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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.

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.

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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 TR¦Â 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.

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.

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).

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.

Aberrant activation of the PI3K pathway has been intensively targeted for cancer therapeutics for decades. In this work, researchers designed and synthesized a novel photocaged PI3K inhibitor 1, which could be readily activated by UV irradiation to release a highly potent PI3K inhibitor 2. ADME studies of compounds 1 and 2 were conducted by Medicilon. Medicilon's pharmacokinetics department offers the clients a broad spectrum of high quality of services in the areas of in vitro ADME, in vivo pharmacokinetics and bioanalysis services, ranging from small molecules to large molecules, such as protein and antibody.

Receptor interacting protein kinase-2 (RIPK2) is an enzyme involved in the transduction of pro-inflammatory nucleotide-binding oligomerization domain cell signaling, a pathway implicated in numerous chronic inflammatory conditions. UH15-15 inhibits RIPK2 kinase (IC50=8 nM) and demonstrates favorable in vitro ADME and pharmacokinetic properties. The pharmacokinetic study was conducted by Medicilon.

PD-1 and PD-L1 have been very successful for the treatment of various tumors, including NSCLC, urothelial cancer, melanoma, head and neck squamous cell cancer, and lymphoma. Researchers identified compound L7 as a potent PD-L1 inhibitor that blocked PD-1/PD-L1 interaction. Pharmacokinetic (PK) studies demonstrated that L7 was orally bioavailable. PK studies were conducted by Medicilon.