J9集团

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
，J9集团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。

J9集团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
，J9集团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。

J9集团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。

J9集团作为领诺医药合作同伴
，依附一站式生物医药临床前研发服务平台
，为SLN12140项目提供了体表药效、药代、安评等研发服务
，加快了该创新药物的研发过程。

作为Eluciderm的合作同伴
，J9集团有幸为ELU42的急剧获批提供了毒理学钻研服务
，并因而荣获 Eluciderm 宣告的“卓越服务奖”。这次合作是创新药企与CRO合作创新的范例。

Experimental autoimmune encephalomyelitis (EAE) is the most common animal model of multiple sclerosis (MS), a neuroinflammatory and demyelinating disease characterized by multifocal perivascular infiltrates of immune cells. Although EAE is predominantly considered a T helper 1-driven autoimmune disease, mounting evidence suggests that activated dendritic cells (DC), which are the bridge between innate and adaptive immunity, also contribute to its pathogenesis. Sirtuin 6 (SIRT6), a NAD+-dependent deacetylase involved in genome maintenance and in metabolic homeostasis, regulates DC activation, and its pharmacological inhibition could, therefore, play a role in EAE development. The PK study was performed by Medicilon.

Colorectal tumors, in particular, often show dysregulated WNT/β-catenin signalling. G007-LK may be a candidate for use in preclinical trials to determine the efficacy of this drug in preventing growth of WNT dependent tumors. Doses of the tankyrase inhibitor G007-LK shown to be sufficient to inhibit tumor growth are well tolerated by mice within the time frames investigated. Lineage tracing from LGR5+ intestinal stem cells was reduced upon G007-LK treatment, without altering the main morphological characteristics of the intestine. Moreover, mice treated with G007-LK did not experience weight loss, suggesting that the absorptive capacity of the intestine was not negatively impacted. Medicilon Preclinical Research LCC performed the pharmacokinetic studies.