Provided are compounds of Formula (I): (I) and pharmaceutically acceptable salts and compositions thereof, which are useful for treating a variety of conditions associated with TREX1.

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Provided are compounds of Formula (I): (I) and pharmaceutically acceptable salts and compositions thereof, which are useful for treating a variety of conditions associated with TREX1.

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The present application is directed to a method of inhibiting proliferation of chromosome instable cancer cells. This method involves administering, to a population of cancer cells comprising chromosome instable cancer cells, an inhibitor of Kinesin Family Member 18A (KIF18A) at a dosage effective to inhibit proliferation of said chromosome instable cancer cells. The inhibitors of KIF18A may also be used in a method treating cancer in a subject. This method involves selecting a subject having cancer, where the cancer is characterized by chromosomal instability, and administering to the subject an inhibitor of KIF18A at a dosage effective to treat the cancer in the subject. Also disclosed is a combination therapeutic including an inhibitor of Kinesin Family Member 18A (KIF18A) and agent that promotes microtubule turnover or a cyclin-dependent kinase (CDK) inhibitor.

The present application is directed to a method of inhibiting proliferation of chromosome instable cancer cells. This method involves administering, to a population of cancer cells comprising chromosome instable cancer cells, an inhibitor of Kinesin Family Member 18A (KIF18A) at a dosage effective to inhibit proliferation of said chromosome instable cancer cells. The inhibitors of KIF18A may also be used in a method treating cancer in a subject. This method involves selecting a subject having cancer, where the cancer is characterized by chromosomal instability, and administering to the subject an inhibitor of KIF18A at a dosage effective to treat the cancer in the subject. Also disclosed is a combination therapeutic including an inhibitor of Kinesin Family Member 18A (KIF18A) and agent that promotes microtubule turnover or a cyclin-dependent kinase (CDK) inhibitor.

The present invention relates to the technical field of medicines. Specifically disclosed is a compound as represented by formula I′, or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof, symbols therein being as defined in the claims. The compound of the present invention may be used as a drug for regulating RET kinase activity or treating RET-related diseases, and has good pharmacokinetic properties.

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Provided herein are methods of treating cartilage disorders in a subject using a dual CLK/DYRK inhibitor, or a pharmaceutically acceptable salt of solvate thereof, or a combination of a CLK inhibitor, or a pharmaceutically acceptable salt of solvate thereof, and DYRK inhibitor or, pharmaceutically acceptable salt or solvate thereof.

Provided herein are methods of treating cartilage disorders in a subject using a dual CLK/DYRK inhibitor, or a pharmaceutically acceptable salt of solvate thereof, or a combination of a CLK inhibitor, or a pharmaceutically acceptable salt of solvate thereof, and DYRK inhibitor or, pharmaceutically acceptable salt or solvate thereof.

Provided herein are compositions and methods of use thereof for the treatment of fungal infections and diseases.

Provided herein are compositions and methods of use thereof for the treatment of fungal infections and diseases.

The present disclosure generally relates to a method of improving cognition and/or treating cognitive decline in a cognitively healthy subject comprising administering to the cognitively healthy subject a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt, solvate or prodrug thereof, as described herein.