroblastoma, breast cancer, lung cancer, adrenal cancer and renal cancer) |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months. |
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Reaction Conditions |
72 hrs |
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Applications |
PAC-1 induces cell death in a procaspase-3-dependant manner. PAC-1 is most potent against the lung cancer cell line NCI-H226, with an IC50 value of 0.35 μM. |
| Animal experiment [1]: | |
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Animal models |
Mice s.c. injected with NCI-H226 (lung cancer) cells |
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Dosage form |
0, 50 or 100 mg/kg; p.o.; q.d., for 21 days |
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Applications |
In mice s.c. injected with NCI-H226 (lung cancer) cells, PAC-1 significantly retarded tumor growth in a dose-dependent manner. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Putt KS, Chen GW, Pearson JM, Sandhorst JS, Hoagland MS, Kwon JT, Hwang SK, Jin H, Churchwell MI, Cho MH, Doerge DR, Helferich WG, Hergenrother PJ. Small-molecule activation of procaspase-3 to caspase-3 as a personalized anticancer strategy. Nat Chem Biol. 2006 Oct;2(10):543-50. Epub 2006 Aug 27. |
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| Procaspase-activating compound; activates procaspase-3 to produce caspase-3 (EC50 = 0.22 μM). Also activates procaspase-7 in a less efficient manner (EC50 = 4.5 μM). | ||||||
Quality Control & MSDS
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Chemical structure
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