The present disclosure is generally directed to profiling peptides, compositions, and kits, as well as methods of use thereof. The profiling peptides comprise an Mcl-1 binding domain, and optionally a cellular uptake moiety. The methods of using such profiling peptides include predicting sensitivity of a cancer, selecting a treatment, treating a cancer, producing a sensitivity profile, and the like.

The present disclosure is directed to adenine analogs, methods of making adenine analogs, and methods of treating disorders associated with PINK1 kinase activity including, but not limited to, neurodegenerative diseases, mitochondrial diseases, fibrosis, and/or cardiomyopathy using these analogs. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

The present disclosure provides diagnostic methods useful for predicting a patient's response to alvocidib and guiding a physician decision to administer alvocidib to the patient.

The present invention provides methods of predicting cell sensitivity or resistance to a therapeutic agent.

Mitochondria-targeting potassium sensors and method(s) for making such sensors. The sensor shows a response to potassium and displays a 130-fold dynamic range of fluorescence intensity and high brightness. The sensors response to potassium concentrations was demonstrated to be unaffected by cellular pH value and/or concentrations of other ions. The sensors can be used for monitoring the mitochondrial potassium efflux/influx.

The present invention concerns machine learning based methods and systems for diagnosing and treating genetic diseases characterized by mitochondrial dysfunctions. A library of reference learning models is developed based on in vitro reference samples obtained from cell-cultures exposed to specific mitochondrial inhibitors. Each model is able to predict a specific labeled mitochondrial dysfunction induced in the cell-culture by the inhibitor/stressor. The reference models are then applied to target samples drawn in vivo from target subjects who are known to have specific genetic mitochondrial diseases. A mapping is developed between mitochondrial dysfunctions predicted in the subjects and their known mitochondrial diseases. This mapping and the reference models are then applied to a clinical sample of an undiagnosed patient in whom a diagnosis of a mitochondrial dysfunction and an associated mitochondrial disease is made. If there is a known rescuer for the mitochondrial dysfunction, it may be recommended in a personalized, targeted therapy.

The present invention encompasses the use of compounds for a novel approach to treat and prevent diseases, conditions, and disorders such as diabetes and ischemic reperfusion injury. Compounds of the invention, including but not limited to BAM15 ((2-fluorophenyl){6-[(2-fluorophenyl)amino](1,2,5-oxadiazolo[3,4-e]pyrazin-5-yl)}amine), a mitochondrial uncoupler, can improve glucose tolerance, increases cellular oxygen consumption, treat or prevent kidney ischemia reperfusion injury reverse insulin resistance, reverse or treat hyperinsulinemia, and reverse or treat hyperlipidemia. The present invention further provides novel compounds as well as methods for identifying compounds with the same or similar properties as BAM15.

The present invention relates to a reporter for measuring OMA1 protease activity comprising a targeting sequence and a signal producing domain, wherein the targeting sequence is also the sequence recognized by OMA1.

The invention relates generally to systems and methods of bioenergetic profiling, uses thereof, and systems and devices relating thereto. In particular, methods of the invention are useful in assessing wellness, particularly in elderly subjects. Described are systems and methods of assessing likelihood of subject morbidity, life expectancy, positive clinical outcome, responsiveness to treatment, and certain disease states as well as of selecting treatment strategy, improving outcome to treatment strategy, and treating subjects with low bioenergetic profiles. Also described are devices and systems for measuring respiratory capacity.

The present invention encompasses the use of compounds for a novel approach to treat and prevent diseases, conditions, and disorders such as diabetes and ischemic reperfusion injury. Compounds of the invention, including but not limited to BAM15 ((2-fluorophenyl){6-[(2-fluorophenyl)amino](1,2,5-oxadiazolo[3,4-e]pyrazin-5-yl)}amine), a mitochondrial uncoupler, can improve glucose tolerance, increases cellular oxygen consumption, treat or prevent kidney ischemia reperfusion injury reverse insulin resistance, reverse or treat hyperinsulinemia, and reverse or treat hyperlipidemia. The present invention further provides novel compounds as well as methods for identifying compounds with the same or similar properties as BAM15.