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First-in-class pan caspase inhibitor developed for the treatment of liver disease.

Linton SD, Aja T, Armstrong RA, Bai X, Chen LS, Chen N, Ching B, Contreras P, Diaz JL, Fisher CD, Fritz LC, Gladstone P, Groessl T, Gu X, Herrmann J, Hirakawa BP, Hoglen NC, Jahangiri KG, Kalish VJ, Karanewsky DS, Kodandapani L, Krebs J, McQuiston J, Meduna SP, Nalley K, Robinson ED, Sayers RO, Sebring K, Spada AP, Ternansky RJ, Tomaselli KJ, Ullman BR, Valentino KL, Weeks S, Winn D, Wu JC, Yeo P, Zhang CZ.

J Med Chem. 2005 Nov 3;48(22):6779-82.


Structure-activity relationships within a series of caspase inhibitors. Part 2: Heterocyclic warheads.

Ullman BR, Aja T, Chen N, Diaz JL, Gu X, Herrmann J, Kalish VJ, Karanewsky DS, Kodandapani L, Krebs JJ, Linton SD, Meduna SP, Nalley K, Robinson ED, Roggo SP, Sayers RO, Schmitz A, Ternansky RJ, Tomaselli KJ, Wu JC.

Bioorg Med Chem Lett. 2005 Aug 1;15(15):3632-6.


An inhibitor of Bcl-2 family proteins induces regression of solid tumours.

Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, Bruncko M, Deckwerth TL, Dinges J, Hajduk PJ, Joseph MK, Kitada S, Korsmeyer SJ, Kunzer AR, Letai A, Li C, Mitten MJ, Nettesheim DG, Ng S, Nimmer PM, O'Connor JM, Oleksijew A, Petros AM, Reed JC, Shen W, Tahir SK, Thompson CB, Tomaselli KJ, Wang B, Wendt MD, Zhang H, Fesik SW, Rosenberg SH.

Nature. 2005 Jun 2;435(7042):677-81. Epub 2005 May 15.


Discovery of potent antagonists of the antiapoptotic protein XIAP for the treatment of cancer.

Oost TK, Sun C, Armstrong RC, Al-Assaad AS, Betz SF, Deckwerth TL, Ding H, Elmore SW, Meadows RP, Olejniczak ET, Oleksijew A, Oltersdorf T, Rosenberg SH, Shoemaker AR, Tomaselli KJ, Zou H, Fesik SW.

J Med Chem. 2004 Aug 26;47(18):4417-26.


Oxamyl dipeptide caspase inhibitors developed for the treatment of stroke.

Linton SD, Aja T, Allegrini PR, Deckwerth TL, Diaz JL, Hengerer B, Herrmann J, Jahangiri KG, Kallen J, Karanewsky DS, Meduna SP, Nalley K, Robinson ED, Roggo S, Rovelli G, Sauter A, Sayers RO, Schmitz A, Smidt R, Ternansky RJ, Tomaselli KJ, Ullman BR, Wiessner C, Wu JC.

Bioorg Med Chem Lett. 2004 May 17;14(10):2685-91.


Structure-activity relationships within a series of caspase inhibitors: effect of leaving group modifications.

Ullman BR, Aja T, Deckwerth TL, Diaz JL, Herrmann J, Kalish VJ, Karanewsky DS, Meduna SP, Nalley K, Robinson ED, Roggo SP, Sayers RO, Schmitz A, Ternansky RJ, Tomaselli KJ, Wu JC.

Bioorg Med Chem Lett. 2003 Oct 20;13(20):3623-6.


Improved resuscitation after cardiac arrest in rats expressing the baculovirus caspase inhibitor protein p35 in central neurons.

Vogel P, Putten Hv, Popp E, Krumnikl JJ, Teschendorf P, Galmbacher R, Kisielow M, Wiessner C, Schmitz A, Tomaselli KJ, Schmitz B, Martin E, Böttiger BW.

Anesthesiology. 2003 Jul;99(1):112-21.


Structural and functional analysis of caspase active sites.

Chéreau D, Kodandapani L, Tomaselli KJ, Spada AP, Wu JC.

Biochemistry. 2003 Apr 15;42(14):4151-60.


Regulation of the Apaf-1/caspase-9 apoptosome by caspase-3 and XIAP.

Zou H, Yang R, Hao J, Wang J, Sun C, Fesik SW, Wu JC, Tomaselli KJ, Armstrong RC.

J Biol Chem. 2003 Mar 7;278(10):8091-8. Epub 2002 Dec 27.


Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome.

Marsden VS, O'Connor L, O'Reilly LA, Silke J, Metcalf D, Ekert PG, Huang DC, Cecconi F, Kuida K, Tomaselli KJ, Roy S, Nicholson DW, Vaux DL, Bouillet P, Adams JM, Strasser A.

Nature. 2002 Oct 10;419(6907):634-7. Epub 2002 Sep 25.


Acyl dipeptides as reversible caspase inhibitors. Part 2: further optimization.

Linton SD, Karanewsky DS, Ternansky RJ, Chen N, Guo X, Jahangiri KG, Kalish VJ, Meduna SP, Robinson ED, Ullman BR, Wu JC, Pham B, Kodandapani L, Smidt R, Diaz JL, Fritz LC, von Krosigk U, Roggo S, Schmitz A, Tomaselli KJ.

Bioorg Med Chem Lett. 2002 Oct 21;12(20):2973-5.


Acyl dipeptides as reversible caspase inhibitors. Part 1: initial lead optimization.

Linton SD, Karanewsky DS, Ternansky RJ, Wu JC, Pham B, Kodandapani L, Smidt R, Diaz JL, Fritz LC, Tomaselli KJ.

Bioorg Med Chem Lett. 2002 Oct 21;12(20):2969-71.


Modulation of Apoptosis As a Therapeutic Strategy.

Tomaselli KJ.

ScientificWorldJournal. 2001 Oct 2;1:104. doi: 10.1100/tsw.2001.131. eCollection 2001. No abstract available.


Characterization of the caspase inhibitor IDN-1965 in a model of apoptosis-associated liver injury.

Hoglen NC, Hirakawa BP, Fisher CD, Weeks S, Srinivasan A, Wong AM, Valentino KL, Tomaselli KJ, Bai X, Karanewsky DS, Contreras PC.

J Pharmacol Exp Ther. 2001 May;297(2):811-8.


Heavy membrane-associated caspase 3: identification, isolation, and characterization.

Krebs JF, Srinivasan A, Wong AM, Tomaselli KJ, Fritz LC, Wu JC.

Biochemistry. 2000 Dec 26;39(51):16056-63.


Drug discovery opportunities from apoptosis research.

Reed JC, Tomaselli KJ.

Curr Opin Biotechnol. 2000 Dec;11(6):586-92. Review.


Dual role of caspase-11 in mediating activation of caspase-1 and caspase-3 under pathological conditions.

Kang SJ, Wang S, Hara H, Peterson EP, Namura S, Amin-Hanjani S, Huang Z, Srinivasan A, Tomaselli KJ, Thornberry NA, Moskowitz MA, Yuan J.

J Cell Biol. 2000 May 1;149(3):613-22.


DNA damage and activated caspase-3 expression in neurons and astrocytes: evidence for apoptosis in frontotemporal dementia.

Su JH, Nichol KE, Sitch T, Sheu P, Chubb C, Miller BL, Tomaselli KJ, Kim RC, Cotman CW.

Exp Neurol. 2000 May;163(1):9-19.


The three-dimensional structure of caspase-8: an initiator enzyme in apoptosis.

Blanchard H, Kodandapani L, Mittl PR, Marco SD, Krebs JF, Wu JC, Tomaselli KJ, Grütter MG.

Structure. 1999 Sep 15;7(9):1125-33.


Activation of caspase-3 in developmental models of programmed cell death in neurons of the substantia nigra.

Jeon BS, Kholodilov NG, Oo TF, Kim SY, Tomaselli KJ, Srinivasan A, Stefanis L, Burke RE.

J Neurochem. 1999 Jul;73(1):322-33.


ATP-dependent steps in apoptotic signal transduction.

Eguchi Y, Srinivasan A, Tomaselli KJ, Shimizu S, Tsujimoto Y.

Cancer Res. 1999 May 1;59(9):2174-81.


Activation of membrane-associated procaspase-3 is regulated by Bcl-2.

Krebs JF, Armstrong RC, Srinivasan A, Aja T, Wong AM, Aboy A, Sayers R, Pham B, Vu T, Hoang K, Karanewsky DS, Leist C, Schmitz A, Wu JC, Tomaselli KJ, Fritz LC.

J Cell Biol. 1999 Mar 8;144(5):915-26.


In situ immunodetection of activated caspase-3 in apoptotic neurons in the developing nervous system.

Srinivasan A, Roth KA, Sayers RO, Shindler KS, Wong AM, Fritz LC, Tomaselli KJ.

Cell Death Differ. 1998 Dec;5(12):1004-16.


Conformationally constrained inhibitors of caspase-1 (interleukin-1 beta converting enzyme) and of the human CED-3 homologue caspase-3 (CPP32, apopain).

Karanewsky DS, Bai X, Linton SD, Krebs JF, Wu J, Pham B, Tomaselli KJ.

Bioorg Med Chem Lett. 1998 Oct 6;8(19):2757-62.


Interaction of the baculovirus anti-apoptotic protein p35 with caspases. Specificity, kinetics, and characterization of the caspase/p35 complex.

Zhou Q, Krebs JF, Snipas SJ, Price A, Alnemri ES, Tomaselli KJ, Salvesen GS.

Biochemistry. 1998 Jul 28;37(30):10757-65.


Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia.

Namura S, Zhu J, Fink K, Endres M, Srinivasan A, Tomaselli KJ, Yuan J, Moskowitz MA.

J Neurosci. 1998 May 15;18(10):3659-68.


Two CD95 (APO-1/Fas) signaling pathways.

Scaffidi C, Fulda S, Srinivasan A, Friesen C, Li F, Tomaselli KJ, Debatin KM, Krammer PH, Peter ME.

EMBO J. 1998 Mar 16;17(6):1675-87.


Bcl-xL functions downstream of caspase-8 to inhibit Fas- and tumor necrosis factor receptor 1-induced apoptosis of MCF7 breast carcinoma cells.

Srinivasan A, Li F, Wong A, Kodandapani L, Smidt R Jr, Krebs JF, Fritz LC, Wu JC, Tomaselli KJ.

J Biol Chem. 1998 Feb 20;273(8):4523-9.


Human IAP-like protein regulates programmed cell death downstream of Bcl-xL and cytochrome c.

Duckett CS, Li F, Wang Y, Tomaselli KJ, Thompson CB, Armstrong RC.

Mol Cell Biol. 1998 Jan;18(1):608-15.


Cell-specific induction of apoptosis by microinjection of cytochrome c. Bcl-xL has activity independent of cytochrome c release.

Li F, Srinivasan A, Wang Y, Armstrong RC, Tomaselli KJ, Fritz LC.

J Biol Chem. 1997 Nov 28;272(48):30299-305.


FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis.

Srinivasula SM, Ahmad M, Ottilie S, Bullrich F, Banks S, Wang Y, Fernandes-Alnemri T, Croce CM, Litwack G, Tomaselli KJ, Armstrong RC, Alnemri ES.

J Biol Chem. 1997 Jul 25;272(30):18542-5.


Identification of the MDM2 oncoprotein as a substrate for CPP32-like apoptotic proteases.

Erhardt P, Tomaselli KJ, Cooper GM.

J Biol Chem. 1997 Jun 13;272(24):15049-52.


Structure of recombinant human CPP32 in complex with the tetrapeptide acetyl-Asp-Val-Ala-Asp fluoromethyl ketone.

Mittl PR, Di Marco S, Krebs JF, Bai X, Karanewsky DS, Priestle JP, Tomaselli KJ, Grütter MG.

J Biol Chem. 1997 Mar 7;272(10):6539-47.


Death effector domain-containing herpesvirus and poxvirus proteins inhibit both Fas- and TNFR1-induced apoptosis.

Bertin J, Armstrong RC, Ottilie S, Martin DA, Wang Y, Banks S, Wang GH, Senkevich TG, Alnemri ES, Moss B, Lenardo MJ, Tomaselli KJ, Cohen JI.

Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1172-6.


Activation of the CED3/ICE-related protease CPP32 in cerebellar granule neurons undergoing apoptosis but not necrosis.

Armstrong RC, Aja TJ, Hoang KD, Gaur S, Bai X, Alnemri ES, Litwack G, Karanewsky DS, Fritz LC, Tomaselli KJ.

J Neurosci. 1997 Jan 15;17(2):553-62.


The Ced-3/interleukin 1beta converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2alpha are substrates for the apoptotic mediator CPP32.

Srinivasula SM, Fernandes-Alnemri T, Zangrilli J, Robertson N, Armstrong RC, Wang L, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES.

J Biol Chem. 1996 Oct 25;271(43):27099-106.


Apoptotic suppression by baculovirus P35 involves cleavage by and inhibition of a virus-induced CED-3/ICE-like protease.

Bertin J, Mendrysa SM, LaCount DJ, Gaur S, Krebs JF, Armstrong RC, Tomaselli KJ, Friesen PD.

J Virol. 1996 Sep;70(9):6251-9.


In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains.

Fernandes-Alnemri T, Armstrong RC, Krebs J, Srinivasula SM, Wang L, Bullrich F, Fritz LC, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES.

Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7464-9.


Fas-induced activation of the cell death-related protease CPP32 Is inhibited by Bcl-2 and by ICE family protease inhibitors.

Armstrong RC, Aja T, Xiang J, Gaur S, Krebs JF, Hoang K, Bai X, Korsmeyer SJ, Karanewsky DS, Fritz LC, Tomaselli KJ.

J Biol Chem. 1996 Jul 12;271(28):16850-5.


Mch3, a novel human apoptotic cysteine protease highly related to CPP32.

Fernandes-Alnemri T, Takahashi A, Armstrong R, Krebs J, Fritz L, Tomaselli KJ, Wang L, Yu Z, Croce CM, Salveson G, et al.

Cancer Res. 1995 Dec 15;55(24):6045-52.


Peptide inhibitors of the ICE protease family arrest programmed cell death of motoneurons in vivo and in vitro.

Milligan CE, Prevette D, Yaginuma H, Homma S, Cardwell C, Fritz LC, Tomaselli KJ, Oppenheim RW, Schwartz LM.

Neuron. 1995 Aug;15(2):385-93.


Secondary structure of amyloid beta peptide correlates with neurotoxic activity in vitro.

Simmons LK, May PC, Tomaselli KJ, Rydel RE, Fuson KS, Brigham EF, Wright S, Lieberburg I, Becker GW, Brems DN, et al.

Mol Pharmacol. 1994 Mar;45(3):373-9.


Expression of beta 1 integrins in sensory neurons of the dorsal root ganglion and their functions in neurite outgrowth on two laminin isoforms.

Tomaselli KJ, Doherty P, Emmett CJ, Damsky CH, Walsh FS, Reichardt LF.

J Neurosci. 1993 Nov;13(11):4880-8.


2001 interactions? An extracellular space odyssey.

Tomaselli KJ, Neugebauer KM.

Curr Opin Neurobiol. 1991 Oct;1(3):364-9. Review. No abstract available.


Extracellular matrix molecules and their receptors: functions in neural development.

Reichardt LF, Tomaselli KJ.

Annu Rev Neurosci. 1991;14:531-70. Review. No abstract available.


A neuronal cell line (PC12) expresses two beta 1-class integrins-alpha 1 beta 1 and alpha 3 beta 1-that recognize different neurite outgrowth-promoting domains in laminin.

Tomaselli KJ, Hall DE, Flier LA, Gehlsen KR, Turner DC, Carbonetto S, Reichardt LF.

Neuron. 1990 Nov;5(5):651-62.


Integrins and cell adhesion molecules: neuronal receptors that regulate axon growth on extracellular matrices and cell surfaces.

Reichardt LF, Bixby JL, Hall DE, Ignatius MJ, Neugebauer KM, Tomaselli KJ.

Dev Neurosci. 1989;11(4-5):332-47. Review. No abstract available.


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