DR. WILLIAM GABRIEL HAWKINS, MD
Radiology at Parkview Pl, Saint Louis, MO

8143222, Mar 27, 2012

Oct 22, 2008

12/255947

Jonathan E. McDunn - University City MO, US
William G. Hawkins - Olivette MO, US
Robert H. Mach - Eureka MO, US
Richard A. Hotchkiss - Chesterfield MO, US

Washington University - Saint Louis MO

A61K 38/02, A61K 38/16, C07K 2/00, C07K 14/00

514 189, 514 193, 514 213, 514 214, 530324, 530326, 530345, 530402

Pharmaceutical compounds, pharmaceutical compositions and methods of treatment are disclosed, wherein a compound comprises a targeting moiety which, in free form, binds a cell receptor with a dissociation constant Kof less than about 10M, and a pharmaceutically active moiety, wherein the targeting moiety is other than an oligopeptide, a polypeptide, a peptidomimetic, a protein or a protein domain, and wherein the targeting moiety and the pharmaceutically active moiety are covalently attached. In some aspects, the targeting moiety binds a sigma-2 receptor with high affinity and high specificity, and the pharmaceutically active moiety is a pro-apoptotic peptide moiety. Methods of cancer treatment are disclosed comprising administering a disclosed pharmaceutical compound to a subject in need of thereof. The treatments selectively induce apoptosis in cancer cells. These methods can further comprise co-administration of radiation therapy and/or an additional chemotherapeutic agent.

7612085, Nov 3, 2009

Jul 11, 2007

11/776533

Robert H. Mach - Eureka MO, US
Zhude Tu - Eureka MO, US
Wenhua Chu - St. Louis MO, US
Suwanna Vangveravong - Ballwin MO, US
Richard Hotchkiss - Chesterfield MO, US
William Hawkins - Olivette MO, US
Rebecca Aft - Chesterfield MO, US

Washington University - St. Louis MO

A01N 43/42, A61K 31/44, C07D 221/02

514299, 546112, 546183

A series of N-substituted 9-azabicyclo[3. 3. 1]nonan-3α-yl phenylcarbamate analogs are disclosed, as well as methods of their preparation. Their affinities for sigma (σ1 and σ2) receptors are described. Two new compounds, N-(9-(4-aminobutyl)-9-azabicyclo[3. 3. 1]nonan-3α-yl)-N′-(2-methoxy-5-methylphenyl)carbamate and N-(9-(6-aminohexyl)-9-azabicyclo[3. 3. 1]nonan-3α-yl)-N′-(2-methoxy-5-methylphenyl)carbamate, are shown to have a high affinity and selectivity for σ2 versus σ1 receptors. Among the disclosed compounds are biotinylated and fluorescent analogs. These compounds can serve as probes to the σ2 receptor. In addition, some disclosed compounds can induce apoptotic cell death by both caspase-dependent and caspase-independent mechanisms, and are effective for treatment of tumors. The compounds can be used as chemotherapeutics or chemosensitizers in the treatment of a wide variety of solid tumors.

8168650, May 1, 2012

Aug 19, 2009

12/543647

Robert H. Mach - Eureka MO, US
Richard Hotchkiss - Chesterfield MO, US
William Hawkins - Olivette MO, US
Rebecca Aft - Chesterfield MO, US
Zhude Tu - Eureka MO, US

Washington University - Saint Louis MO

A01N 43/42, A61K 31/44

514299

A series of N-substituted 9-azabicyclo[3. 3. 1]nonan-3α-yl phenylcarbamate analogs are disclosed, as well as methods of their preparation. Their affinities for sigma (σ1 and σ2) receptors are described. Two new compounds, N-(9-(4-aminobutyl)-9-azabicyclo[3. 3. 1]nonan-3α-yl)-N′-(2-methoxy-5-methylphenyl)carbamate and N-(9-(6-aminohexyl)-9-azabicyclo[3. 3. 1]nonan-3α-yl)-N′-(2-methoxy-5-methylphenyl)carbamate, are shown to have a high affinity and selectivity for σ2 versus σ1 receptors. Among the disclosed compounds are biotinylated and fluorescent analogs. These compounds can serve as probes to the σ2 receptor. In addition, some disclosed compounds can induce apoptotic cell death by both caspase-dependent and caspase-independent mechanisms, and are effective for treatment of tumors. The compounds can be used as chemotherapeutics or chemosensitizers in the treatment of a wide variety of solid tumors.

8461311, Jun 11, 2013

Jun 8, 2011

13/155577

William G. Hawkins - Olivette MO, US
Dirk Spitzer - Webster Groves MO, US
Richard S. Hotchkiss - Chesterfield MO, US

Washington University - Saint Louis MO

C07K 14/52, C07K 14/47, C07K 16/46

530402, 530350, 530300, 530324, 5303873, 5303919, 514 189

Disclosed are TNF-related apoptosis-inducing ligand (TRAIL) trimers (TR3) and nucleic acids encoding covalently linked TRAIL trimers. A TRAIL trimer can have greater stability compared to native TRAIL, and can retain the native killing ability of TRAIL. Target specificity of a TR3 can be shown by blocking its activity with soluble death receptor 5 (DR5-Fc). Also disclosed are modified TRAIL trimers and nucleic. acids encoding them. These modifications include additional functional domains, such as antibody fragments (scFvs). A TR3 comprising an additional functional domain can allow for cell-specific delivery of the TR3. The inventors disclose TR3-decorated RBCs that target cell killing in a model of pancreatic cancer.