Traditional small molecule drugs treat diseases by binding to target proteins and subsequently modulating their functions. Inhibition of protein function can be achieved at the gene level (DNA editing), transcriptional level (siRNA and ASO), and protein level (inhibitors and TPDs). Proteolysis targeting chimera (PROTAC) technology applies bifunctional small molecules to the targeted proteins with degradation (TPD), and this technology has been considered to be revolutionary in biopharmaceuticals since it has the potential of targeting non-druggable targets and solving the resistance issue of small molecule drugs. Since its inception in 2001, PROTAC technology has been widely utilized in academia and industry. Due to the relatively large molecular weight and other issues, addressing the oral bioavailability and stability of this type of compounds has been a challenge for PROTAC drug development. Hinova has been building a PROTAC technology platform since 2016, and has developed a few PROTAC projects against multiple targets. Currently an androgen receptor (AR) PROTAC molecules is in Phase-I clinical trials.
The study of deuterated N-methyl hydrogen on the inhibition of morphine enzyme oxidation in 1961 has drawn great interests of the pharmaceutical industry ever since.
Since the breaking of carbon-hydrogen bonds is a common feature in drug metabolism, and the breaking of carbon-deuterium bonds is more difficult. The slower metabolic rate of deuterated compounds can increase the half-life or/and exposure of the active drug, and it has the potential of reducing the dosing frequency or dosage. Another advantage is that this substitution can also reduce toxicity by reducing the formation of toxic metabolites.
The FDA and NMPA have approved the first deuterated drug, AUSTEDO® (deutetrabenazine), for the treatment of Huntington's chorea. HC-1119, the first deuterium-generation drug for prostate cancer manufactured by Hinova, has entered Phase-III clinical studies in Hinova.