Abstract: This document relates to methods and materials for assessing biological aging. For example, methods and materials that can be used to determine if a mammal (e.g., a human) has an advanced biological age, is at risk of developing one or more adverse outcomes (e.g., adverse outcomes associated with medical intervention at an advanced biological age) following a medical intervention, and/or is likely to be responsive to one or more senotherapeutic agents are provided herein. In some cases, methods and materials for using one or more senotherapeutic agents to improve one or more outcomes for a mammal following a medical intervention (e.g., surgery) are also provided.

Abstract: This document relates to methods and materials for assessing biological aging. For example, methods and materials that can be used to determine if a mammal (e.g., a human) has an advanced biological age, is at risk of developing one or more adverse outcomes (e.g., adverse outcomes associated with medical intervention at an advanced biological age) following a medical intervention, and/or is likely to be responsive to one or more senotherapeutic agents are provided herein. In some cases, methods and materials for using one or more senotherapeutic agents to improve one or more outcomes for a mammal following a medical intervention (e.g., surgery) are also provided.

Described herein are Mpro cysteine protease inhibitors and methods of utilizing such inhibitors in the treatment of diseases, disorders, or conditions. Also described herein are pharmaceutical compositions containing such compounds.

Described herein are Mpro cysteine protease inhibitors and methods of utilizing such inhibitors in the treatment of diseases, disorders, or conditions. Also described herein are pharmaceutical compositions containing such compounds.

Disclosed are methods of treating cancer comprising administering to a subject in need thereof an effective amount of (3R)-4-[2-[4-[1-(3-Methoxy-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-4-piperidyl]phenoxy]ethyl]-1,3-dimethyl-piperazin-2-one or a pharmaceutically acceptable salt thereof and an effective amount of venetoclax or a pharmaceutically acceptable salt thereof.

Disclosed are methods of treating cancer comprising administering to a subject in need thereof an effective amount of (3R)-4-[2-[4-[1-(3-Methoxy-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-4-piperidyl]phenoxy]ethyl]-1,3-dimethyl-piperazin-2-one or a pharmaceutically acceptable salt thereof and an effective amount of venetoclax or a pharmaceutically acceptable salt thereof.

Disclosed are methods of treating cancer comprising administering to a subject in need thereof an effective amount of (3R)-4-[2-[4-[1-(3-Methoxy-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-4-piperidyl]phenoxy]ethyl]-1,3-dimethyl-piperazin-2-one or a pharmaceutically acceptable salt thereof and an effective amount of venetoclax or a pharmaceutically acceptable salt thereof.

Embodiments of the disclosure encompass methods and compositions related to overcoming or preventing cancer resistance to anti-apoptotic proteins, for example BH3 mimetics. The disclosure provides methods for modulating p73 to reduce cancer resistance to BH3 mimetics including inhibitors of Bcl-2, Bcl-xL, Mcl-1, Bcl-W, A1/BFL-1, or a combination thereof. In specific embodiments, targeting isoforms of p73, such as TAp73 or DNp73, results in reduction of cancer resistance to BH3 mimetics to allow effective treatment of hematological cancers.

Embodiments of the disclosure encompass methods and compositions related to overcoming or preventing cancer resistance to anti-apoptotic proteins, for example BH3 mimetics. The disclosure provides methods for modulating p73 to reduce cancer resistance to BH3 mimetics including inhibitors of Bcl-2, Bcl-xL, Mcl-1, Bcl-W, A1/BFL-1, or a combination thereof. In specific embodiments, targeting isoforms of p73, such as TAp73 or DNp73, results in reduction of cancer resistance to BH3 mimetics to allow effective treatment of hematological cancers.

Embodiments of the disclosure encompass methods and compositions related to overcoming or preventing cancer resistance to anti-apoptotic proteins, for example BH3 mimetics. The disclosure provides methods for modulating p73 to reduce cancer resistance to BH3 mimetics including inhibitors of Bcl-2, Bcl-xL, Mcl-1, Bcl-W, A1/BFL-1, or a combination thereof. In specific embodiments, targeting isoforms of p73, such as TAp73 or DNp73, results in reduction of cancer resistance to BH3 mimetics to allow effective treatment of hematological cancers.