918博天堂

作为泰恩康的持久合作同伴，918博天堂依附临床前研发服务平台，为CKBA乳膏提供了幼型猪药代动力学钻延注造剂安全性评价、体内光毒性试验等钻研服务。

Biofouling is one of the most serious problems in the maritime industry and aquaculture development. In the marine environment, submerged surfaces are often colonized by marine organisms that have come to be called biofoulers, which are marine organisms that attach to submerged surfaces. Biofoulers increase the weight, drag and surface corrosion of ships, and lead to huge costs to maintain mariculture systems and seawater pipelines. Antifouling compounds are used as biocides in marine paints that are coated on the submerged surfaces to control the preponderance of biofoulers. Butenolide [5-octylfuran-2(5H)-one] is a very promising anti-marine-fouling compound. The antifouling compound 5-octylfuran-2(5H)-one (here referred to as butenolide) was synthesized by Medicilon.

Nuclear receptors are ligand-activated transcription factors involved in regulating many physiologic and pathologic processes. Ligand binding to nuclear receptors leads to dissociation of co-repressors, recruitment of co-activators, and subsequent activation of gene expression. Because of their associations with many human diseases, nuclear receptors are therapeutic targets for pharmaceutical development. The pregnane X receptor (PXR, NR1I2) belongs to the nuclear receptor family. The activity of PXR can be controlled by the binding of small molecule agonists or antagonists. Because of its unique ligand binding pocket, PXR binds promiscuously to structurally diverse chemicals. PXR regulates the expression of proteins such as drug metabolizing enzyme cytochrome P450 3A4 (CYP3A4), efflux transporter P-glycoprotein, and other multidrug resistance proteins, which are involved in metabolism and elimination of potentially harmful chemicals. PXR has been detected in various tissues including kidney, colon, brain capillaries, small intestine, and predominantly in liver, and it can be activated by various ligands that bind to its ligand binding domain (LBD). PXR forms a heterodimeric complex with RXR to activate gene transcription. The recombinant pETDuet1-hPXR-LBD/mSRC-1 plasmid (Medicilon, Shanghai, China) was transformed into Escherichia coli BL21 DE3 cells for protein expression.

SM-1200, a potent bivalent Smac mimetic, induces rapid, complete, and durable tumor regression in mice. X-linked inhibitor of apoptosis protein (XIAP) and cellular IAP1/2 (cIAP1/2) regulate apoptosis and are promising cancer therapeutic targets. Smac (second mitochondria-derived activator of caspases), also known as DIABLO, antagonizes IAP proteins. Researchers designed and synthesized new compounds based on bivalent Smac mimetics, leading to the identification of SM-1200 (compound 12). SM-1200 binds to XIAP (Ki = 0.5 nM), cIAP1 (Ki = 3.7 nM), and cIAP2 (Ki = 5.4 nM), and inhibits growth of MDA-MB-231 breast cancer (IC50 = 11.0 nM) and SK-OV-3 ovarian cancer (IC50 = 28.2 nM) cell lines. With an improved pharmacokinetic profile compared to previous bivalent Smac mimetics, SM-1200 effectively induces rapid and durable tumor regression in the MDA-MB-231 xenograft model. These findings suggest SM-1200 is a promising Smac mimetic and warrants extensive evaluation as a potential candidate for clinical development. Pharmacokinetic (PK) studies of bivalent Smac mimetics were performed in male Sprague Dawley rats (body weight: 250–270 g) by Medicilon. Before the pharmacokinetic studies, animals were carotid cannulated.

Prostate cancer (PCa) is a major global health concern. The androgen receptor (AR), a key member of the nuclear hormone receptor superfamily, is vital for prostate gland development and the maintenance of male secondary sexual characteristics. ARD-2051 is a potent and orally bioavailable AR PROTAC degrader. In vitro microsomal metabolic stability studies of AR degraders were performed in Medicilon. The in vitro plasma stability of a test compound was studied in human, mouse, rat, dog and monkey plasmas in Medicilon. Plasma protein binding of a test compound was assessed by equilibrium dialysis method with dialysis membrane strips in Medicilon. The CYP inhibition of a test compound was studied in human liver microsomes in Medicilon. PK studies in mice, rats and dogs were performed in Medicilon. In mouse, ARD-2051 has an excellent overall PK profile, with a low clearance (Cl = 3.7 ml/min/kg), a moderate volume of distribution (Vss = 1.3 L/kg), a half-life of approximately 5 h with both IV and oral routes of administration, and an excellent oral exposure with a good oral bioavailability (F) of 53%. In rat, ARD-2051 has a low-moderate clearance in rats (Cl = 10.2 ml/min/kg), a moderate volume of distribution (Vss = 1.3 L/kg), a half-life of 2-2.3 h with intravenous (IV) and oral routes of administration, and achieves an excellent oral bioavailability (F) of 82%. In dog, ARD-2051 has a low-moderate clearance (Cl = 4.6 ml/min/kg), a good volume of distribution (Vss = 2.8 L/kg), a long half-life of 8.9 h with IV route of administration and 21.1 h with oral route of administration, an excellent oral exposure (Cmax = 294 ng/ml and AUC=1822 h*mg/ml at 1 mg/kg), and an oral bioavailability (F) of 46%. These data indicate that ARD-2051 has favorable pharmacokinetic properties and excellent oral bioavailability in mice, rats, and dogs.

Jellies offer a palatable alternative to traditional tablets, improving medication adherence in children and the elderly. A study comparing different formulations of common cold medicines (syrup, jellies, and tablets) revealed that while none were bioequivalent according to FDA standards, jellies and syrup exhibited similar absorption rates and extents. Tablets, however, significantly delayed and reduced drug absorption compared to the syrup. These findings suggest that jellies can be a patient-friendly formulation with comparable bioavailability to syrup. To evaluate the effect of jelly formulation on the bioavailability of cold medicines, two types of jellies were prepared for a fixed-dose combination of acetaminophen (AAP), chlorpheniramine maleate (CPM), dextromethorphan hydrobromide (DMH), and dl-methylephedrine hydrochloride (MEH). A pharmacokinetic study was performed in beagle dogs after oral administration in Medicilon Preclinical Research (Shanghai) LLC (Shanghai, China). The plasma concentration profiles of AAP, CPM, DMH, and MEH are presented in the figure below. As shown in the initial plasma concentration profile for 4 h, the jellies and syrup showed rapid absorption of AAP, while both tablets retarded the absorption of AAP exhibiting lower Cmax and delayed Tmax. The jellies had less delay in the absorption rate and better bioavailability than the tablets.

作为SAPU的战术合作同伴，918博天堂凭借一站式生物医药临床前研发服务平台，为Sapu003提供了CMC放行验证（在进行中）、药代动力学、安全性评价以及IND申报等无缝衔接、高效联动的临床前研发服务，为其IND申报按下加快键。

918博天堂作为济民可信的持久合作同伴，为JMZ-2102和JMZ-2102胶囊提供了从适应症设计、活性成分筛选到系统药效学评价的服务。?双方协同互补，为该药物的高效推动和成功获批临床提供了关键支持。

作为艾立康药业的合作同伴，918博天堂凭借扎实的药效评价能力和高质量的服务，为ALK2401片提供了临床前药效学钻研支持，有力加快了该药物的研发过程。

918博天堂作为横琴新创益的战术合作同伴，为F-02-2-Na提供了切合中美双报尺度的药效试验服务，助力其急剧获批临床。