Abstract: The present invention relates to the treatment of cancer using combination therapy comprising a dual modulator of Insulin Receptor Substrate (IRS) and signal transducer and activator of transcription 3 (Stat3), in combination with an antibody against programmed cell death 1 (PD-1) protein, an anti-programmed cell death protein 1 ligand (PD-L1) antibody, or a combination thereof. The combination can be used to re-sensitize a tumor that may develop or has developed resistance to the anti-PD-1 and/or anti-PD-L1 antibody, by enhancing response of the tumor to the anti-PD-1 and/or anti-PD-L1 antibody, converting non-responding tumors to responders and/or blocking tumor progression.

Abstract: 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.

Abstract: 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.

Abstract: The present invention relates to the treatment of cancer using combination therapy comprising a dual modulator of Insulin Receptor Substrate (IRS) and signal transducer and activator of transcription 3 (Stat3), in combination with an antibody against programmed cell death 1 (PD-1) protein, an anti-programmed cell death protein 1 ligand (PD-L1) antibody, or a combination thereof. The combination can be used to re-sensitize a tumor that may develop or has developed resistance to the anti-PD-1 and/or anti-PD-L1 antibody, by enhancing response of the tumor to the anti-PD-1 and/or anti-PD-L1 antibody, converting non-responding tumors to responders and/or blocking tumor progression.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: Short bioactive sequences derived from the 2nd loop 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.

Abstract: 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.

Abstract: Short bioactive sequences derived from the 2nd loop 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.

Abstract: 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.

Abstract: 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 S02; X1, X2, X3, X4, X5, Y1 and Y2 are each independently selected from H, halogen, alkyl, haloalkyl and OR1; and Y3 and Y4 are each OR1, wherein each R1 is independently H, C1-C4 alkyl, acyl, —(CH2CH20)n wherein n is an integer of 1 to 20, or a functional group that gives rise to hydroxyl upon hydrolysis.

Abstract: 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.

Abstract: 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.

Abstract: 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 S02; X1, X2, X3, X4, X5, Y1 and Y2 are each independently selected from H, halogen, alkyl, haloalkyl and OR1; and Y3 and Y4 are each OR1, wherein each R1 is independently H, C1-C4 alkyl, acyl, —(CH2CH20)n wherein n is an integer of 1 to 20, or a functional group that gives rise to hydroxyl upon hydrolysis.

Abstract: 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.

Abstract: The present invention provides new tyrphostin derivatives acting as protein tyrosine kinase (PTK) inhibitors and receptor tyrosine kinase (RTK) inhibitors, and/or which directly or indirectly affect proteins in the PTK-mediated signal transduction pathway, 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.