315183-21-2 Usage
Description
PAC-1, also known as procaspase-activating compound, is a potent activator of procaspase-3 with an EC50 of 0.22 μM. It is a chemical compound that directly activates procaspase-3, leading to the production of caspase-3. PAC-1 is characterized by its ability to induce apoptosis in various cancer cell lines and sensitize cancer cells to various chemotherapeutic agents.
Uses
Used in Cancer Treatment:
PAC-1 is used as a procaspase-3 activator for inducing apoptosis in a variety of cancer cell lines. Its mechanism of activation involves sequestering inhibitory zinc ions, allowing procaspase-3 to autoactivate. This process leads to the initiation of apoptosis, which is the programmed cell death that can help in the treatment of cancer.
Used in Enhancing Chemotherapy Efficacy:
PAC-1 is used as a sensitizer for cancer cells to various chemotherapeutic agents. By sensitizing cancer cells, PAC-1 can enhance the effectiveness of chemotherapy treatments, making them more efficient in targeting and eliminating cancer cells.
Used in Pharmaceutical Research:
PAC-1 is used as a research tool in the development of new cancer treatments and therapies. Its ability to activate procaspase-3 and induce apoptosis makes it a valuable compound for studying the mechanisms of cell death and the potential for new therapeutic interventions in cancer treatment.
Biological Activity
Procaspase-activating compound; activates procaspase-3 to produce caspase-3 (EC 50 = 0.22 μ M). Also activates procaspase-7 in a less efficient manner (EC 50 = 4.5 μ M). Pro-apoptotic; induces apoptosis in both cancerous and non-cancerous cells dependent on procaspase-3 concentration (IC 50 values are 0.003-1.41 and 5.02-9.98 μ M respectively).
References
1) Putt et al. (2006), Small-molecule activation of procaspase-3 to caspase-3 as a personalized anticancer strategy; Nat. Chem. Biol., 2 543
2) Peterson et al. (2009), PAC-1 activates procaspase-3 in vitro through relief of zinc-mediated inhibition; J. Mol. Biol., 388 144
3) Bolham et al. (2016), Small-Molecule Procaspase-3 Activation Sensitizes Cancer to Treatment with diverse Chemotherapeutics; ACS Cent. Sci., 2 545
Check Digit Verification of cas no
The CAS Registry Mumber 315183-21-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 3,1,5,1,8 and 3 respectively; the second part has 2 digits, 2 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 315183-21:
(8*3)+(7*1)+(6*5)+(5*1)+(4*8)+(3*3)+(2*2)+(1*1)=112
112 % 10 = 2
So 315183-21-2 is a valid CAS Registry Number.
InChI:InChI=1/C23H28N4O2/c1-2-7-20-10-6-11-21(23(20)29)16-24-25-22(28)18-27-14-12-26(13-15-27)17-19-8-4-3-5-9-19/h2-6,8-11,16,29H,1,7,12-15,17-18H2,(H,25,28)/b24-16+
315183-21-2Relevant articles and documents
Removal of metabolic liabilities enables development of derivatives of procaspase-activating compound 1 (PAC-1) with improved pharmacokinetics
Roth, Howard S.,Botham, Rachel C.,Schmid, Steven C.,Fan, Timothy M.,Dirikolu, Levent,Hergenrother, Paul J.
, p. 4046 - 4065 (2015/05/27)
Procaspase-activating compound 1 (PAC-1) is an o-hydroxy-N-acylhydrazone that induces apoptosis in cancer cells by chelation of labile inhibitory zinc from procaspase-3. PAC-1 has been assessed in a wide variety of cell culture experiments and in vivo models of cancer, with promising results, and a phase 1 clinical trial in cancer patients has been initiated (NCT02355535). For certain applications, however, the in vivo half-life of PAC-1 could be limiting. Thus, with the goal of developing a compound with enhanced metabolic stability, a series of PAC-1 analogues were designed containing modifications that systematically block sites of metabolic vulnerability. Evaluation of the library of compounds identified four potentially superior candidates with comparable anticancer activity in cell culture, enhanced metabolic stability in liver microsomes, and improved tolerability in mice. In head-to-head experiments with PAC-1, pharmacokinetic evaluation in mice demonstrated extended elimination half-lives and greater area under the curve values for each of the four compounds, suggesting them as promising candidates for further development.
DESIGN, SYNTHESIS AND EVALUATION OF PROCASPASE ACTIVATING COMPOUNDS AS PERSONALIZED ANTI-CANCER DRUGS
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Page/Page column 31, (2010/08/18)
Compositions and methods are disclosed in embodiments relating to induction of cell death such as in cancer cells. Compounds and related methods for synthesis and use thereof, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds are disclosed that have lower neurotoxicity effects than other compounds.