Antibodies
PAC-1
- 貨號 Cat. No.
- S2738
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
PAC-1
Catalog No.S2738
PAC-1 is a potent procaspase-3 activator with EC50 of 0.22 μM and the first small molecule known to directly activate procaspase-3 to caspase-3.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | PAC-1 is a potent procaspase-3 activator with EC50 of 0.22 μM and the first small molecule known to directly activate procaspase-3 to caspase-3. | |||||
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| Targets | Procaspase-3 | |||||
| IC50 | 0.22 μM [1] | |||||
| In vitro | PAC-1 activates procaspase-7 in a less efficient manner with EC50 of 4.5 μM. Elevated caspase 3 level in cancer cell lines allows PAC-1 to selectively induce apoptosis in a manner proportional to procaspase-3 concentration with IC50 of 0.35 μM for NCI-H226 cells to ~3.5 μM for UACC-62 cells. PAC-1 induces apoptosis in the primary cancerous cells with IC50 values of 3 nM to 1.41 μM, more potently than in the adjacent noncancerous cells with IC50 of 5.02 μM to 9.98 μM, which is also directly related to the distinct procaspase-3 concentration. [1] PAC-1 activates procaspase-3 by chelating zinc ions, thus relieving the zinc-mediated inhibition and allowing procaspase-3 to auto-activate itself to caspase-3. [2] PAC-1 is capable to induce cell death in Bax/Bak double-knockout cells and Bcl-2 and Bcl-xL-overexpressing cells with the same efficacy as its wild-type counterpart in a delayed manner. PAC-1 induces cytochrome c release in a caspase-3 independent manner, which subsequently triggers downstream caspase-3 activation and cell death. PAC-1 can not induce cell death and caspase-3 activation in Apaf-1 knockout cells, suggesting that apoptosome formation is essential for caspase-3 activation by PAC-1-mediated cell death. [3] | |||||
| In vivo | Administration of PAC-1 at 5 mg with low and steady releasing significantly inhibits the growth of ACHN renal cancer xenograft in mice. Oral administration of PAC-1 (50 or 100 mg/kg) significantly retards tumor growth of NCI-H226 lung cancer xenograft in a dose-dependent manner, and markedly prevents the cancer cells from infiltrating the lung tissue. The in vivo anti-tumor effect of PAC-1 is ascribed to procaspase-3 activation and subsequently apoptosis induction consistent with the activity in vitro. [1] | |||||
| Features | The first small molecule known to directly activate procaspase-3 to caspase-3. | |||||
Protocol(Only for Reference)
Kinase Assay: [1]
| 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. |
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Cell Assay: [1]
| Cell lines | U-937, HL-60, CRL-1872, ACHN, NCI-H226, Hs888Lu, Hs578Bst, MCF-10A, SK-MEL-5, BT-20, MDA-MB-231, UACC-62, SK-N-SH, B16-F10 , Hs 578t, and PC-12 |
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| Concentrations | Dissolved in DMSO, final concentrations ~100 μM |
| Incubation Time | 72 hours |
| Method | 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 |
Animal Study: [1]
| Animal Models | Ovariectomized female athymic BALB/c (nude, nu/nu) mice injected subcutaneously with ACHN cells, male athymic BALB/c nude mice injected subcutaneously with NCI-H226 cells, and male athymic BALB/c–/– mice injected intravenously with NCI-H226 cells |
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| Dosages | ~100 mg/kg |
| Administration | Pellet implantation subcutaneously or oral gavage |
| Solubility | 30% PEG400/0.5% Tween80/5% propylene glycol, 30 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT00106587 | Completed | Coronary Restenosis | UniversityHospital,Saarland | 2003-12 | Phase 1|Phase 2 |
| NCT00075686 | Completed | Pancreatic Cancer | SouthwestOncologyGroup|NationalCancerInstitute(NCI)|CancerandLeukemiaGroupB|NCICClinicalTrialsGroup | 2004-01 | Phase 3 |
| NCT00944996 | Completed | Major Depression | TiratCarmelMentalHealthCenter|UniversityofMichigan|ArielUniversityCenterofSamaria|TheNazarethHospital,Israel | 2009-06 | |
| NCT01454778 | Recruiting | Peripheral Vascular Disease | SanfordHealth|PatrickKelly | 2011-04 | |
| NCT01865136 | Recruiting | Pregnancy | KarolinskaInstitutet|KenyaMedicalResearchInstitute|UniversityofNairobi | 2013-05 | Phase 4 |
Chemical Information
| Molecular Weight (MW) | 392.49 |
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| Formula | C23H28N4O2 |
| CAS No. | 315183-21-2 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 78 mg/mL (198 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | 16 mg/mL (40 mM) | ||
| In vivo | 30% PEG400/0.5% Tween80/5% propylene glycol, | 30 mg/mL | |
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| Chemical Name | (E)-N’-(3-allyl-2-hydroxybenzylidene)-2-(4-benzylpiperazin-1-yl)acetohydrazide |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
|---|---|---|---|---|
| Mass(mg) | 0.39249 | 3.9249 | 7.8498 | 11.7747 |
