Jul 06,2023

PDE1是與中樞和外周疾病密切相關的藥物靶點，研究人員合成一種PDE1 抑制劑在大鼠肝微粒體中具有良好的代謝穩定性。其中穩定性測試通過尊龍凱時進行

Phosphodiesterase-1 (PDE1) is a promising drug target closely related to central and peripheral diseases. Compound 2j with the IC50 of 21 nM against PDE1B, shows good metabolic stability in the rat liver microsomes. Stability test in the rat liver microsomes were performed by Medicilon.

Jul 06,2023

SKLB-YTH-60可改善博來霉素誘導的肺纖維化小鼠模型中的炎癥和纖維化，YTH-60的體內藥代動力學研究通過尊龍凱時進行

Idiopathic pulmonary fibrosis is a chronic and lethal lung disease associated with fibroblast activation, myoblast proliferation and extracellular matrix deposition. SKLB-YTH-60 was developed through computer-aided drug design, de novo synthesis and high-throughput screening. YTH-60 has obvious anti‐proliferative activity on fibroblasts and A549 cells. YTH-60 has an acceptable oral bioavailability and appropriate eliminated half-life time. The in vivo pharmacokinetic study of YTH‐60 was performed by Medicilon.

Jul 06,2023

研究人員成功發現了一種口服PROTAC降解劑SIAIS164018，具有良好的體內耐受性。PK和MTD研究通過尊龍凱時進行

PROTAC is an attractive technology in drug discovery. Researchers successfully discovered an orally available PROTAC degrader SIAIS164018 which degrades not only ALK or mutant EGFR but also oncoproteins involved in metastasis. SIAIS164018 is orally bioavailable and well tolerated in vivo. Pharmacokinetic and maximal tolerated dose (MTD) assays were performed by Medicilon.

Jul 06,2023

開發具有口服活性的高度選擇性卵泡刺激激素受體激動劑，且進行臨床前研究。其中對大鼠和狗的毒理學評估通過尊龍凱時進行

TOP5300 is an orally active follicle stimulating hormone receptor allosteric agonist that provides a preferred treatment for over 16 million infertile women of reproductive age in low complexity methods or in high complexity methods. TOP5300 was evaluated in standard ADME, including Cytochrome P450 inhibition, clearance and pharmacokinetic profiles. Toxicological evaluations were performed in both rat and dog as the second species according to the guidance from FDA. These assays were performed by Medicilon.

Jul 06,2023

PARP1/2抑制劑有治療腫瘤的潛力，PARP1/2抑制實驗通過尊龍凱時進行

Poly ADP-ribose polymerases (PARPs) are a family of enzymes related to DNA damage repair process. Inhibition of PARP1/2 accelerates the damage of injured DNA, which is synthetically lethal to DNA-repairing-deficient cancer cells, such as BRCA1/2-deficient cells. PARP1/2 inhibitors could be a promising candidate for the treatment of cancer. The PARP1 and PARP2 inhibition assays were performed by Medicilon.

Jul 06,2023

使用尊龍凱時硒代氨基酸培養基產品發表的學術文獻

尊龍凱時提供全套M9硒代蛋氨酸（SeMET）培養基，可用于IPTG誘導的大腸桿菌表達系統，生產硒代蛋氨酸標記的蛋白，運用多波長反常散射（MAD）方法進行蛋白質晶體學研究。

Jul 05,2023

設計合成一種高度選擇性的H435R突變敏感的甲狀腺激素受體β激動劑，PK分析通過尊龍凱時進行

Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that belong to the nuclear receptor superfamily and also participate in important physiological functions. In this study, Compound 16g is a well-characterized selective and mutation-sensitive TRβ agonist for further investigating its function in treating dyslipidemia, nonalcoholic steatohepatitis (NASH), and resistance to thyroid hormone (RTH). Compound 16g showed excellent lipid metabolism, safety, metabolic stability, and pharmacokinetic properties. PK properties of Compound 16g were analyzed by Medicilon.

Jul 05,2023

研究人員設計合成STAT3和HDAC雙通路抑制劑用于治療實體腫瘤，PK實驗通過尊龍凱時進行

The inhibition of HDACs will lead to compensated activation of a notorious cancer-related drug target, STAT3, in breast cancer through a cascade, which probably limits the anti-proliferation effect of HDAC inhibitors in solid tumors. Herein, researchers synthesized a series of potent pterostilbene hydroxamic acid derivatives with dual-target inhibition activity. The pharmacokinetic experiment in SD Rats was carried out by Medicilon.

Jul 05,2023

阿帕替尼通過VEGFR2通路抑制紫杉醇對胃癌細胞的耐藥性

Overexpression of VEGFR2 can offset the rescue effect of Apatinib on Paclitaxel-induced drug resistance of MGC803 cells. Apatinib inhibits Paclitaxel resistance of MGC803 cells via the VEGFR2 signaling pathway. In this research, the VEGFR2 sequences were designed and then amplified by RT-PCR. The sequences were then ligated with a pcDNA3.0 plasmid to construct a recombinant pcDNA3.0-VEGFR2 vector (Medicilon).

Jul 05,2023

研究人員報告了一種具有細胞滲透性的選擇性METTL3納摩爾抑制劑UZH1a，作者感謝尊龍凱時合成了UZH1a和UZH1b

The methylase METTL3 is the writer enzyme of the N6‐methyladenosine (m6A) modification of RNA. Here researchers report a nanomolar inhibitor of METTL3 (UZH1a) which is selective and cell‐permeable, while its enantiomer UZH1b is essentially inactive. The authors thank Medicilon for the synthesis of the UZH1a and UZH1b compounds.