Jul 06,2023

FBPase是與腫瘤和2型糖尿病相關的一個有前景的靶點。化合物W8對FBPase表現出高選擇性。W8的藥代動力學研究通過尊龍凱時進行

Fructose-1,6-bisphosphatase (FBPase) is a promising target associated with cancer and type 2 diabetes. Compounds W8 and W8k exhibit high selectivity against FBPase and W8 effectively reduces blood glucose in an Institute of Cancer Research (ICR) mice model and dose-dependent inhibition of glucose production in a primary mouse hepatocyte model. The pharmacokinetic studies of W8 and its leaving group saccharin were performed by Medicilon.

Jul 06,2023

藥物發現中的挑戰之一是識別高質量的先導化合物。此研究中PK結果表明L12可作為針對PDE5的先導化合物，進一步研究和開發。L12的PK分析通過尊龍凱時進行

Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. One of the biggest challenges in drug discovery is to identify high-quality hit and lead compounds. Lead L12 had an IC50 of 8.7 nM and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil, and PK results indicate that L12 could be used as a promising lead for further development. Pharmacokinetic properties of L12 were analyzed by Medicilon.

Jul 06,2023

ANO1是一個潛在的鎮痛靶點。DFBTA是一種有效的ANO1抑制劑，具有優異的藥代動力學特性。體內PK測試通過尊龍凱時進行

Current pain management is largely limited to opioids and non-steroidal anti-inflammatory drugs. Developing new analgesic drugs remains important to address the unmet medical needs of chronic pain patients. Calcium-activated chloride channel anoctamin-1 (ANO1) is a potential analgesic target. DFBTA is a potent inhibitor with the IC50 of 24 nM. DFBTA shows very weak cytotoxicity, cardiotoxicity, and acute toxicity, as well as excellent pharmacokinetics properties with oral bioavailability >75% and little brain penetration (<1.5% brain/plasma). In vivo PK were tested by Medicilon.

Jul 06,2023

XY153是一種有潛力的先導化合物，可用于開發針對急性髓系白血病。XY153在體外具有良好的代謝穩定性。所有肝微粒體測定均通過尊龍凱時進行

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.

Jul 06,2023

Y180是一種口服Mpro抑制劑，可有效對抗野生型SARS-CoV-2及其變種。Y180在小鼠、大鼠和狗中具有良好的PK特性

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.

Jul 06,2023

Ulotaront是一種具有5-HT1A激動劑活性的TAAR1 激動劑，可用于治療精神分裂癥。Ulotaront在大鼠腦中的分布和在猴血漿中的PK研究通過尊龍凱時進行

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.

Jul 06,2023

基于構效關系分析，合成了一種結構簡化但具有優異防污活性的化合物。優化后的化合物通過尊龍凱時合成

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.

Jul 06,2023

開發和驗證大鼠血漿中Nobiliside A定量的LC/MS/MS方法

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.

Jul 06,2023

4-正丁基間苯二酚是一種高效的酪氨酸酶抑制劑，可用于化妝品中以達到脫色的目的。其中經皮吸收和皮膚分布研究通過尊龍凱時進行

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).

Jul 06,2023

Columbin具有多種藥理活性，包括體內抗炎和抗腫瘤活性，此實驗中動物研究通過尊龍凱時進行

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.