​Chronic Hepatitis B virus is one of the main causes of liver diseases including cirrhosis and hepatocellular carcinoma. Isonicotinic acid inhibitors of the histone lysine demethylase 5 (KDM5) with potent anti-HBV activity. GS-5801, a potent inhibitor of KDM5, has antiviral activity against HBV in a primary human hepatocytes infection model, with the cellular permeability, oral bioavailability. GS-5801 was synthesized by Medicilon.

QF-036 is an HIV-1 maturation inhibitor in preclinical development. After oral QF-036 administration to rats and monkeys, both species exhibit moderate bioavailability, and the plasma drug exposure increased in an approximately dose-proportional manner. The favourable viral inhibitory activity and pharmacokinetic properties provide critical support for QF-036 as a promising anti-HIV therapeutic candidate. The pharmacokinetic studies were performed by Medicilon.

Threonine tyrosine kinase (TTK), a dual-specificity protein kinase, acts as a core component of the spindle assembly checkpoint and plays a crucial role in accurate separation of sister chromatids during mitosis to avoid aneuploidy. TTK inhibition is an attractive wide-spectrum strategy for cancer therapy. Researchers designed and synthesized a series of pyrido[2, 3-d]pyrimidin-7(8H)-ones as new selective orally bioavailable TTK inhibitors. All the pharmacokinetic studies were carried out by Medicilon. Compounds 5o exhibits strong binding affinity to TTK with a Kd value of 0.15 nM. Compound 5o demonstrates good oral pharmacokinetic properties.

Triple‐negative breast cancer (TNBC) is the most aggressive breast cancer subtype. ClpP is a component of the ClpXP protein complex localized in the mitochondrial matrix. Modifiers of ClpP activity have demonstrated anti-cancer properties. TR-107 is a potent chemical activator of the human mitochondrial protease ClpP, with excellent potency, specificity and drug-like properties. TR‐107 shows ClpP‐dependent growth inhibition in the low nanomolar range that is equipotent to Paclitaxel in TNBC cell models. The pharmacokinetic properties of TR‐107 were compared with other known ClpP activators including ONC201 and ONC212. TR‐107 displayed excellent exposure and serum t1/2 after oral administration. Pharmacokinetic analysis were evaluated for pharmacokinetic properties in ICR mice by Medicilon.

Ataxia telangiectasia mutated and Rad3-related (ATR) kinase is an important regulator of the DNA damage response, especially in response to replication stress. SKLB-197 is a potent and highly selective ATR inhibitor with an IC50 value of 13 nM. SKLB-197, exhibits good pharmacokinetic properties, could be a promising lead compound for drug discovery targeting ATR. The pharmacokinetic (PK) studies were performed by Medicilon.

Immune checkpoint inhibition therapies have been used for multiple cancer research. H11-HLE is a tool molecule that allows the interrogation of the contribution of Fc in mediating immune checkpoint therapy. Half-life extended H11 (H11-HLE) induces potent anti-tumor efficacy in mouse syngeneic tumor models. Authors gratefully acknowledge performing in vivo studies by Medicilon Preclinical Research LLC who performed the in vivo experiments.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent forms of chronic liver diseases. Estrogen-related receptor alpha (ERRα) is a viable target for NAFLD. JND003 is a potent and selective ERRα agonist alleviating nonalcoholic fatty liver disease and insulin resistance. JND003 is orally bioavailable and exhibits high grade of distribution in liver and abdominal adipose tissues. Pharmacokinetics (PK) and Tissue Distribution Assays of JND003 were performed at Medicilon.

Psoriasis is a common immune-mediated skin disorder manifesting in abnormal skin plaques, and PDE4 is an effective target for the treatment of inflammatory diseases such as psoriasis. Researchers designed and synthesized the lead compound with high PDE4 inhibitory potency and remarkable metabolite profiles in liver microsomes. The metabolic stability on mouse, rat, and human liver microsomes was determined by Medicilon.

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. 6-Ethynyl-1H-indole derivative 55 is a potent and selective PAK4 inhibitor (Ki=10.2 nM). Compound 55 is effective in the treatment of metastatic cancer. The pharmacokinetic study of Compound 55 was carried out by Medicilon.

Targeted protein degradation (TPD) exemplified by PROTACs is an emerging strategy for next generation drug discovery. Threonine tyrosine kinase (TTK) is a dual-specific protein kinase that catalyzes phosphorylation of both serine/threonine and tyrosine residues. Researchers designed and synthesized TTK PROTACs, which demonstrated reasonable pharmacokinetic profiles. All the pharmacokinetic studies were carried out by Medicilon, according to the protocols and guidelines of the institutional care and use committee.