A61K31/33

METHODS FOR PREDICTING AND TREATING CARDIAC DYSFUNCTION
20220268782 · 2022-08-25 ·

Ageing myocardium undergoes structural and functional changes characterized by progressive cardiomyocyte hypertrophy, interstitial fibrosis and inflammation ultimately leading to diastolic and systolic dysfunction. Whilst most focus has been placed on established risk factors such as dyslipidaemia, hypertension and obesity in accelerating cardiac ageing, a potential role for amino acids has received little attention. Here the inventors show that increased phenylalanine (PA) levels induced in vitro cytosolic oxidative stress and senescence whilst in vivo led to senile-like cardiac deterioration in young mice. Moreover, they demonstrated that hepatic PA catabolism declined with age in a p21-dependent manner, whilst p21 deficiency prevented age-related cardiac dysfunction. Finally, the inventors found that Pah cofactor BH4 reversed the age-related rise in plasma PA levels and senile cardiac alterations. These observations have immediate implications for promoting cardiac health and healthspan and suggest that phenylalanine can be used as a biomarker and biotarget of cardiac dysfunction.

Treatment of hippo pathway mutant tumors and methods of identifying subjects as candidates for treatment

The present invention relates to a method of treating a tumor in a subject. This method involves administering to a subject having a Hippo pathway mutant tumor a tankyrase inhibitor, where the tumor is susceptible to treatment with the tankyrase inhibitor, and said administering is carried out to treat the tumor. The present invention also relates to a method of treating cancer in a subject, and a method of identifying a subject as a candidate for treatment.

Treatment of hippo pathway mutant tumors and methods of identifying subjects as candidates for treatment

The present invention relates to a method of treating a tumor in a subject. This method involves administering to a subject having a Hippo pathway mutant tumor a tankyrase inhibitor, where the tumor is susceptible to treatment with the tankyrase inhibitor, and said administering is carried out to treat the tumor. The present invention also relates to a method of treating cancer in a subject, and a method of identifying a subject as a candidate for treatment.

Arginase Inhibitors and Their Therapeutic Applications

Disclosed are small molecule therapeutic compounds that are potent inhibitors of arginase 1 and arginase 2 activity. Also disclosed are pharmaceutical compositions comprising the compounds, and methods for using the compounds for treating or preventing a disease or condition associated with arginase activity.

Arginase Inhibitors and Their Therapeutic Applications

Disclosed are small molecule therapeutic compounds that are potent inhibitors of arginase 1 and arginase 2 activity. Also disclosed are pharmaceutical compositions comprising the compounds, and methods for using the compounds for treating or preventing a disease or condition associated with arginase activity.

HETEROAROMATIC CHALCONE DERIVATIVES AND THEIR MEDICAL USE

The present invention relates to heteroaromatic chalcone derivatives, particularly the compounds of formula (I) as described and defined herein, pharmaceutical compositions comprising these compounds, and their medical use, including their use in the treatment or prevention of cancer and, in particular, in the treatment or prevention of hematologic malignancies.

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HETEROAROMATIC CHALCONE DERIVATIVES AND THEIR MEDICAL USE

The present invention relates to heteroaromatic chalcone derivatives, particularly the compounds of formula (I) as described and defined herein, pharmaceutical compositions comprising these compounds, and their medical use, including their use in the treatment or prevention of cancer and, in particular, in the treatment or prevention of hematologic malignancies.

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SELENOSUGARS AND THERAPEUTIC USES THEREOF

A topical composition for skin repair comprising selenosugars of formula (1): (Formula (I)) wherein, n is 1, 2 or 3; m is 2, 3, 4; or 5; and each R1 is independently-(optionally substituted C.sub.1-C.sub.3 alkyiene)p-OH, where p is 0 or 1 or a pharmaceutically acceptable salt thereof.

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SELENOSUGARS AND THERAPEUTIC USES THEREOF

A topical composition for skin repair comprising selenosugars of formula (1): (Formula (I)) wherein, n is 1, 2 or 3; m is 2, 3, 4; or 5; and each R1 is independently-(optionally substituted C.sub.1-C.sub.3 alkyiene)p-OH, where p is 0 or 1 or a pharmaceutically acceptable salt thereof.

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