The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.

Disclosed is the use of a checkpoint kinase (CHK) inhibitor in combination with i) a poly(ADP)-ribose polymerase inhibitor, and optionally ii) a chemotherapeutic agent such as gemcitabine, in cancer treatment.

Disclosed is the use of a checkpoint kinase (CHK) inhibitor in combination with i) a poly(ADP)-ribose polymerase inhibitor, and optionally ii) a chemotherapeutic agent such as gemcitabine, in cancer treatment.

Disclosed is the use of a checkpoint kinase (CHK) inhibitor in combination with i) a poly(ADP)-ribose polymerase inhibitor, and optionally ii) a chemotherapeutic agent such as gemcitabine, in cancer treatment.

The invention herein discloses a pharmaceutical combination for use in the treatment of cancer comprising a DNA ligase IV inhibitor and a PARP inhibitor in synergistically effective amounts for simultaneous, separate or sequential administration to a subject in need thereof.

The invention herein discloses a pharmaceutical combination for use in the treatment of cancer comprising a DNA ligase IV inhibitor and a PARP inhibitor in synergistically effective amounts for simultaneous, separate or sequential administration to a subject in need thereof.

The invention herein discloses a pharmaceutical combination for use in the treatment of cancer comprising a DNA ligase IV inhibitor and a PARP inhibitor in synergistically effective amounts for simultaneous, separate or sequential administration to a subject in need thereof.

Compounds described herein may be used for the treatment of neurodegenerative diseases linked to protein misfolding, including prion diseases, Alzheimer's disease, Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), and also other neurodegenerative, degenerative, metabolic and ischemic conditions. Indeed, NAD metabolism impairment is also a critical feature in brain ischemia/reperfusion injury, Wallerian degeneration, kidney failure, multiple sclerosis, aging, and metabolic disorders such as diabetes mellitus. Therapies that elevate or stabilize NAD levels may thus have broad potential for treating many severely debilitating neurological and metabolic conditions. Evidence is provided herein with compounds from 8 lead series for NAD restoring properties and for therapeutic efficacy in cellular and/or animal models of prion disease, PD and ALS.