Jul 11,2025

Sirt6抑制可延緩自免性腦脊髓炎發作，本研究中PK實驗通過尊龍凱時進行

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.

Jul 11,2025

端錨聚合酶抑制劑G007-LK具有治療結直腸癌的潛力，本研究中PK實驗通過尊龍凱時進行

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.

Jul 11,2025

Cetagliptin通過抑制DPP-4/增加GLP-1降低血糖，可用于治療2型糖尿病，本研究中GLP-1檢測通過尊龍凱時進行

Cetagliptin demonstrates the great potential for treatment with type 2 diabetes patients based on the inhibition of DPP-4, the increase in GLP-1 and insulin, the decrease in glucose, and might be more effective in DPP-4 inhibition than sitagliptin. This study was conducted in a small, selected population of healthy subjects with normoglycaemia. The results suggest that Cetagliptin, at doses ≥50 mg once daily (QD), exhibited minimal accumulation, inhibited plasma DPP-4 activity by >80% over a 24-hour dosing interval, and increased active glucagon-like-1 peptide (GLP-1) levels without producing hypoglycaemia. The active GLP-1 assays were performed by Medicilon Preclinical Research LLC. Generally, Cetagliptin has favourable clinical tolerability and safety.

Jul 10,2025

JX01是一種抗心力衰竭候選藥物，具有良好的PK特性和安全性。PK實驗通過尊龍凱時進行

Heart failure (HF), known as the terminal stage of various cardiovascular diseases, is characterized by poor prognosis and high mortality. JX01 a promising anti-HF drug candidate, showed good pharmacokinetic and safety profiles. JX01 exhibits better cardiomyocyte protective effects than EMPA in vitro. JX01 exhibits lower minimum effective doses than EMPA in vivo. JX01 has good pharmacokinetic properties. Pharmacokinetic studies were commissioned by Medicilon.

Jul 10,2025

TBN是一種治療缺血性卒中的新型臨床候選藥物，本研究中TBN通過尊龍凱時合成

?Stroke is one of the most devastating diseases affecting the health and life of human beings. TBN, a novel tetramethylpyrazine derivative armed with a powerful free radical-scavenging nitrone moiety, has been reported to reduce cerebral infarction in rats through multi-functional mechanisms of action. TBN may serve as a promising new clinical candidate for the treatment of ischemic stroke. Six Cynomolgus macaque monkeys were used for pharmacokinetic study. TBN were given intravenously at doses of 30 and 90?mg/kg, 3 monkeys for each dose. TBN (purity 99.3%) used in this study was synthesized by Medicilon.

Jul 10,2025

跨膜結構域寡聚體的結構測定新方法，其中TriNTA通過尊龍凱時合成

The transmembrane (TM) anchors of many signaling receptors actually play critical roles in receptor signaling, and the diversity of mechanism with which the TM regions can promote signaling is beyond the traditional views in receptor biology. Oligomer labeling (OG-label), the soluble crosslinkable protein (SCP) used is a small protein named GB1 (M.W. = 8.4 kDa). Its N-terminus is linked to a TriNTA molecule via a crosslinker to form the TriNTA-GB1 conjugate. The target TM protein to be examined has a His6-tag. The TriNTA molecule has extremely high binding affinity to His6-tag sequence (20 ± 10 nM), which can strongly attach GB1 to the individual protomers of the TMD oligomer in bicelles. TriNTA was synthesized by Medicilon.

Jul 10,2025

四價廣譜中和雙特異性抗體ISH0339的臨床前評估通過尊龍凱時進行

ISH0339, a tetravalent bispecific antibody composed of a pair of non-competing neutralizing antibodies that binds specifically to two different neutralizing epitopes of SARS-CoV-2 receptor-binding domain (RBD) and contains an engineered Fc region for prolonged antibody half-life. ISH0339 bound to SARS-CoV-2 RBD specifically with high affinity and potently blocked the binding of RBD to the host receptor hACE2. ISH0339 demonstrated greater binding, blocking and neutralizing efficiency than its parental monoclonal antibodies, and retained neutralizing ability to all tested SARS-CoV-2 variants of concern. Single dosing of ISH0339 showed potent neutralizing activity for treatment via intravenous injection and for prophylaxis via nasal spray. Preclinical studies following single dosing of ISH0339 showed favorable pharmacokinetics and well-tolerated toxicology profile. ISH0339 has demonstrated a favorable safety profile and potent anti-SARS-CoV-2 activities against all current variants of concern. Furthermore, prophylactic and therapeutic application of ISH0339 significantly reduced the viral titer in lungs. An indirect antigen ELISA assay was used for the detection of ISH0339 in rat serum (Medicilon). tbad003.pngPharmacokinetic analysis of single-dose ISH0339 administration was conducted by. Extended toxicity study of single-dose ISH0339 was conducted by Medicilon.

Jul 03,2025

特異性RET抑制劑CPT可改善阿爾茨海默病，本研究中CPT由尊龍凱時化學部門合成

Reverse electron transport (RET) at mitochondrial complex I generates reactive oxygen species (ROS) and reduces NAD+/NADH ratio. Inhibition of RET genetically or pharmacologically extends animal lifespan and ameliorates Alzheimer's disease‐related phenotypes. CPT acts as an RET inhibitor by binding to complex I (C‐I) 30 kD subunit (C‐I30 or NDUFS3) and altering its interaction with other proteins in the soluble matrix arm of C‐I involved in electron transfer. CPT was obtained from Cerepeut Inc. under a Materials Transfer Agreement between Cerepeut Inc. and Stanford University. The compound was synthesized for Cerepeut Inc. by the Chemistry Branch of Medicilon.

Jul 02,2025

口服有效的ADAMTS-4/5抑制劑異吲哚啉酰胺衍生物，可治療骨關節炎，本研究中部分化合物通過尊龍凱時合成

Osteoarthritis (OA) is the most common chronic joint disease that affects the knee or hip with symptoms including joint pain and dysfunction. OA treatment is a highly unmet medical need. Development of a disease-modifying OA drug (DMOAD) is challenging with no approved drugs on the market. Inhibition of ADATMS-4/5 is a promising OA therapeutics to target cartilage degradation and potentially can reduce joint pain and restore its normal function. Herein, researchers report the discovery and optimization of hydantoin-type ADAMTS-4/5 inhibitors featured by a novel isoindoline amide scaffold for the treatment of osteoarthritis. The most promising compound 18 showed high in vitro potency as an ADAMTS-4/5 inhibitor, good druglike properties, and oral bioavailability. Molecule 18 exhibited clear dose-dependent efficacy in two independent in vivo efficacy studies. Part of the compound synthesis was performed at Medicilon.

Jul 02,2025

口服IRAK4抑制劑可預防急性呼吸窘迫綜合征，本研究中抑制劑通過尊龍凱時合成

Acute respiratory distress syndrome (ARDS) is a critical respiratory illness associated with infection, autoimmunity, and injuries. However, to date, there are no well-proven pharmacotherapies except dexamethasone. This study is aimed to evaluate IRAK4 inhibitors as a potential treatment for ARDS-cytokine release syndrome (CRS). Researchers applied two IRAK4 inhibitors, BAY-1834845 and PF-06650833 to an inhaled lipopolysaccharide (LPS)-induced ARDS mouse model with control of high dose dexamethasone (10 mg/kg). Unexpectedly, although both compounds had excellent IC50 on IRAK4 kinase activity, only BAY-1834845 but not PF-06650833 or high dose dexamethasone could significantly prevent lung injury according to a blinded pathology scoring. Further, only BAY-1834845 and BAY-1834845 combined with dexamethasone could effectively improve the injury score of pre-existed ARDS. Compared with PF-06650833 and high dose dexamethasone, BAY-1834845 remarkably decreased inflammatory cells infiltrating lung tissue and neutrophil count in BALF. BAY-1834845, DEX, and the combination of the two agents could decrease BALF total T cells, monocyte, and macrophages. In further cell type enrichment analysis based on lung tissue RNA-seq, both BAY-1834845 and dexamethasone decreased signatures of inflammatory cells and effector lymphocytes. Interestingly, unlike the dexamethasone group, BAY-1834845 largely preserved the signatures of na?ve lymphocytes and stromal cells such as endothelial cells, chondrocytes, and smooth muscle cells. Differential gene enrichment suggested that BAY-1834845 downregulated genes more efficiently than dexamethasone, especially TNF, IL-17, interferon, and Toll-like receptor signaling. BAY-1834845 and PF-06650833 are synthesize by Medicilon.