ArticleJournal of the American Chemical Society2014
Dual small-molecule targeting of procaspase-3 dramatically enhances zymogen activation and anticancer activity.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Inhalable Mucoadhesive Redox-Triggered Nanotherapeutics for p53-Mediated Lung Cancer Therapy and Metastasis Suppression.Advanced healthcare materials · 2026Article
- Hypochlorous Acid-Gated Hydrolysis of a Phosphinate Ester Dye in Living Cells.Journal of the American Chemical Society · 2025Article
- PAC-1 Synergizes with Sunitinib to Enhance Cell Death in Pancreatic Neuroendocrine Tumors.ACS pharmacology & translational science · 2025Article
- Marine-derived EGFR inhibitors: novel compounds targeting breast cancer growth and drug resistance.Frontiers in pharmacology · 2024Article
- Regulation of Peptidase Activity beyond the Active Site in Human Health and Disease.International journal of molecular sciences · 2023Review
- The evolution of small molecule enzyme activators.RSC medicinal chemistry · 2023Review
- Phase I study of procaspase-activating compound-1 (PAC-1) in the treatment of advanced malignancies.British journal of cancer · 2023Article
- Cell-Permeant Bioadaptors for Cytosolic Delivery of Native Antibodies: A "Mix-and-Go" Approach.ACS central science · 2020Article
- Procaspase-3 Overexpression in Cancer: A Paradoxical Observation with Therapeutic Potential.ACS chemical biology · 2019Review
- Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials.Science translational medicine · 2019Article
- Diverse compounds from pleuromutilin lead to a thioredoxin inhibitor and inducer of ferroptosis.Nature chemistry · 2019Article
- Immunohistochemical Characterization of Procaspase-3 Overexpression as a Druggable Target With PAC-1, a Procaspase-3 Activator, in Canine and Human Brain Cancers.Frontiers in oncology · 2019Article
- Design and Synthesis of Bioisosteres of Acylhydrazones as Stable Inhibitors of the Aspartic Protease Endothiapepsin.ChemMedChem · 2018Article
- Article
- Rational Design of Selective Allosteric Inhibitors of PHGDH and Serine Synthesis with Anti-tumor Activity.Cell chemical biology · 2017Article
- Small-Molecule Procaspase-3 Activation Sensitizes Cancer to Treatment with Diverse Chemotherapeutics.ACS central science · 2016Article
- The Combination of Vemurafenib and Procaspase-3 Activation Is Synergistic in Mutant BRAF Melanomas.Molecular cancer therapeutics · 2016Article
- Molecular evidence of Zn chelation of the procaspase activating compound B-PAC-1 in B cell lymphoma.Oncotarget · 2016Article
- Derivatives of Procaspase-Activating Compound 1 (PAC-1) and their Anticancer Activities.Current medicinal chemistry · 2016Article
- A Small Molecule that Induces Intrinsic Pathway Apoptosis with Unparalleled Speed.Cell reports · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Combination anticancer therapy typically consists of drugs that target different biochemical pathways or those that act on different targets in the same pathway. Here we demonstrate a new concept in combination therapy, that of enzyme activation with two compounds that hit the same biological target, but through different mechanisms. Combinations of procaspase-3 activators PAC-1 and 1541B show considerable synergy in activating procaspase-3 in vitro, stimulate rapid and dramatic maturation of procaspase-3 in multiple cancer cell lines, and powerfully induce caspase-dependent apoptotic death to a degree well exceeding the additive effect. In addition, the combination of PAC-1 and 1541B effectively reduces tumor burden in a murine lymphoma model at dosages for which the compounds alone have minimal or no effect. These data suggest the potential of PAC-1/1541B combinations for the treatment of cancer and, more broadly, demonstrate that differentially acting enzyme activators can potently synergize to give a significantly heightened biological effect.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.