University of South Florida

H. Lee Moffitt Cancer Center and Research Institute, Inc.

Yale University

University of Pittsburgh

University of Central Florida Research Foundation Inc

Torrey Pines Institute for Molecular Studies

Other

The United States Government as Represented by the Department of Veterans Affairs

Chongqing Zein Pharmaceutical Co., Ltd

University of Florida Research Foundation Inc

New York University

Jin Q. Cheng

Said M. Sebti

Said M Sebti

Jin Q Cheng

Andrew D Hamilton

Nicholas James Lawrence

Harshani Lawrence

James Turkson

Richard Jove

Wayne Charles Guida

Rongshi Li

Wang Shen

Kenneth Jay Barr

Saul H Rosenberg

Stephen J O'Connor

Ernst Schönbrunn

Stephen A Fakhoury

Benjamin Greedy

Man Lun Yip

Richard Allen Houghten

Le Wang

Gerard M Sullivan

David John Augeri

Jianfeng Cai

Jay W Palmer

Katherine J Kayser-Bricker

Kenneth J Henry

James T Wasicak

Yan Liu

Joseph A Stanko

Jie Wu

Yangmei Li

Andrew Stewart Tasker

Bryan K Sorensen

Heidi Kay

Douglas M Kalvin

Rolf E Swenson

Juan Sanchez-Ramos

Srikumar Chellappan

Indrani W Gunawardana

Mokenge P Malafa

Shijie Song

Claudio Anasetti

Yong Qin

David A Janowick

Hao Song

Vasyl Sava

Lissa T J Nelson

Chunwei Cheng

Brian Betts

Rishi Kumar Jain

Mei Sun

Joseph Pidala

Churl Min Seong

Matthew P Martin

Roberta Pireddu

Jalila Adnane

Rosalind J Jackson

Sevil Ozcan

Yiyu Ge

Gang Liu

Richard M Heller

Mark Jeffrey Jaroszeski

Richard A Gilbert

Hua Yu

Hairuo Peng

John S Lazo

Michele Pagano

William S Dalton

W Jack Pledger

Warren Jackson Pledger

Julia R Burdge

Jitesh P Jani

Gregory Springett

Jehangir S Mistry

Terence F McGuire

Bryan K Sorenson

Bruce G Szczepankiewicz

Greg B Donner

Shafi Kuchay

James I Wasick

Bernard G Donner

John J Larsen

Stephen J O'CONNOR

Rishi Jain

Disclosed herein are compounds and methods for reducing the risk of developing, preventing, or treating graft versus host disease (GVHD) in a subject. The compounds can concurrently block Aurora kinase A and JAK2 signal transduction which synergistically suppresses alloreactive human T-cells in vitro, prevents xenogeneic graft-versus-host disease without impairing anti-tumor responses, and promotes the development and suppressive potency of CD39+ inducible T. In certain aspects, disclosed are compounds of Formula I-V.

Aurora kinase and janus kinase inhibitors for prevention of graft versus host disease

A method is disclosed for treating a cancer in a subject that involves administering to the subject a therapeutically affective amount of a geranylgeranyltransferase I (GGTase I) inhibitor, such as GGTI-2418, wherein the cancer comprises a defective PTEN, a hyperactivated FBXL2, or a low level of IP3R3. In some embodiments, the method further involves administering to the subject a therapeutically affective amount of an Akt inhibitor.

Geranylgeranyltransferase I inhibitor for treatment of a PTEN defective cancer

The subject invention concerns a compound and compositions having activity as an inhibitor of Stat3 protein and methods of using the compound and compositions. In one embodiment, a compound of the invention has the structure shown in formula I, formula II, or formula III. The subject invention also concerns methods of using the compounds and compositions of the invention.

Platinum compounds that inhibit constitutive STAT3 signaling and induce cell cycle arrest and apoptosis of malignant cells

Compositions and methods for inhibits the binding of GTP to oncogenic mutant KRas are disclosed. These compositions may be used in method to treat a subject with cancer. In particular, the compositions may be used to treat cancers involving overactive Ras signaling.

Mutant KRAS inhibitors

Disclosed herein are compounds and methods for reducing the risk of developing, preventing, or treating graft versus host disease (GVHD) in a subject. The compounds can concurrently block Aurora kinase A and JAK2 signal transduction which synergistically suppresses alloreactive human T-cells in vitro, prevents xenogeneic graft-versus-host disease without impairing anti-tumor responses, and promotes the development and suppressive potency of CD39+ inducible T. In certain aspects, disclosed are compounds of Formula I-V. 

Aurora kinase and Janus kinase inhibitors for prevention of graft versus host disease

The subject matter disclosed herein relates to compositions and methods of making and using the compositions. In a further aspect, the subject matter disclosed herein relates to inhibitors of STAT3 dimerization. Methods of making these compositions as well as compositions comprising these compositions are also disclosed. Also disclosed are methods of treating or preventing certain cancers by administering to an individual in need thereof and effective amount of the compounds disclosed herein. Still further, disclosed herein are methods of inhibiting STAT3 by contacting a cell with a compound or composition as disclosed herein.

STAT3 dimerization inhibitors

Methods of inducing tumor regression, inhibiting tumor growth, and inducing apoptosis with selective peptidomimetic inhibitors of geranylgeranyltransferase I (GGTase I), are provided. In one aspect, GGTI-2418 and its methylester GGTI-2417, increase levels of the cyclin-dependent kinase (Cdk) inhibitor p27and induce breast tumor regression in vivo. In another aspect, GGTI-2417 inhibits the Cdk2-mediated phosphorylation of p27at Thr187 and accumulates p27in the nucleus.

Methods for inducing tumor regression, inhibiting tumor growth, and inducing apoptosis in breast tumors with geranylgeranyltransferase I inhibitors

Described herein are compound for the modulation of the G-CSF receptor. The compounds may act as agonists, antagonists, and/or mixed or partial agonists/antagonists of G-CSF. Further provided herein are methods of treating a condition, including, for example, a neurodegenerative disease, by administering a compound as detailed herein.

Small molecules that mimic or antagonize actions of granulocyte colony-stimulating-factor (G-CSF)

The present invention concerns compounds, compositions containing these compounds, and methods of using these compounds and compositions as inhibitors of Stat3 signaling, Stat3 dimerization, Stat3-DNA binding, Stat5-DNA binding, and/or aberrant cell growth in vitro or in vivo, e.g., as anti-cancer agents for treatment of cancer, such as breast cancer. The compounds of the invention include, but are not limited to, NSC 74859 (S3I-201), NSC 42067, NSC 59263, NSC 75912, NSC 11421, NSC 91529, NSC 263435, and pharmaceutically acceptable salts and analogs of the foregoing. Other non-malignant diseases characterized by proliferation of cells that may be treated using the compounds of the invention, but are not limited to, cirrhosis of the liver; graft rejection; restenosis; and disorders characterized by a proliferation of T cells such as autoimmune diseases, e.g., type 1 diabetes, lupus and multiple sclerosis. The invention further includes an in-vitro screening test for the presence of malignant cells in a mammalian tissue; a method of identifying inhibitors of constitutive Stat3 activation, Stat3-DNA binding, Stat5-DNA binding, and/or Stat3 dimerization; and a method of identifying anti-cancer agents.

Small molecule inhibitors of STAT3 with anti-tumor activity

This application relates to combination therapies including triciribine compounds and epidermal growth factor receptor inhibitor compounds, particularly erlotinib-like compounds and compositions with reduced toxicity for the treatment and prevention of tumors, cancer, and other disorders associated with abnormal cell proliferation.

Compositions including triciribine and epidermal growth factor receptor inhibitor compounds or salts thereof and methods of use thereof

Methods of treating breast cancer that overexpress AKT kinase

Mutant KRas inhibitors

Focused library synthesis and medicinal chemistry on an oxadiazole-isopropylamide core proteasome inhibitor provided the lead compound that strongly inhibits CT-L activity. Structure activity relationship studies indicate the amide moiety and two phenyl rings are sensitive toward synthetic modifications. Only para-substitution in the A-ring was important to maintain potent CT-L inhibitory activity. Hydrophobic residues in the A-ring's para-position and meta-pyridyl group at the B-ring significantly improved inhibition. The meta-pyridyl moiety improved cell permeability. The length of the aliphatic chain at the para position of the A-ring is critical with propyl yielding the most potent inhibitor, whereas shorter (i.e. ethyl, methyl or hydrogen) or longer (i.e. butyl, propyl and hexyl) chains demonstrating progressively less potency. Introduction of a stereogenic center next to the ether moiety (i.e. substitution of one of the hydrogens by methyl) demonstrated chiral discrimination in proteasome CT-L activity inhibition (the S-enantiomer was 35-40 fold more potent than the R-enantiomer).

Proteasome chymotrypsin-like inhibition using PI-1833 analogs

Stapled peptides and methods of using them to inhibit the Kras/Raf interaction are disclosed herein.

Methods and compositions related to KRAS inhibitors

Growing community of inventors

Tampa, FL, United States of America

Said M Sebti