City of Hope

University of California

National and Kapodistrian University of Athens

Sangkil Nam

David A Horne

Richard Jove

Jun Xie

Larry Eugene Overman

Marcus Baumann

Claudia Kowolik

Rongzhen Xu

Nikolaos Lougiakis

Angela L Perkins Harki

Alexios-Leandros Skaltsounis

Wendong Huang

Ravi Salgia

Leandros Skaltsounis

Brad Loertscher

Alexios Leandros Skaltsounis

Nicolas Gaboriaud-Kolar

Christopher Lincoln

Nicole Pouli

Panagiotis Marakos

Marina Kritsanida

Kenichi Yakushijin

Fumiko Y Yakushijin

Panagiotis Gerolymatos

Disclosed herein are compositions and methods for treating cancer, FLT3-AML, and CML.

5-Bromo-indirubins

Described herein are methods for treating T-cell lymphoma in a subject in need thereof, comprising administering to the subject in need thereof, an ETP compound. Also described herein are pharmaceutical compositions and compositions for use that include such ETP compound.

T-cell lymphoma treatments

Disclosed herein, inter alia, are compositions and methods of using the same for the treatment of cancer.

Dithio ETP derivatives

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

Disclosed herein inter alia are compositions and methods for treating cancer using thioindirubin derivatives.

Thioindirubins

Disclosed herein, inter alia, are pyridopyrazines and methods of using the same.

Pyridopyrazine compounds and uses thereof

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.

Growing community of inventors

Tujunga, CA, United States of America

Sangkil Nam