更新于：2024-11-01

HMG-CoA reductase x CD44

更新于：2024-11-01

基本信息

关联

项与 HMG-CoA reductase x CD44 相关的药物

YN-001

靶点

CD44 x HMG-CoA reductase

作用机制

CD44抑制剂 [+1]

在研机构

北京茵诺医药科技有限公司

原研机构

北京茵诺医药科技有限公司

在研适应症

动脉粥样硬化 [+2]

非在研适应症-

最高研发阶段临床1/2期

首次获批国家/地区-

首次获批日期1800-01-20

项与 HMG-CoA reductase x CD44 相关的临床试验

CTR20232962 / Recruiting临床1期

一项评价YN001在中国健康受试者中单次和多次给药及冠状动脉粥样硬化患者中多次给药的安全性、耐受性、药代动力学和初步疗效特征的剂量递增I期临床试验

Ia期主要目的：在中国健康受试者中，评估YN001单次和多次静脉给药剂量递增的安全性和耐受性及药代动力学特征。次要目的：在中国健康受试者中，评估YN001单次静脉给药剂量递增对QT/QTc间期的影响及多次静脉给药剂量递增的免疫原性。 Ib期主要目的：在冠状动脉粥样硬化患者中，评估YN001多次静脉给药剂量递增的安全性和耐受性；次要目的：在冠状动脉粥样硬化患者中，评估YN001多次静脉给药剂量递增的药代动力学特征、初步疗效、免疫原性和细胞因子变化。

开始日期2023-10-08

申办/合作机构

北京茵诺医药科技有限公司

NCT06048588 / Recruiting临床1/2期

A Phase I/IIa Trial to Evaluate the Safety, Tolerability, PK, and Preliminary Efficacy of Single and Multiple Ascending Doses of YN001 in Healthy Subjects and Multiple Ascending Doses of YN001 in Patient With Coronary Atherosclerosis

This study consists of two parts. The SAD and MAD of part I are a randomized, double-blind, placebo-controlled, single and multiple ascending dose study in healthy adult subjects. The MAD expansion cohort of part I is single arm and multipal ascending dose in heallthy subjects. Part II (phase Ib/IIa) is a multicenter, randomized, controlled, open label, multiple ascending dose study in patients with coronary atherosclerosis.

开始日期2023-10-08

申办/合作机构

北京茵诺医药科技有限公司

NCT05635084 / Recruiting临床1期

A First-in-human, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Intravenously Administered YN001 in Healthy Subjects

This will be a single center, randomized, double-blind, placebo-controlled, single ascending dose and multiple ascending dose study in healthy adult subjects.

开始日期2022-12-16

申办/合作机构

北京茵诺医药科技有限公司

100 项与 HMG-CoA reductase x CD44 相关的临床结果

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100 项与 HMG-CoA reductase x CD44 相关的转化医学

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0 项与 HMG-CoA reductase x CD44 相关的专利（医药）

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项与 HMG-CoA reductase x CD44 相关的文献（医药）

2022-09-01·The Korean Journal of Physiology & Pharmacology

Atorvastatin inhibits the proliferation of MKN45-derived gastric cancer stem cells in a mevalonate pathway-independent manner

Article

作者: Jung, Hye Jin ; Cho, Hee Jeong ; Choi, Ye Seul

Gastric cancer stem cells (GCSCs) are a major cause of radioresistance and chemoresistance in gastric cancer (GC). Therefore, targeting GCSCs is regarded as a powerful strategy for the effective treatment of GC. Atorvastatin is a widely prescribed cholesterol-lowering drug that inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a rate-limiting enzyme in the mevalonate pathway. The anticancer activity of atorvastatin, a repurposed drug, is being investigated; however, its therapeutic effect and molecular mechanism of action against GCSCs remain unknown. In this study, we evaluated the anticancer effects of atorvastatin on MKN45-derived GCSCs. Atorvastatin significantly inhibited the proliferative and tumorsphere-forming abilities of MKN45 GCSCs in a mevalonate pathway-independent manner. Atorvastatin induced cell cycle arrest at the G0/G1 phase and promoted apoptosis by activating the caspase cascade. Furthermore, atorvastatin exerted an antiproliferative effect against MKN45 GCSCs by inhibiting the expression of cancer stemness markers, such as CD133, CD44, integrin α6, aldehyde dehydrogenase 1A1, Oct4, Sox2, and Nanog, through the downregulation of β-catenin, signal transducer and activator of transcription 3, and protein kinase B activities. Additionally, the combined treatment of atorvastatin and sorafenib, a multi-kinase targeted anticancer drug, synergistically suppressed not only the proliferation and tumorsphere formation of MKN45 GCSCs but also the in vivo tumor growth in a chick chorioallantoic membrane model implanted with MKN45 GCSCs. These findings suggest that atorvastatin can therapeutically eliminate GCSCs.

2022-01-01·Journal of Oleo Science

Anti-HMG-CoA Reductase, Anti-diabetic, Anti-urease, Anti-tyrosinase and Anti-leukemia Cancer Potentials of Panicolin as a Natural Compound:<i>In vitro</i> and <i>in silico</i> Study

Article

作者: Song, Xiyue ; Li, Ling ; Yu, Zebing ; Ouyang, Meng ; Bani-Fwaz, Mutasem Z ; El-Kott, Attalla F

Flavonoid compounds are a group of polyphenolic molecules that are in vegetables, fruit, and grain. Laboratory studies and epidemiological investigations have indicated diverse beneficial biochemical properties of flavonoids, including anticancer, anti-inflammation, anti-oxidation, and anti-osteoporosis. We have recorded results for the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) Reductase and urease enzymes at the µM level. In this search, inhibition results of Panicolin on HMG-CoA reductase and tyrosinase enzymes recorded lower values of 113.98±14.38 and 2.57±0.20 µg /mL, respectively. Additionally, inhibition results of Panicolin on urease and α-amylase showed good values of 64.20±7.43 and 15.92±2.81 µg/mL, respectively. The chemical activities of panicolin against α-amylase, urease, tyrosinase, and HMG-CoA reductase, were determined by performing the molecular modeling study. The anti-cancer activities of panicolin were investigated against HL-60, THP-1, K562, and Molt-4 cell lines and IC50 values of Panicolin on these cell lines were obtained 12.94±1.04, 63.17±5.81, 15.05±1.02, and 10.84±0.65 µg/mL, respectively. The chemical activities of this compound against some of the expressed surface receptor proteins (Platelet-activating factor receptor, CD13, transferrin receptor, and CD44) in the cell lines were evaluated using molecular modeling calculations. The results revealed the possible interactions and their features at an atomic level. The docking scores suggested that panicolin has a significant binding affinity to the enzymes and proteins. Moreover, this compound constructed strong contacts with the enzymes and receptors. Therefore, panicolin could be a potential inhibitor for enzymes and cancer cells.

2021-12-01·BMC Cancer2区 · 医学

A novel ferroptosis-related 12-gene signature predicts clinical prognosis and reveals immune relevancy in clear cell renal cell carcinoma

2区 · 医学

ArticleOA

作者: Hong, Yingkai ; Huang, Zhuangkai ; Ou, Dehua ; Lin, Mingen ; Shen, Peilin

AbstractBackgroundClear cell renal cell carcinoma (ccRCC) is still highly aggressive and lethal even with various therapeutic approaches. As the kidney is an iron metabolism-related organ, exploring and assessing the clinical value of ferroptosis, an iron-dependent regulated cell death, is practical and important.MethodsPrognostic ferroptosis-related differentially expressed genes (DEGs) were identified from the KIRC cohort in the cancer genome atlas (TCGA) database, from which a prognostic signature was established using Lasso-penalized Cox regression analysis. Each patient in the KIRC cohort and the E-MTAB-1980 cohort (from the ArrayExpress database) was assigned a calculated signature-correlated risk score and categorized to be either in the high- or low-risk group divided by the median risk score in the KIRC cohort. Then, the independent prognostic value of the signature was further assessed by Kaplan-Meier (K-M) survival, time-dependent receiver operating characteristic (ROC) and Cox regression analyses based on overall survival (OS) in both cohorts. Finally, risk-related DEGs were identified in both cohorts and subjected to enrichment analyses for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and immune infiltration.ResultsAmong 60 ferroptosis-related genes, 32 prognostic DEGs were identified, from which we constructed a prognostic 12-gene signature with CARS1, HMGCR, CHAC1, GOT1, CD44, STEAP3, AKR1C1, CBS, DPP4, FANCD2, SLC1A5 and NCOA4. Patients in both cohorts were divided into high- and low-risk groups, which were visually distributed in two sets and had positive-risk-related mortality. The K-M survival and the ROC curves validated that the signature has prognostic value withP < 0.05 and area under the curve > 0.7 in both cohorts, respectively. Multivariate Cox regression further confirmed the risk score as an independent prognostic predictor for OS. Commonly enriched terms in GO and KEGG not only showed a high iron correlation but also, interestingly, immune relevance of 3 immune cells (macrophages, mast cells and regulatory T cells) and 1 immune-related function (antigen processing cell co-stimulation).ConclusionWe established a novel 12 ferroptosis-related-gene signature that was proven to be an independent prognostic predictor for OS and inferred to be related to tumour immunity in ccRCC; however, the underlying mechanism is still poorly characterized and needs further exploration.