The androgen receptor-targeted proteolysis targeting chimera and other alternative therapeutic choices in overcoming the resistance to androgen deprivation treatment in prostate cancer.

Androgen receptor (AR) plays a vital role in prostate cancer (PCa), including castration-resistant PCa, by retaining AR signalling. Androgen deprivation treatment (ADT) has been the standard treatment in the past decades. A great number of AR antagonists initially had been found effective in tumour remission; however, most PCa relapsed that caused by pre-translational resistance such as AR mutations to turn antagonist into agonist, and AR variants to bypass the androgen binding. Recently, several alternative therapeutic choices have been proposed. Among them, proteolysis targeting chimera (PROTAC) acts different from traditional drugs that usually function as inhibitors or antagonists, and it degrades oncogenic protein and does not disrupt the transcription of an oncogene. This review first discussed some essential mechanisms of ADT resistance, and then introduced the application of AR-targeted PROTAC in PCa cells, as well as other AR-targeted therapeutic choices.

[Effects of honey to acyclovir in the rabbit eye transport kinetics].

OBJECTIVE: Using pharmacokinetics to explore the mechanism of honey to enhance the efficacy of acyclovir (ACV) treatment of herpes simplex keratitis (HSK), providing the basis for combination of the prescription of two drugs and dosage regimen designed. METHOD: Single dosages of 5% honey and 0% honey Meyasu eye ointment are injected into rabbit eyes. The aqueous humor of rabbit eye is measured at different times, specifically the content of ACV in aqueous humor by HPLC. Mathematical models are established, from which pharmacokinetic parameters are extracted and compared by mathematics and statistics methods. RESULT: Both the 5% and 0% honey Meyasu eye ointment in rabbit eyes are belong to a two-compartment model. The absorption half-life of the 5% Meyasu eye ointment in aqueous humor is as 2.30 times longer, the distribution half-life is 2.12 times longer, the peak concentration is 1.17 times longer, the peak time is 1.36 times longer, AUC is 1.41 times longer when compared to the 0% Meyasu eye ointment. CONCLUSION: Honey can significantly increase the ACV concentration and bioavailability in the eye, extend the action time of ACV in target cells and increase the retention capacity of ACV in the target tissue; thereby improving treatment success.