The University of New Mexico

University of Kansas

Ball State Innovation Corporation

Torrey Pines Institute for Molecular Studies

University of Michigan

Health Research, Inc.

Sanford-burnham Medical Research Institute

Intellicyt Corporation

Larry A Sklar

Bruce S Edwards

Tudor Oprea

Frederick Kuckuck

Eric R Prossnitz

Angela Wandinger-Ness

Zurab Surviladze

Mark K Haynes

Laurie Hudson

Jennifer Elizabeth Golden

Chad Schroeder

Daniel F Cimino

Alexandre Chigaev

Jeffrey Aube

Snezna Rogelj

Peter C Simons

Denise S Simpson

Robert E Sammelson

Susan A McDowell

Richard Allen Houghten

Clemencia Pinilla

Jacob Ongudi Agola

Jon Richard Appel

Jeffrey Arterburn

Marc A Giulianotti

Susan M Young

Teresa A Bennett

Ronald D Salesky

Dominique Perez

Frederick W Kuckuck, Iii

Donna Neldon

Chetana M Revankar

Sergey E Tkatchenko

Cristian-George Bologa

Debra Mackenzie

Todd A Thompson

Jose Medina-Franco

Anna Waller

John C Reed

Gabriel P Lopez

Ravinder K Jain

Dayong Zhai

Richard Smith Larson

Vojo P Deretic

Alexander Kiselyov

Warren S Weiner

Andrea A Mammoli

Richard Neubig

Tione Buranda

Tuanli Yao

Peter V Vorobieff

Wei Wang

Robert B Palmer

Jeffrey Aubé

Steven Bradfute

Emmanuel Rabinovich

Elizabeth Williamson

Robert A Hromas

Oleg Ursu

Eliseo F Castillo

Linda Trinkle

Julica J Noth

Larry C Seamer

Janeen Vilven

Angela-Wandinger Ness

Juan Jacob Strouse

Juchao Yan

Kimberly Opperman

Leonard Tender

Philip Hampton

Irena Ivnitski-Steele

Hadya M Khawaja

Justin Wray

Jerec Warren Ricci

Vilven Janeen

Mei Shi

Alex T Key

Sean Biggs

Richard A Truesdell

Mathewos Z Tessema

William C Burhans

Catherine E Prudom Gineste

Christopher P Allen

Alexandor Kiselyov

R Terry Dunlay

Andrei Leitao

The present invention relates to molecules which function as modulators (i.e., inhibitors and agonists) of the Ras-homologous (Rho) family of small GTPases (e.g. Rac, Cdc42 and Rho GTPases) and their use to treat diseases, including cancers (including solid tumors-medulloblastoma, ovarian, breast, head and neck, testicular, prostate among others and hematologic malignancies-B cell lymphoma, where these GTPases are overexpressed or hyperactivated), sporadic and genetic diseases where activation of Rho GTPases plays a pivotal role (Menkes disease, rheumatoid arthritis, atherosclerosis, diabetes (type I), Huntington's disease and Alzheimer's disease) which are mediated through these proteins. Compounds according to the present invention may also be used as a therapy for the treatment ofspp. orspp. infections, especially including

Modulators of GTPases and their use

The present invention is directed to previously identified inhibitors of cAMP efflux (ICE) and their use in treating/masking body odor, inhibiting, reducing and/or eliminating hyperhidrosis (excessive sweating), tanning skin or protecting skin before and/or after exposure to the sun as well as for treating certain skin conditions, in one embodiment, the invention provides a method for inhibiting body odor, a condition that is characterized by an unpleasant odor from the products of the microbial sweat degradation. By inhibiting the efflux of the precursor compounds that are degraded, novel compounds are capable of preventing unwanted odors. Deodorant compositions that employ this new approach for the control of bodily odor are provided, ICE compounds can also be used as components, of cosmetic formulations including tanning and after-sun formulations, formulations for skin conditions as described herein and other cosmetic formulations.

Application for inhibitors of cAMP efflux in body care

A flow cytometry apparatus includes a flow cytometer having a suction or negative-pressure intake probe, a support for a microplate having a plurality of sample wells, and motive elements operatively connected to at least one of the probe and the support for moving the intake probe and the support relative to one another so that the intake probe is sequentially aligned with different sample wells of the microplate. The apparatus has no fluid pumping elements between the support and the flow cytometer so that a bubble-separated sample stream is forced to the flow cytometer solely by virtue of a negative pressure communicated via the intake probe.

Flow cytometry apparatus pulling sample stream through observation chamber

The present disclosure relates to molecules that function as selective modulators (i.e., inhibitors and agonists) of the Ras-homologous (Rho) family of small GTPases and, in particular, CDC42 GTPase, and their use to treat bacterial infection including systemic infection from sources such asand

Methods for treating bacterial infection

The present invention provides novel methods and assays for high-throughput screening of combinatorial libraries to identify FPR1 and/or FPR2 ligands (e.g., agonists and/or antagonists), preferably FPR1 agonists and/or FPR2 antagonists, by positional scanning deconvolution. The invention also provides novel FPR1 and FPR2 ligands (e.g, agonists and antagonists), related pharmaceutical compositions and methods of treating FPR1 and FPR2-related disorders.

High-affinity small molecule formylpeptide receptor ligands from screening of combinatorial mixture-based libraries

In one embodiment, the invention provides a method of inhibiting cAMP efflux and increasing intracellular cAMP in a subject who suffers from, or who is at risk of developing, a cancer by administering to the subject a therapeutically-effective amount of a cAMP efflux inhibitor. Novel compounds, pharmaceutical compositions, diagnostics and screening methods are also provided.

Method for cancer cell reprogramming

The present disclosure relates to molecules which function as selective modulators (i.e., inhibitors and agonists) of the Ras-homologous (Rho) family of small GTPases and, in particular, CDC42 GTPase, and their use to treat bacterial infection including systemic infection from sources such asand

The present invention, provides a flow cytometry apparatus for the detection of particles from a plurality of samples comprising: means for moving a plurality of samples comprising particles from a plurality of respective source wells into a fluid flow stream; means for introducing a separation gas between each of the plurality of samples in the fluid flow stream; and means for selectively analyzing each of the plurality of samples for the particles. The present invention also provides a flow cytometry method employing such an apparatus.

Flow cytometry for high throughput screening

The present invention relates to molecules which function as selective modulators (i.e., inhibitors and agonists, preferably inhibitors) of the Ras-homologous (Rho) family of small GTPases, in particular, Cdc42 GTPase and their use to treat diseases, for example cancers, including metastatic cancer, where Cdc42 GTPase is overexpressed or hyperactivated, genetic and acquired diseases where activation of Cdc42 GTPase plays a pivotal role (e.g., neurodegenerative diseases), rheumatoid arthritis, atherosclerosis, diabetes type I, autosomal polycystic kidney diease, cystic kidney disease, precystic kidney disease and microbial infections. Additionally, compounds according to the present invention may be used to inhibit rejection (graft host response) in transplant patients (pursuant to transplantation), to promote immunosuppression, anti-inflammatory response and to mobilize stem cell (migration) in patients in need, among others.

Modulators of GTPase and use in relevant treatment

The invention provides methods of treating autophagy mediated diseases and disorders and related pharmaceutical compositions, diagnostics, screening techniques and kits. In one embodiment, the invention provides a method of determining whether a subject suffers from, or is at risk of developing, and autophagy mediated disease state and/or condition by evaluating LC3 levels.

Methods of treating autophagy-associated disorders and related pharmaceutical compositions, diagnostics, screening techniques and kits

This invention relates to compounds and their use as inhibitors or activators of Rab7 GTPase to treat or prevent the onset of Rab 7 GTPase-associated disorders such as neuropathies, cancer, metabolic diseases of bone and lipid storage. The invention is also applicable to infectious diseases where Rab7 is inactivated or its protein-protein interactions are modulated to facilitate intracellular survival of pathogens. The compound described acts as a competitive inhibitor of nucleotide binding and as such also has utility as a scaffold for targeting other small GTPases. In one aspect, methods of treatment of the invention are used to treat or prevent the onset of hereditary sensory neuropathies such as Charcot-Marie-Tooth type 2B disease. Related pharmaceutical compositions, assays, and drug screens are also provided.

Rab7 GTPase inhibitors and related methods of treatment

A method of treatment and/or prevention of cancer comprises administering agents which cause increased intracellular granularity in cancer cells, at least in an amount sufficient to inhibit proliferation of such cells and preferably in an amount sufficient to lead to cancer cell death. The method is particularly directed to refractory cancer, particularly hormone refractory prostate cancer. The agents identified cause increased intracellular granularity in the cancer cells, and also convert adherent cancer cells to non-adherent cancer cells, leading to cancer cell death. Using the present invention, cancer cells undergo increased intracellular granularity at relatively low agent concentrations, while also inhibiting cell proliferation. Increased concentrations lead to conversion of adherent cancer cells to non-adherent cancer cells, then to cell death. While the exact mechanism of cancer cell degradation and death is not completely understood, the treated cancer cells, including refractory prostate cancer cells, give indications of cell death through an autophagic mechanism. Pharmaceutical compositions related to the presently disclosed methods are also disclosed.

Methods and related compositions for the treatment of cancer

Growing community of inventors

Albuquerque, NM, United States of America

Larry A Sklar