This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.

This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.

Provided herein are methods of treating a subject that include administering a therapeutically effective amount of an NLPR3 antagonist or a pharmaceutically acceptable salt, solvate, or co-crystal thereof to a subject identified as having a cell that has an elevated level of NLRP3 inflammasome activity and/or expression as compared to a reference level. Provided herein are methods of treating a subject, methods of selecting a treatment for a subject, methods of selecting a subject for treatment, and methods of selecting a subject for participation in a clinical study that include the administration of a therapeutically effective amount of an NLRP3 antagonist. Also provided are methods of treating a subject having resistance to an anti-TNFα agent and methods of determining the efficacy of treatment with an anti-TNFα agent. Also provided are methods of treating a subject with a combination of an NLRP3 antagonist and an anti-TNFα agent.

The invention relates to the treatment of brain tumors, specifically to improved therapy for glioblastoma utilizing specific endocrine modulators and drug combinations. The compositions and uses thereof according to the invention employ androgen receptor (AR) inhibitors, either alone or in combination with receptor tyrosine kinase inhibitors and/or chemotherapeutic agents. According to certain advantageous embodiments, the use of the AR inhibitor enzalutamide, optionally in combination with epidermal growth factor receptor inhibitors such as erlotinib and alkylating agents such as carmustine and temozolomide, is contemplated.

The invention relates to the treatment of brain tumors, specifically to improved therapy for glioblastoma utilizing specific endocrine modulators and drug combinations. The compositions and uses thereof according to the invention employ androgen receptor (AR) inhibitors, either alone or in combination with receptor tyrosine kinase inhibitors and/or chemotherapeutic agents. According to certain advantageous embodiments, the use of the AR inhibitor enzalutamide, optionally in combination with epidermal growth factor receptor inhibitors such as erlotinib and alkylating agents such as carmustine and temozolomide, is contemplated.

The invention relates to the treatment of brain tumors, specifically to improved therapy for glioblastoma utilizing specific endocrine modulators and drug combinations. The compositions and uses thereof according to the invention employ androgen receptor (AR) inhibitors, either alone or in combination with receptor tyrosine kinase inhibitors and/or chemotherapeutic agents. According to certain advantageous embodiments, the use of the AR inhibitor enzalutamide, optionally in combination with epidermal growth factor receptor inhibitors such as erlotinib and alkylating agents such as carmustine and temozolomide, is contemplated.

The present disclosure features compositions and methods for the treatment of bacterial infections, such as bacterial infections caused by bacterial cells residing within a host cell (e.g., a mammalian cell, e.g., immune cell, e.g., macrophage or dendritic cell). The compositions and methods include delivering antimicrobial agents to specifically target the intracellular compartment (endosome, phagosome, lysosome, or cytosol) in which the bacterial cell resides.

The present disclosure features compositions and methods for the treatment of bacterial infections, such as bacterial infections caused by bacterial cells residing within a host cell (e.g., a mammalian cell, e.g., immune cell, e.g., macrophage or dendritic cell). The compositions and methods include delivering antimicrobial agents to specifically target the intracellular compartment (endosome, phagosome, lysosome, or cytosol) in which the bacterial cell resides.

The present disclosure describes the use of 2,4-disulfonyl phenyl tert-butyl nitron (2,4-ds-PBN) in the treatment of temozolomide drug resistant gliomas. The 2,4-ds-PBN may be used combined with other chemo- and radiotherapies and surgery, including temozolomide, to reduce glioma occurrence, recurrence, spread, growth, metastasis, and vascularization, and to inhibit development of temozolomide resistance.

The present disclosure describes the use of 2,4-disulfonyl phenyl tert-butyl nitron (2,4-ds-PBN) in the treatment of temozolomide drug resistant gliomas. The 2,4-ds-PBN may be used combined with other chemo- and radiotherapies and surgery, including temozolomide, to reduce glioma occurrence, recurrence, spread, growth, metastasis, and vascularization, and to inhibit development of temozolomide resistance.