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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C23H28N4O2 |
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分子量 | 392.49 | CAS No. | 315183-21-2 | |
Solubility (25°C)* | 体外 | DMSO | 78 mg/mL (198.73 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <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. |
製品説明 | 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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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] |
特徴 | The first small molecule known to directly activate procaspase-3 to caspase-3. |
キナーゼアッセイ | In vitro procaspase-3 activation | |
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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. | ||
細胞アッセイ | 細胞株 | 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 |
濃度 | Dissolved in DMSO, final concentrations ~100 μM | |
反応時間 | 72 hours | |
実験の流れ | 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 | |
動物実験 | 動物モデル | 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 |
投薬量 | ~100 mg/kg | |
投与方法 | Pellet implantation subcutaneously or oral gavage |
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Data from [Data independently produced by , , Biol Med, 2015, 7(5).doi: 10.4172/0974-8369.1000259.]
Aedes aegypti Argonaute 2 controls arbovirus infection and host mortality [ Nat Commun, 2023, 14(1):5773] | PubMed: 37723154 |
Aedes aegypti Argonaute 2 controls arbovirus infection and host mortality [ Nat Commun, 2023, 14(1):5773] | PubMed: 37723154 |
Caspase 3 exhibits a yeast metacaspase proteostasis function that protects mitochondria from toxic TDP43 aggregates [ Microb Cell, 2023, 10(8):157-169] | PubMed: 37545643 |
PEBP balances apoptosis and autophagy in whitefly upon arbovirus infection [ Nat Commun, 2022, 13(1):846] | PubMed: 35149691 |
COL8A1 Promotes NSCLC Progression Through IFIT1/IFIT3-Mediated EGFR Activation [ Front Oncol, 2022, 12:707525] | PubMed: 35280763 |
ANP32E contributes to gastric cancer progression via NUF2 upregulation [ Mol Med Rep, 2022, 26(3)275] | PubMed: 35795988 |
Modulating environmental signals to reveal mechanisms and vulnerabilities of cancer persisters [ Sci Adv, 2022, 8(4):eabi7711] | PubMed: 35089788 |
Microbes exploit death-induced nutrient release by gut epithelial cells [ Nature, 2021, 10.1038/s41586-021-03785-9] | PubMed: 34349263 |
The Zebrafish Antiapoptotic Protein BIRC2 Promotes Edwardsiella piscicida Infection by Inhibiting Caspases and Accumulating p53 in a p53 Transcription-Dependent and -Independent Manner [ Front Immunol, 2021, 12:781680] | PubMed: 34887869 |
Cooperative application of transcriptomics and ceRNA hypothesis: LncRNA-107052630/miR-205a/G0S2 crosstalk is involved in ammonia-induced intestinal apoptotic injury in chicken. [ J Hazard Mater, 2020, 18;396:122605] | PubMed: 32334290 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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