Cancer Drug Candidate Leads to Proteomics Method

Scientists at Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical have devised an affinity capture-based proteomics technique that could be used to identify and map dysregulated protein pathways in a number of different cancers.

The technique, which was detailed in a paper published Nature Chemical Biology, relies on the inhibitor PU-H71 – a small molecule that selectively binds tumor-enriched Hsp90 proteins, enabling pulldown of Hsp90-bound oncogenic client proteins. According to MSK researcher Gabriela Chiosis ― one of the developers of the method ― measurement of these captured proteins combined with bioinformatic analysis could provide a better understanding of tumor biology.

Recommended Readings: Barry S. Coller M.D. Monday Sept 26 2011

Monday Lectures

Combing Structure-Based Design and Mass Screening to Probe

 Ligand Binding to Integrin Receptors

Barry S. Coller  M.D.

Vice President for Medical Affairs and Physician-in-Chief

Laboratory of Blood and Vascular Biology

September 26, 2011,  Caspary Auditorium,  4 p.m.

Recommended Readings

Litvinov RI; Barsegov V; Schissler AJ; Fisher AR; Bennett JS; Weisel JW; Shuman H.  2011.  Dissociation of bimolecular αIIβ3-fibrinogen complex under a constant tensile force.   Biophysical Journal.  100(1):165-73.

Lord MS; Cheng B; McCarthy SJ; et al.  2011.  The modulation of platelet adhesion and activation by chitosan through plasma and extracellular matrix proteins.  Biomaterials. 32(28):6655-6662  (Request from Markus Library)

Blue R; Li JH; Steinberg J; et al.  2010.  Effects of limiting extension at the alpha IIb Genu on ligand binding to integrin alpha IIb beta 2.  Journal of Biological Chemistry.  285(23):17604-17613.

Sheldrake HM; Patterson LH.  2009.  Function and antagonism of beta(3) integrins in the development of cancer therapyCurrent Cancer Drug Targets. 9(4):519-540.  (Request from Markus Library)

Basani RB; Zhu H: Thornton MA: et al.  2009.  Species differences in small molecule binding to alpha IIb beta 3 are the result of sequence difference in 2 loops of the alpha IIb beta propeller.   Blood.  113(4):902-910.

Blue R; Kowalska MA; Hirsch J; et al.  2009.  Structural and therapeutic insights from the species specificity and in vivo antithrombotic activity of a novel alpha IIb beta 3 antagonist. Blood  114(1):195-201

Blue R; Murcia M; Karan C; et al.  2008.  Application of high-throughput screening to identify a novel alpha IIb-specific small-molecule inhibitor of alpha IIb 3-mediated platelet interaction with fibrinogen.  Blood.  111(3):1248-1256.

Hynes, RO.  2002.  Integrins: bidirectional, allosteric signaling machinesCell. 110(6):673-687.

Recommended Readings: Dennis W. Wolan, Ph.D. Jan 25, 2010

Monday Lecture Series

Directed Small Molecule Activation of Apoptotic Procaspases

Dennis W. Wolan, Ph.D.,

Post Doctoral Fellow, Department of Pharmaceutical Chemistry

University of California, San Francisco

January 25, 2010

Welch Hall,  Level Two

4:00p.m.-5:00 p.m

Recommended Articles:

Wolan DW, Zorn JA, Gray DC, et al.  2009.  Small-Molecule Activators of a Proenzyme SCIENCE 326( 5954): 853-858

Eisenstein M.  2010.  Caught in action. NATURE METHODS 7(1): 12-12

Chereau D, Zou H, Spada AP, et al.  2005.  A nucleotide binding site in caspase-9 regulates apoptosome activation.    BIOCHEMISTRY 44(13): 4971-4976

Wu JM, Gorman A, Zhou XH, et al.  2002.  Involvement of caspase-3 in photoreceptor cell apoptosis induced by in vivo blue light exposure. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 43(10): 3349-3354

Henzing AJ, Dodson H, Reid JM, et al.   2006.  Synthesis of novel caspase inhibitors for characterization of the active caspase proteome in vitro and in vivo .    JOURNAL OF MEDICINAL CHEMISTRY 49(26):7636-7645

Denault JB;  Drag M.;  Salvesen GS;  Alves J;  Heidt AB; Deveraux Q ; Harris JL .  2007.  Small molecules not direct activators of caspases. NATURE CHEMICAL BIOLOGY 3(9): 519-519

BOATRIGHT KM; Salveson GS.  2003.  Mechanisms of caspase activation. CURRENT OPINION IN CELL BIOLOGY 15: 725

BLANC C.  2000.  Caspase-3 is essential for procaspase-9 processing and cisplatin-induced apoptosis of MCF-7 breast cancer cells. CANCER RESEARCH 60 : 4386-4390