Methods of treating malignant lymphoproliferative disorders in a patient, comprising administering an effective amount of a GSK-3β inhibitor, for example 9-ING-41, are provided. Also provided are methods for treating malignant lymphoproliferative disorders comprising administering a ({umlaut over (.Math.)}8K-3β inhibitor, for example 9-ING-41, in combination with a second or multiple therapeutic agents.

Methods of treating malignant lymphoproliferative disorders in a patient, comprising administering an effective amount of a GSK-3β inhibitor, for example 9-ING-41, are provided. Also provided are methods for treating malignant lymphoproliferative disorders comprising administering a ({umlaut over (.Math.)}8K-3β inhibitor, for example 9-ING-41, in combination with a second or multiple therapeutic agents.

Methods of treating malignant lymphoproliferative disorders in a patient, comprising administering an effective amount of a GSK-3β inhibitor, for example 9-ING-41, are provided. Also provided are methods for treating malignant lymphoproliferative disorders comprising administering a ({umlaut over (.Math.)}8K-3β inhibitor, for example 9-ING-41, in combination with a second or multiple therapeutic agents.

Currently available glutaminase inhibitors are generally poorly soluble, metabolically unstable, and/or require high doses, which together reduce their efficacy and therapeutic index. These can be formulated into nanoparticles and delivered safely and effectively for treatment of pancreatic cancer and other glutamine addicted cancers. Studies demonstrate that nanoparticle delivery of BPTES, relative to use of BPTES alone, can be safely administered and provides dramatically improved tumor drug exposure, resulting in greater efficacy. GLS inhibitors can be administered in higher concentrations with sub-100 nm nanoparticles, since the nanoparticles package the drug into “soluble” colloidal nanoparticles, and the nanoparticles deliver higher drug exposure selectively to the tumors due to the enhanced permeability and retention (EPR) effect. These factors result in sustained drug levels above the IC50 within the tumors for days, providing significantly enhanced efficacy compared to unencapsulated drug.

Currently available glutaminase inhibitors are generally poorly soluble, metabolically unstable, and/or require high doses, which together reduce their efficacy and therapeutic index. These can be formulated into nanoparticles and delivered safely and effectively for treatment of pancreatic cancer and other glutamine addicted cancers. Studies demonstrate that nanoparticle delivery of BPTES, relative to use of BPTES alone, can be safely administered and provides dramatically improved tumor drug exposure, resulting in greater efficacy. GLS inhibitors can be administered in higher concentrations with sub-100 nm nanoparticles, since the nanoparticles package the drug into “soluble” colloidal nanoparticles, and the nanoparticles deliver higher drug exposure selectively to the tumors due to the enhanced permeability and retention (EPR) effect. These factors result in sustained drug levels above the IC50 within the tumors for days, providing significantly enhanced efficacy compared to unencapsulated drug.

Currently available glutaminase inhibitors are generally poorly soluble, metabolically unstable, and/or require high doses, which together reduce their efficacy and therapeutic index. These can be formulated into nanoparticles and delivered safely and effectively for treatment of pancreatic cancer and other glutamine addicted cancers. Studies demonstrate that nanoparticle delivery of BPTES, relative to use of BPTES alone, can be safely administered and provides dramatically improved tumor drug exposure, resulting in greater efficacy. GLS inhibitors can be administered in higher concentrations with sub-100 nm nanoparticles, since the nanoparticles package the drug into “soluble” colloidal nanoparticles, and the nanoparticles deliver higher drug exposure selectively to the tumors due to the enhanced permeability and retention (EPR) effect. These factors result in sustained drug levels above the IC50 within the tumors for days, providing significantly enhanced efficacy compared to unencapsulated drug.

The present disclosure, for example, can include a laminated type patch A, comprising a release layer 1, a drug layer 2, a drug support layer 3 having elasticity, an adhesive layer 4, and an adhesive support layer 5 laminated in this order, wherein the outer edges of the release layer, the adhesive layer, and the adhesive support layer are all outside the outer edges of both the drug layer and the drug support layer; wherein the portion surrounded by the outer edges of the drug layer and the drug support layer, and the inner sides of the release layer and the adhesive layer has a space; and wherein the cross-sectional area of the space is 0.3 mm2 or more, at least when cut along the longitudinal centerline and the transverse centerline on the plane surfaces of the drug layer and the drug support layer.

The present disclosure, for example, can include a laminated type patch A, comprising a release layer 1, a drug layer 2, a drug support layer 3 having elasticity, an adhesive layer 4, and an adhesive support layer 5 laminated in this order, wherein the outer edges of the release layer, the adhesive layer, and the adhesive support layer are all outside the outer edges of both the drug layer and the drug support layer; wherein the portion surrounded by the outer edges of the drug layer and the drug support layer, and the inner sides of the release layer and the adhesive layer has a space; and wherein the cross-sectional area of the space is 0.3 mm2 or more, at least when cut along the longitudinal centerline and the transverse centerline on the plane surfaces of the drug layer and the drug support layer.

The present disclosure provides compositions and methods for reactivating latent immunodeficiency virus using a glycogen synthase kinase 3α inhibitor, such as a glycogen synthase kinase 3α (GSK-3α) or a glycogen synthase kinase 3β (GSK-3β) inhibitor. In some embodiments, the glycogen synthase kinase 3 inhibitor is a glycogen synthase kinase antagonist, e.g., Tideglusib (4-benzyl-2-(naphthalen-1-yl)-1,2,4-thiadiazolidine-3,5-dione), or a pharmaceutically acceptable salt or derivative thereof. In other embodiments, the glycogen synthase kinase 3 inhibitor is a maleimide-based glycogen synthase kinase 3 inhibitor, e.g., SB-216763 (3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione) or a pharmaceutically acceptable salt or derivative thereof.

The present disclosure provides compositions and methods for reactivating latent immunodeficiency virus using a glycogen synthase kinase 3α inhibitor, such as a glycogen synthase kinase 3α (GSK-3α) or a glycogen synthase kinase 3β (GSK-3β) inhibitor. In some embodiments, the glycogen synthase kinase 3 inhibitor is a glycogen synthase kinase antagonist, e.g., Tideglusib (4-benzyl-2-(naphthalen-1-yl)-1,2,4-thiadiazolidine-3,5-dione), or a pharmaceutically acceptable salt or derivative thereof. In other embodiments, the glycogen synthase kinase 3 inhibitor is a maleimide-based glycogen synthase kinase 3 inhibitor, e.g., SB-216763 (3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione) or a pharmaceutically acceptable salt or derivative thereof.