Increased understanding of molecular pathways leads to the development of effective targeted therapies for the treatment of solid tumors. Dabrafenib (DAB) undergoes oxidative metabolism via cytochrome P450 (CYP) 3A4 and CYP2C8 to form hydroxy-dabrafenib (OHD), an active metabolite, with a twofold higher potency than an inhibitor of mutant BRAF. OHD (purity>99 %) was synthesized by Medicilon. Medicilon synthetic chemistry team is capable of the independent design of synthesis pathways and complex compound treatments, key to helping accelerate drug discovery.

Radiation therapy is used as the primary treatment for lung cancer. In this study, radiation therapy for establish ionizing radiation-resistant lung cancer cell lines (A549-IR/H1299-IR) was supported by Medicilon. The A549 and H1299 cells in exponential growth phase were treated with a repeated IR dose of 2 Gy each at room temperature and then returned to the incubator.

Chimeric antigen receptor T cells (CAR-T) immunotherapy has shown promising clinical results in the treatment of leukemia and lymphoma, but the effectiveness is limited for solid tumors. The shRNA vector plasmid that silences PD-1 and preparation of CAR is constructed. The plasmids sequenced were fully identified by Medicilon.

An amorphous solid dispersion (ASD) of Sorafenib (SOR) was used to develop an immediate release tablet with improved oral bioavailability. The SOR ASD tablets exhibited approximately 50% higher relative bioavailability in dogs than the marketed SOR tablet product, Nexavar®. The pharmacokinetic (PK) study of SOR ASD tablets and Nexavar® tablets was performed by Medicilon.

Cell division cycle 7 (CDC7), a serine/threonine kinase, plays important roles in the initiation of DNA replication. TAK-931, a highly specific CDC7 inhibitor, exhibits antitumor efficacy and immunity. The flowcytometry-based immune profiling panel studies in J558 allograft syngeneic mouse models were performed at Medicilon. In vivo efficacy studies in J558 allograft models in combination with anti-mPD-1, anti-mPD-L1, and anti-mCTLA-4 antibodies were performed at Medicilon.

​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.