City of Hope

University of South Florida

University of California

Yale University

National and Kapodistrian University of Athens

Johns Hopkins University

University of Central Florida Research Foundation Inc

Richard Jove

Hua Yu

Sangkil Nam

Said M Sebti

David A Horne

James Turkson

Jun Xie

Marcin Tomasz Kortylewski

John J Rossi

Piotr Marek Swiderski

Andrew D Hamilton

Larry Eugene Overman

Jay W Palmer

Heidi Kay

Claudia Kowolik

Marcus Baumann

Drew M Pardoll

Rongzhen Xu

Angela L Perkins Harki

Wendong Huang

Leandros Skaltsounis

Richard M Heller

Mark Jeffrey Jaroszeski

Richard A Gilbert

William S Dalton

Christopher Lincoln

Eric Bruce Haura

Daniel M Sullivan

Alexios-Leandros Skaltsounis

Gerold Bepler

Nicolas Gaboriaud-Kolar

Alexios Leandros Skaltsounis

Susan E Minton

Carlos A Muro-Cacho

Marina Kritsanida

Kenichi Yakushijin

Fumiko Y Yakushijin

David Horne

Indirubin is the major active anti-tumor component of a traditional Chinese herbal medicine used for treatment of chronic myelogenous leukemia (CML). Indirubin derivatives (IRDs) potently reduce the viabilities of various cancer cells and affect kinase activities. IRDs disclosed herein provide new therapeutics for cancer and conditions regulated by the kinase activities.

Indirubin derivatives, and uses thereof

Disclosed herein inter alia are compositions and methods for treating cancer using 5-Br-indirubin derivatives.

5-bromo-indirubins

The present invention relates to methods and compositions for the treatment of diseases, including cancer, infectious diseases and autoimmune diseases. The present invention also relates to methods and compositions for improving immune function. More particularly, the present invention relates to multifunctional molecules that are capable of being delivered to cells of interest for the treatment of diseases and for the improvement in immune function.

Methods and compositions for the treatment of cancer or other diseases

Provided herein, inter alia, is the synthesis of ETP derivatives. The uses of the ETP derivatives described herein include treatment of cancer.

ETP derivatives

One aspect of the invention relates to novel isatin derivative compounds and the pharmaceutical composition thereof. Another aspect of the invention relates to methods of using the isatin derivative compounds disclosed herein and the pharmaceutical compositions thereof. In certain embodiments, the method is used to treat a cancer or a tumor in a subject including, without limitation, prostate cancer, melanoma, pancreatic cancer, ovarian cancer, and lymphoma. In certain embodiment, the method is used to treat a condition in a subject that can be regulated by the activation of one or more proteins such as EGFR, Erk1/2, Her2/Neu, Jak2, Src, Stat3, Akt, Cyclin B1, and Cdc25C. In certain embodiment, the method is used to treat a condition in a subject that can be regulated by the disruption of microtubule formations.

Isatin derivatives, pharmaceutical compositions thereof, and methods of use thereof

Indirubin is the major active anti-tumor component of a traditional Chinese herbal medicine used for treatment of chronic myelogenous leukemia (CML). One aspect of the invention relates to a method of treating CML using at least one indirubin derivative compound or a pharmaceutical composition thereof. Indirubin derivatives (IRDs) potently inhibited Signal Transducer and Activator of Transcription 5 (Stat5) protein in CML cells. Compound IRD 810 inhibits Bcr-Abl/Stat5 or Src/Stat5 signaling in human KCL-22 CML and imatinib-resistant human KCL-22 CML cells expressing the T315I mutant Bcr-Abl. Previous studies indicate that SFKs cooperate with Bcr-Abl to activate downstream Stat5 signaling. Activation of Stat5 was strongly blocked by IRD 810 in CML cells. IRDs disclosed herein have been identified as potent inhibitors of Bcr-Abl/Stat5 or SFK/Stat5 signaling pathway. IRDs disclosed herein are new therapeutics for wild type or T315I mutant Bcr-Abl-positive CML patients, and may also treat other solid tumors, including prostate cancer and lymphoma.

Indirubin derivatives and uses thereof in treating chronic myelogenous leukemia

Signal Transducer and Activator of Transcription (STAT) proteins have a fundamental role cell signaling, and are activated by a large number of cytokines and growth factors. One member of the STAT family, STAT3, has a critical role in oncogenesis. The present invention relates generally to disruption of the pathway of STAT3 signaling in the treatment of human cancer. STAT3 activation is shown to be present in diverse tumor cell lines and tumors, to promote oncogenesis, to inhibit apoptosis, and to reduce sensitivity to chemotherapeutic agents. Inhibition of STAT3 signaling induces apoptosis specifically in tumor cell lines, and increases sensitivity to chemotherapeutic agents. The invention relates more particularly to methods, compositions, means of administering such compositions, and means for identifying such compositions for the inhibition of STAT3 intracellular signaling in the treatment of human cancers.

Inhibition of STAT3 signal transduction for human cancer therapy

The invention provides novel berbamine derivatives, and compositions or pharmaceutical compositions thereof. These berbamine derivatives have shown higher potency in killing cancer/tumor cells comparing to berbamine, and can be used in cancer/tumor treatments.

Berbamine derivatives

Growing community of inventors

Glendora, CA, United States of America

Richard Jove