Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.

Tyrnovo Ltd.

Novotyr Therapeutics Ltd.

Hadasit Medical Research Services and Development Ltd.

Develogen Israel Ltd.

Hadas Reuveni

Alexander Levitzki

Shmuel A Ben-Sasson

Revital Sasson

Ehud Cohen

Lana Kupershmidt

Izhak Haviv

Chaim Gilon

Andre C B Lucassen

Iris Ben-David

Nurit Livnah

Eleazar Shafrir

Ehud Ziv

Masha Niv

Lilach Steiner

Avi Weissberg

Alexander Levitski

Provided is a treatment of cancer using a dual modulator of Insulin Receptor Substrate (IRS) and signal transducer and activator of transcription 3 (Stat3), as well with other agents. The combination can be used to treat a tumor that has developed resistance to an EGFR inhibitor, EGFR antibody, mTOR inhibitor, MEK inhibitor, mutated B-Raf inhibitor, chemotherapeutic agents, and certain combinations thereof, or to prevent acquired resistance of a tumor to any of said inhibitors or agents, or to prevent tumor recurrence following cease of treatment with any of said inhibitors or agents or a combination thereof. The subject matter further provides a treatment of cancer using combination therapy comprising a dual modulator of IRS and Stat3, in combination with an immunotherapy agent. The combination can be used to sensitize a tumor to immunotherapy.

Combinations of IRS/STAT3 dual modulators and anti-cancer agents for treating cancer

Combinations of IRS/Stat3 dual modulators and anti-cancer agents for treating cancer

The present invention provides compounds acting as Insulin/IGF signaling modulators useful in the treatment of neurodegenerative diseases and disorders. The invention provides pharmaceutical compositions including such compounds, and methods of using these compounds and compositions for the treatment of neurodegenerative diseases, in particular neurodegenerative diseases caused by proteotoxicity such as Alzheimer's disease.

IGF-1R signaling pathway inhibitors useful in the treatment of neurodegenerative diseases

Short bioactive sequences derived from the 2loop of the 7-transmembranal receptor of endothelial differentiation gene 3 (EDG3) useful in stimulation of angiogenesis, and peptide conjugates comprising a permeability enhancing moiety, are provided. Also provided are pharmaceutical compositions comprising the peptides and methods of use in conditions were insufficient blood-supply occurs, or which are associated with endothelia dysfunction such as peripheral vascular diseases, coronary artery diseases, cerebrovascular diseases, diabetes and delayed wound healing, pulmonary disease, eye diseases and pathological condition related to severe infection.

Pro-angiogenic peptides and peptide conjugates

The present invention provides compounds of formula (1) acting as protein kinase (PK) and receptor kinase (RK) signaling modulators. The invention further provides methods of their preparation, pharmaceutical compositions including such compounds, and methods of using these compounds and compositions, especially as anti-cancer agents for preventions and treatments of PK- and RK-related disorders, in particular cancer. (I) wherein A is H or CN; Z is S, SO or S0; X, X, X, X, X, Yand Yare each independently selected from H, halogen, alkyl, haloalkyl and OR; and Yand Yare each OR, wherein each Ris independently H, C-Calkyl, acyl, &#x2014;(CHCH0)wherein n is an integer of 1 to 20, or a functional group that gives rise to hydroxyl upon hydrolysis. 

2-(2-phenylethenyl) 1,3-benzodiazepine derivatives useful for the treatment of cancer

The present invention provides new tyrphostin derivatives acting as protein kinase (PK) and receptor kinase (RK) signaling modulators. The invention further provides methods of their preparation, pharmaceutical compositions including such compounds, and methods of using these compounds and compositions, especially as chemotherapeutic agents for preventions and treatments of PK and RK related disorders such as metabolic, inflammatory, fibrotic, and cell proliferative disorders, in particular cancer.

Modulators of protein kinase signaling

The present invention provides peptides and peptide analogs capable of inhibiting the activity of protein kinase C. The invention discloses use of such peptides and analogs for preparation of pharmaceutical compositions and methods for prevention, delay, suppression or treatment of type 2 diabetes using such compositions.

Protein kinase C inhibitors for prevention of insulin resistance and type 2 diabetes

The present invention provides new tyrphostin derivatives acting as substrate competitive protein tyrosine kinase (PTK) inhibitors and receptor tyrosine kinase (RTK) inhibitors, methods of their preparation, pharmaceutical compositions including such compounds, and methods of using these compounds and compositions, especially as chemotherapeutic agents for preventions and treatments of PTK and RTK related disorders such as metabolic, fibrotic, and cell proliferative disorders, in particular psoriasis and cancer.

Protein kinase modulators and therapeutic uses thereof

The present invention concerns compounds comprising, within short sequences from a specific regions of the 7TM receptor, that can modulate 7TM receptor-associated signal. The present invention further concerns methods for stimulation angiogenesis by administration of peptides derived from the EDG3 7TM-receptor.

[object Object]

Novel isoquinoline derivatives which are useful as inhibitors of protein kinases for experimental, medical, and drug design purposes are disclosed. Preferred compounds which are specific inhibitors of protein kinase B are also disclosed. Furthermore, pharmaceutical compositions comprising these protein kinase inhibitors, and methods of using such compositions for treatment and diagnosis of cancers, diabetes, cardiovascular pathologies, hemorrhagic shock, obesity, inflammatory diseases, diseases of the central nervous system, and autoimmune diseases, are also disclosed.

Protein kinase inhibitors

A farnesyl protein transferase (i.e., farnesyltransferase) inhibitors formed as peptoid and semipeptoid peptidomimetic compounds derived from a farnesyltransferase universal recognition tetrapeptide sequence CAAX (i.e., CAAX motif) and analogs thereof, and to the use of these compounds and analogs and ester derivatives thereof as chemotherapeutic agents in oncogenic or non-oncogenic Ras associated cancers and proliferative diseases.

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Har Adar, Israel

Hadas Reuveni