南宫NG·28

Pan-bromodomain and extra terminal (Pan-BET) inhibitors show profound efficacy but exhibit pharmacology-driven toxicities in clinical trials. The representative Compound 8l (XY153), a novel BD2-selective BET inhibitor, potently binds to BRD4 BD2 with an IC50 value of 0.79 nM. XY153 displayed potent antiproliferative activity against multiple tumor cell lines. XY153 also demonstrated good metabolic stability in vitro. These data indicate that XY153 may serve as a new and valuable lead compound for the development of potential therapeutics against acute myeloid leukemia (AML). All liver microsome assays were performed by Medicilon.

Y180, an orally available Mpro inhibitor, is effective against wild-type SARS-CoV-2 and variants. Y180 displayed satisfying PK properties in mice, rats and dogs, with oral bioavailabilities of 92.9%, 31.9% and 85.7%, respectively. The in vivo PK properties of Y180 were evaluated. All procedures related to animal handling, care and treatment in PK studies were performed according to approved guidelines. The PK studies were approved by the Ethics Committee of Medicilon.

Ulotaront (SEP-363856) is a TAAR1 agonist with 5-HT1A agonist activity currently in clinical development for the treatment of Schizophrenia. Ulotaront exhibits rapid absorption, greater than 70% bioavailability, and good penetration across the blood–brain barrier in preclinical species. The distribution of Ulotaront to rat brain was conducted at Medicilon/MPI Preclinical Research. Ulotaront monkey plasma PK was conducted at Medicilon/MPI Preclinical Research.

Biofouling poses one of the most serious problems to marine industry and aquaculture development. Five structurally similar compounds were isolated from the crude extract of a marine Streptomyces strain. Antifouling activities of these compounds and four other structurally-related compounds isolated from another marine Streptomyces species were compared to generate structure–activity relationship data. Based on structure–activity relationship analysis, another compound with a simplified structure but excellent antifouling activities was synthesized. The optimized compound was synthesized by Medicilon.

Nobiliside A, a new triterpene glycoside, exhibits some biological activities including antifungal and cytotoxic effects. A LC/MS/MS method was developed and validated for determination of Nobiliside A in rat plasma, would prove to be useful for other pharmacokinetic assessments. Male SD rats were housed in Medicilon animal facility. The animal experiments of the present study were approved by IACUC of Medicilon and were carried out in accordance with the SOPs of the facility.

4-n-butyl resorcinol (4-nBR) is a highly effective tyrosinase inhibitor, and can be used in cosmetic product for depigmentation purpose. Its efficacy correlates with 4-nBR that absorbed by skin. In this study, skin distribution of 4-nBR within either human or pig skin ex vivo was studied and compared by three independent laboratories. Good agreement was observed in each compartment considering usual inter-lab variability. The percutaneous absorption and skin distribution studies were carried out by L'Oréal (lab A), Fudan University (lab B), and Medicilon (lab C).

Columbin is an important component isolated from Radix Tinosporae. Columbin possesses many pharmacological activities, including anti-inflammation, and antitumor activity in vivo. The purpose of the present study was to examine in vivo pharmacokinetics and bioavailability of Columbin in rats using a high-performance liquid chromatography coupled with tandem mass spectrometry quantitative detection method. This is the first study demonstrating the bioanalytical method and pharmacokinetic of Columbin. Animal studies were carried out in Medicilon.

Paclitaxel-loaded hyaluronan solid nanoemulsions (PTX-HSNs) were successfully fabricated for the delivery of PTX to improve ovarian cancer treatment via active tumor targeting. The in vivo toxicity, in vivo antitumor effects, and pharmacokinetics of PTX-HSNs and Taxol were evaluated in nude mice and rats. PTX-HSN is a highly effective nanosystem with a high maximum tolerated dose (MTD) for delivering PTX to ovarian cancers characterized by CD44 overexpression, enhanced active tumor targeting, and low toxicity. All in vivo experiments were conducted with the approval of the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International (tested at Medicilon/MPI Preclinical Research).

A simple and accurate liquid chromatography coupled with tandem mass spectrometry method was developed for determination and in vivo pharmacokinetic studies of vitexin rhamnoside in rat plasma. Practical utility of this new LC/MS/MS method was confirmed in pilot pharmacokinetic studies in rats following both intravenous and oral administration. Animal studies were carried out in Medicilon.

Liver cancer is the fourth greatest cause of cancer related mortality. AD80 is a multi-kinase inhibitor with anti-tumoral activity across a variety of hepatocellular carcinoma (HCC) preclinical models, including mouse xenografts. AD80 is highly active in a tumor xenograft model. Experimental dosing for AD80 was determined from maximum tolerated dosage (MTD) studies and pharmacokinetic (PK) analysis. Quantities of AD80 in blood plasma were determined by LC-MS/MS at Medicilon.