Leland Stanford Junior University

University of Mississippi

The Gillette Company

Bin Shen

Sanjiv Sam Gambhir

Jianghong Rao

Ashok Bakul Patel

Kenneth James Skrobis

Yongqing Ju

Frederick T Chin

Zhen Cheng

Matthew Robert Stone

Michelle Louise James

Christopher R McCurdy

Christophe Mesangeau

Benjamin Joseph Hackel

Sandip Biswal

Richard H Kimura

John Joseph Nisby

Jason Scott Slattery

Adam Shuhendler

Deepak Behera

Robert Teed

Jongho Jeon

Frederick Te-Ning Chin

Deju Ye

Jeffrey S Parker

A method for localizing and quantifying S1R role in nociceptive processing; for providing a guide to providing an analgesic therapy; of using an S1R selective ligand as a biomarker for pathphysiological study of memory deficits and cognitive disorders; or of detecting increased S1R density at the site of nerve injury arising from neuropathic pain comprising using as a probe at least one SR1 selective compound or radioligand of the general formula III', or IV&#x2032;: 

Highly selective sigma receptor ligands and radioligands as probes in nociceptive processing and the pathphysiological study of memory deficits and cognitive disorders

Provided is an activatable probe that undergoes intramolecular cyclization and subsequent aggregation in apoptotic tumor cells upon peptidase-initiated, and most advantageously caspase-3, activation. These caspase-sensitive nano-aggregation probes (C-SNAFs) are generally biocompatible, possess NIR spectral properties or may serve as PET or MRI imaging agents, and have a mechanism of target-mediated nanostructure self-assembly amenable to in vivo use. The probes encompass biocompatible condensation chemistry products that comprise D-cysteine and 2-cyano-6-hydroxyquinoline (CHQ) moieties linked to an amino-luciferin scaffold, and which can be activated by a two-step reaction requiring caspase-3/7-mediated cleavage of an aspartate-glutamate-valine-aspartate (L-DEVD) capping peptide and the free intracellular thiol-mediated reduction of the disulfide bond.

Caspase-triggered nano-aggregation probes and methods of use

Compounds having the general formula III', or IV&#x2032; wherein Rcan be a radical of an optionally substituted C-4 to C-7 N-containing heterocycle or a radical of an optionally substituted cyclic or acyclic tertiary amine or isoindoline-1,3-dione: Rcan each independently be any one or combinations of the following moieties, cyano, nitro, acyl, alkyl, amido, azido, isothiocyanate, isocyanate, optionally substituted anilino, halogens, ethers, sulfonamides, thioacyl, nitro, aromatic, heterocyclic, olefinic, acetylene, deuterium, or tritium; Y is S; Z can be either H, O, S, S&#x2014;R or NR where R groups can be either H, aryls, alkyls, or cycloalkyls; 'n' can be 1 to 5 carbons in length and stereoisomers, functional analogs, and pharmaceutically acceptable salts thereof and wherein the moiety bridging Rand N can be a substituted alkylene, optionally substituted alkenylene or optionally substituted alkynylene and where the alkylene group can include an inserted C-Ccycloalkyl group, aromatic, and heterocyclic group; and wherein X is C-Cradiohaloalkyl.

Highly selective sigma receptor radioligands

Disclosed are peptides comprising a molecular scaffold portion and a loop portion that binds to integrin &#x3b1;&#x3b2;. This integrin is expressed on pancreatic tumors, making the peptides useful as imaging agents, among other uses. The peptides showed single-digit nanomolar dissociation constants similar to antibodies used clinically for imaging and therapy. The peptides rapidly accumulated in &#x3b1;&#x3b2;-positive tumors, which led to excellent tumor-to-normal contrast. The peptides are specific for the targeted integrin &#x3b1;&#x3b2;receptors expressed on orthotopic pancreatic tumors and various xenografts used. Additionally, pharmacokinetic-stabilization strategies endowed knots with rapid renal clearance, which significantly reduced off-target dosing.

Cystine knot peptides that bind alpha-V-beta-6 integrin

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Mountain View, CA, United States of America

Bin Shen