Parker Hughes Institute

Regents of the University of Minnesota

Hughes Institute

Wayne Hughes Institute

Other

Ares Pharmaceuticals, LLC

Rutgers, the State University of New Jersey

Fatih M Uckun

Xing-Ping Liu

Osmond D'Cruz

Elise A Sudbeck

Rama Krishna Narla

Ravi Malaviya

Yaguo Zheng

Sutapa Ghosh

Taracad K Venkatachalam

Phalguni Ghosh

Shyi-Tai M Jan

Ravi Malavia

Rakesh Vig

Chen Mao

Taracad K Ventatachalam

Vuong N Trieu

Taracad Venkatachalam

Yanhong Dong

Phalguni Gosh

Marina Cetkovic

Peter M Anderson

Russell Drew Cink

Nilgun Ereken Tumer

Keqiang Li

Mark D Williams

Vuoung N Trieu

He Huang

Wanhong Dong

Alexcy O Benyumov

Chun-Lin Chen

Zhoa-Hai Zhu

Feryan Ahmed

Craig Forsyth

Zhaohai Zhu

De-Min Zhu

Mya L Crotty

Chi Sing Lee

David Alan Perry

Alexander Rostovstev

Shyi-Tai Jan

Synthetic, novel dimeric cinchona alkaloid compounds having potent cytotoxic activity against human cancer cells. The compounds are effective agents for inhibiting cellular proliferation, for example, in cancer cells. The compounds cause apoptotic cell death in and cause inhibition of clonogenic growth of human breast cancer, prostate cancer, leukemia, lymphoma cells at nanomolar concentrations. The chemical structure of the compound includes dimeric cinchona alkaloid and derivatives containing various groups attached in their structure. The compounds also possess hydroxy group functionality in the structure to enable the preparation of pharmaceutically applicable salts to enhance their solubility for ease of systemic administration in animals and in humans, for example, in cancer patients.

Synthetic dimeric cinchona alkaloids against cancer

Novel cinchona alkaloid compounds have been synthesized and discovered to have potent cytotoxic activity against cancer cells both in vitro and in vivo. Cinchona alkaloids, including trimeric cinchona alkaloids as well as their polymers can be used as catalysts of complex chemical reactions in organic chemistry, for example for the enantioselective desymmetrization of cyclic anhydrides, asymmetric synthesis of amino acids (Ayyanar Siva, Eagambaram Murugan. Synthesis 2005; 17:2927-2933; Hyeung-geun Park et al. Tetrahedron Letters, Volume 42, Issue 28, 2001, Pages 4645-4648; Shohei Takata et al., RSC Adv., 2016, 6, 72300-72305; Masud Parvez et al., Macromolecules 2014, 47, 6, 1922-1928; Marcelli, T. 2007, UvA-DARE (Digital Academic Repository). https://pure.uva.nl/ws/files/4416997/52576_marcelli_thesis.pdf Compounds described herein exhibit broad-spectrum therapeutic efficacy against different cancer types, including leukemias/lymphomas, prostate cancer, breast cancer, malignant melanoma, aggressive brain tumor/glioblastoma multiforme (GBM), non-small cell lung cancer. The chemical structure of the compounds includes a trimeric cinchona alkaloid and derivatives containing various groups attached in their structure.

Synthetic cinchona alkaloids against cancer

The present invention is directed to compounds and methods suitable for the treatment of HIV infection.

NNI for treatment of multi-drug resistant HIV

Methods of inhibiting virus replication of in a cell infected with a resistant strain of HIV that includes administering to the infected cell a virus replication inhibiting amount of an aryl phosphate derivative of d4T.

Aryl phosphate derivatives of d4T having activity against resistant HIV strains

The invention provides methods for treating cancer and compounds that are useful for the treatment of tumors, as well as pharmaceutical compositions comprising the compounds, and synthetic methods and intermediates useful for preparing the compounds.

Vanadium compounds for treating cancer

Compounds are described that bind to tubulin causing tubulin depolymerization and inhibiting tubulin polymerization. The compounds of the invention are therapeutically effective to inhibit cellular proliferation, for example, as effective anti-cancer agents. The compounds can also induce cytotoxicity in cells such as leukemia cells. The chemical structure of the compounds includes a furan, thiophene, thiazole, oxazole, or imidazole group at one end of the molecule (head) and a hydrophobic, aliphatic chain at the other end of the molecule (tail).

Cytotoxic compounds

The present disclosure includes compounds, for example a compound according to formula Ior a pharmaceutically acceptable salt thereof. The compounds of the present disclosure are useful in methods of treating cancerous conditions.

Haloanilino quinazolines and therapeutic use thereof

Vanadium compounds for inhibiting angiogenesis useful for treating or preventing diabetic retinopathy, hemangiomas, cancers with abnormal blood vessel supply, restenosis following vascular injury, and the like.

Vanadium compounds as anti-angiogenic agents

A transgenic zebrafish animal model is disclosed. The model can be used for study of hematopoetic cell differentiation, control, and screening of therapeutic agents and can include a transgenic zebrafish expressing a heterologous Ikaros protein.

Transgenic zebra fish embryo model for hematopoiesis and lymphoproliferative disorders

Inhibitors of JAK3 kinase for the treatment of allergy, and others are described.

JAK-3 inhibitors for treating allergic disorders

Vanadium compounds useful to prevent and/or inhibit adhesion, migration, and invasion of proliferative cells into surrounding tissue.

Vanadium compounds for treating proliferative cell disorders

Novel compounds and pharmaceutical compositions useful as EGFR tyrosine kinase inhibitors. Methods of the invention include administration of the EGFR TK inhibitors to treat diseases characterized by enhanced expression of EGF, including cancers, particularly breast cancer. Additionally, a homology model representing the structure of EGFR kinase domain is provided, which model is useful for the rationally design and screening of compounds predicted to bind favorably to EGFR and to inhibit EGFR TK.

Inhibitors of the EGF-receptor tyrosine kinase and methods for their use

Methods for increasing the elimination half-life of key metabolites such as d4T by administering an aryl phosphate derivative of d4T having an electron withdrawing substituent on the aryl group and an amino acid substituent on the phosphate group are described. A preferred aryl phosphate derivative of d4T is HI-113 (d4T-5&prime;-&lsqb;p-bromophenyl methoxyalaninyl phosphate&rsqb;). The administration of HI-113 results in more prolonged systemic exposure to the key metabolites, Ala-d4T-MP and d4T, than administration of an equimolar dose of either metabolite. Each metabolite has a significantly longer elimination half life when formed in vivo from the administration of HI-113 than when the metabolite is administered directly.

Aryl phosphate derivatives of d4T with potent anti-viral activity

The invention provides a method for inhibiting c-jun activation in mammalian or avian cells comprising contacting the cells with a substance that inhibits the activity of Janus family kinase 3 (JAK-3). The invention also provides a therapeutic method for preventing or treating a pathological condition in a mammal wherein c-jun activation is implicated and inhibition of its activation is desired comprising administering to a mammal in need of such therapy, an effective amount of a substance that inhibits the activity of JAK-3. Novel compounds that are JAK-3 inhibitors, as well as pharmaceutical compositions comprising the compounds are also provided.

Method for inhibiting c-jun expression using JAK-3 inhibitors

Synthetic Phorboxazole A and derivatives thereof for the treatment of cancer, including inhibition of cancer cell growth, induction of apoptosis, and inhibition of metastises.

Phorboxazole derivatives for treating cancer

Growing community of inventors

White Bear Lake, MN, United States of America

Fatih M Uckun