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Dual small-molecule targeting of procaspase-3 dramatically enhances zymogen activation and anticancer activity.

Botham RC, Fan TM, Im I, Borst LB, Dirikolu L, Hergenrother PJ.

J Am Chem Soc. 2014 Jan 29;136(4):1312-9. doi: 10.1021/ja4124303. Epub 2014 Jan 16.


Small-molecule activation of procaspase-3 to caspase-3 as a personalized anticancer strategy.

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.

Nat Chem Biol. 2006 Oct;2(10):543-50. Epub 2006 Aug 27.


Procaspase-3 activation as an anti-cancer strategy: structure-activity relationship of procaspase-activating compound 1 (PAC-1) and its cellular co-localization with caspase-3.

Peterson QP, Hsu DC, Goode DR, Novotny CJ, Totten RK, Hergenrother PJ.

J Med Chem. 2009 Sep 24;52(18):5721-31. doi: 10.1021/jm900722z.


Parallel synthesis and biological evaluation of 837 analogues of procaspase-activating compound 1 (PAC-1).

Hsu DC, Roth HS, West DC, Botham RC, Novotny CJ, Schmid SC, Hergenrother PJ.

ACS Comb Sci. 2012 Jan 9;14(1):44-50. doi: 10.1021/co2001372. Epub 2011 Oct 28.


Pharmacokinetics and derivation of an anticancer dosing regimen for PAC-1, a preferential small molecule activator of procaspase-3, in healthy dogs.

Lucas PW, Schmit JM, Peterson QP, West DC, Hsu DC, Novotny CJ, Dirikolu L, Churchwell MI, Doerge DR, Garrett LD, Hergenrother PJ, Fan TM.

Invest New Drugs. 2011 Oct;29(5):901-11. doi: 10.1007/s10637-010-9445-z. Epub 2010 May 25.


Discovery and canine preclinical assessment of a nontoxic procaspase-3-activating compound.

Peterson QP, Hsu DC, Novotny CJ, West DC, Kim D, Schmit JM, Dirikolu L, Hergenrother PJ, Fan TM.

Cancer Res. 2010 Sep 15;70(18):7232-41. doi: 10.1158/0008-5472.CAN-10-0766. Epub 2010 Sep 7.


Differential effects of procaspase-3 activating compounds in the induction of cancer cell death.

West DC, Qin Y, Peterson QP, Thomas DL, Palchaudhuri R, Morrison KC, Lucas PW, Palmer AE, Fan TM, Hergenrother PJ.

Mol Pharm. 2012 May 7;9(5):1425-34. doi: 10.1021/mp200673n. Epub 2012 Apr 27.


Procaspase-activating compound 1 induces a caspase-3-dependent cell death in cerebellar granule neurons.

Aziz G, Akselsen ØW, Hansen TV, Paulsen RE.

Toxicol Appl Pharmacol. 2010 Sep 15;247(3):238-42. doi: 10.1016/j.taap.2010.07.002. Epub 2010 Jul 16.


Cell death induced by novel procaspase-3 activators can be reduced by growth factors.

Boldingh Debernard KA, Aziz G, Gjesvik AT, Paulsen RE.

Biochem Biophys Res Commun. 2011 Sep 23;413(2):364-9. doi: 10.1016/j.bbrc.2011.08.107. Epub 2011 Aug 27.


Potential small-molecule activators of caspase-7 identified using yeast-based caspase-3 and -7 screening assays.

Pereira C, Lopes-Rodrigues V, Coutinho I, Neves MP, Lima RT, Pinto M, Cidade H, Vasconcelos MH, Saraiva L.

Eur J Pharm Sci. 2014 Apr 11;54:8-16. doi: 10.1016/j.ejps.2013.12.017. Epub 2014 Jan 4.


Removal of Metabolic Liabilities Enables Development of Derivatives of Procaspase-Activating Compound 1 (PAC-1) with Improved Pharmacokinetics.

Roth HS, Botham RC, Schmid SC, Fan TM, Dirikolu L, Hergenrother PJ.

J Med Chem. 2015 May 14;58(9):4046-65. doi: 10.1021/acs.jmedchem.5b00413. Epub 2015 Apr 20.


PAC-1 activates procaspase-3 in vitro through relief of zinc-mediated inhibition.

Peterson QP, Goode DR, West DC, Ramsey KN, Lee JJ, Hergenrother PJ.

J Mol Biol. 2009 Apr 24;388(1):144-58. doi: 10.1016/j.jmb.2009.03.003. Epub 2009 Mar 10.


A novel small-molecule activator of procaspase-3 induces apoptosis in cancer cells and reduces tumor growth in human breast, liver and gallbladder cancer xenografts.

Wang F, Wang L, Zhao Y, Li Y, Ping G, Xiao S, Chen K, Zhu W, Gong P, Yang J, Wu C.

Mol Oncol. 2014 Dec;8(8):1640-52. doi: 10.1016/j.molonc.2014.06.015. Epub 2014 Jul 3.


ERO1α-dependent endoplasmic reticulum-mitochondrial calcium flux contributes to ER stress and mitochondrial permeabilization by procaspase-activating compound-1 (PAC-1).

Seervi M, Sobhan PK, Joseph J, Ann Mathew K, Santhoshkumar TR.

Cell Death Dis. 2013 Dec 19;4:e968. doi: 10.1038/cddis.2013.502.


Synthesis and initial in vitro biological evaluation of two new zinc-chelating compounds: comparison with TPEN and PAC-1.

Strand OA, Aziz G, Ali SF, Paulsen RE, Hansen TV, Rongved P.

Bioorg Med Chem. 2013 Sep 1;21(17):5175-81. doi: 10.1016/j.bmc.2013.06.037. Epub 2013 Jun 26.


Essential requirement of cytochrome c release for caspase activation by procaspase-activating compound defined by cellular models.

Seervi M, Joseph J, Sobhan PK, Bhavya BC, Santhoshkumar TR.

Cell Death Dis. 2011 Sep 8;2:e207. doi: 10.1038/cddis.2011.90.


Pyrrolidinium fullerene induces apoptosis by activation of procaspase-9 via suppression of Akt in primary effusion lymphoma.

Watanabe T, Nakamura S, Ono T, Ui S, Yagi S, Kagawa H, Watanabe H, Ohe T, Mashino T, Fujimuro M.

Biochem Biophys Res Commun. 2014 Aug 15;451(1):93-100. doi: 10.1016/j.bbrc.2014.07.068. Epub 2014 Jul 22.


Cytochalasin D, LY294002 and olomoucine synergize in promoting death of melanoma cells through activation of caspase-3 and apoptosis.

Małecki JM, Bentke A, Ostrowska B, Laidler P.

Melanoma Res. 2010 Feb;20(1):52-8. doi: 10.1097/CMR.0b013e328332f1e6.


Palladacycle (BPC) antitumour activity against resistant and metastatic cell lines: the relationship with cytosolic calcium mobilisation and cathepsin B activity.

Bechara A, Barbosa CM, Paredes-Gamero EJ, Garcia DM, Silva LS, Matsuo AL, Nascimento FD, Rodrigues EG, Caires AC, Smaili SS, Bincoletto C.

Eur J Med Chem. 2014 May 22;79:24-33. doi: 10.1016/j.ejmech.2014.03.073. Epub 2014 Mar 28.

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