The present invention relates to compounds of Formula (I) that target the MLH1 and/or PMS2 proteins that are components of the DNA Mismatch Repair (MMR) process:

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wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.6 and R.sup.10 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which MLH1 and/or PMS2 activity is implicated.

The present invention relates to compounds of Formula (I) that target the MLH1 and/or PMS2 proteins that are components of the DNA Mismatch Repair (MMR) process:

##STR00001##

wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.6 and R.sup.10 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which MLH1 and/or PMS2 activity is implicated.

The present disclosure provides, inter alia, compounds to modulate GPX4 activity. Also provided are pharmaceutical compositions containing same compounds. Further provided are methods for treating or ameliorating the effects of a cancer in a subject, methods of modulating GPX activity in a subject, methods of inducing ferroptosis in a cell, and methods for treating or ameliorating the effects of a cancer in a subject using the compounds or composition in combination with other therapeutic agents.

The present disclosure provides, inter alia, compounds to modulate GPX4 activity. Also provided are pharmaceutical compositions containing same compounds. Further provided are methods for treating or ameliorating the effects of a cancer in a subject, methods of modulating GPX activity in a subject, methods of inducing ferroptosis in a cell, and methods for treating or ameliorating the effects of a cancer in a subject using the compounds or composition in combination with other therapeutic agents.

Provided herein are small molecule Epstein-Barr virus-induced G-protein coupled receptor 2 (EBI2) modulator compounds, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds. EBI2 is a therapeutic target for the treatment of a variety of diseases or conditions. In some embodiments, EBI2 is a therapeutic target for the treatment of diseases or conditions such as, but not limited to, autoimmune diseases or conditions, cancer, and cardiovascular disease.

Provided herein are small molecule Epstein-Barr virus-induced G-protein coupled receptor 2 (EBI2) modulator compounds, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds. EBI2 is a therapeutic target for the treatment of a variety of diseases or conditions. In some embodiments, EBI2 is a therapeutic target for the treatment of diseases or conditions such as, but not limited to, autoimmune diseases or conditions, cancer, and cardiovascular disease.

The eyewear material is an eyewear material containing thermoplastic polyurethane. The eyewear material has a tan δ peak at both less than 0° C. and 0° C. or more and 70° C. or less observed in dynamic viscoelasticity measurement in tensile mode under the measurement conditions of a temperature increase speed of 5° C./min and a measurement frequency of 10 Hz.

The eyewear material is an eyewear material containing thermoplastic polyurethane. The eyewear material has a tan δ peak at both less than 0° C. and 0° C. or more and 70° C. or less observed in dynamic viscoelasticity measurement in tensile mode under the measurement conditions of a temperature increase speed of 5° C./min and a measurement frequency of 10 Hz.

The invention provides a compound of Formula I, an isomer, a pharmaceutically acceptable salt, or a solvate thereof, and use thereof in manufacture of a medicament for preventing and/or treating a drug-resistant tumor or disease or disorder caused by a drug-resistant bacterium, or use thereof in manufacture of a medicament for preventing and/or treating a tumor, a neurodegenerative disease, an allogeneic graft rejection, or an infection-associated disease or disorder; preferably, the tumor, neurodegenerative disease, allogeneic graft rejection, or infection-associated disease or disorder is a disease or disorder caused by Heat shock protein 70 (Hsp70). The compounds of the invention, which are a class of Hsp70 inhibitors having a novel structure and a high activity, solve the problem concerning drug resistance of tumors, enhance the effect of treating tumors, and provide a new medical strategy for treatment of tumors in clinic. ##STR00001##

The invention provides a compound of Formula I, an isomer, a pharmaceutically acceptable salt, or a solvate thereof, and use thereof in manufacture of a medicament for preventing and/or treating a drug-resistant tumor or disease or disorder caused by a drug-resistant bacterium, or use thereof in manufacture of a medicament for preventing and/or treating a tumor, a neurodegenerative disease, an allogeneic graft rejection, or an infection-associated disease or disorder; preferably, the tumor, neurodegenerative disease, allogeneic graft rejection, or infection-associated disease or disorder is a disease or disorder caused by Heat shock protein 70 (Hsp70). The compounds of the invention, which are a class of Hsp70 inhibitors having a novel structure and a high activity, solve the problem concerning drug resistance of tumors, enhance the effect of treating tumors, and provide a new medical strategy for treatment of tumors in clinic. ##STR00001##