更新于：2024-12-25
Topiroxostat
托匹司他
更新于：2024-12-25
概要
基本信息
非在研机构- |
最高研发阶段批准上市 |
最高研发阶段(中国)临床3期 |
特殊审评- |
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结构
分子式C13H8N6 |
InChIKeyUBVZQGOVTLIHLH-UHFFFAOYSA-N |
CAS号577778-58-6 |
关联
55
项与 托匹司他 相关的临床试验一项评估托吡司特片治疗痛风伴高尿酸血症的多中心、随机、双盲、双模拟、阳性药平行对照的Ⅱ期临床研究
托吡司特片在中国健康受试者中进行的单中心、随机、开放、单次（空腹/餐后）口服给药、两制剂、两序列、四周期重复交叉的人体生物等效性试验
托匹司他片人体生物等效性研究（餐后）
100 项与 托匹司他 相关的临床结果
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100 项与 托匹司他 相关的转化医学
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100 项与 托匹司他 相关的专利（医药）
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412
项与 托匹司他 相关的文献（医药）2025-01-01EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Design, synthesis, and evaluation of 4-(4-methyl-4H-1,2,4-triazol-3-yl)piperidine derivatives as potential glutaminyl cyclase isoenzyme inhibitors for the treatment of cancer
Article
作者: He, Pan ; Zhou, Qingqing ; Wang, Zhuoran ; Qin, Feixia ; Xiong, Wei ; Gao, Ying ; Zhu, Fangyi ; Wu, Haiqiang ; Wu, Zhenxin ; Li, Chenyang
Upregulated glutaminyl cyclase isoenzyme (isoQC) contributes to cancer development by catalyzing pE-CD47 generation and thus enhancing CD47-SIRPα binding and subsequent "don't eat me" signals. We thus consider that isoQC could represent a novel target for cancer therapy. We previously prepared a series of diphenyl conjugated imidazole derivatives (DPCIs) and evaluated their use as glutaminyl cyclase (QC) inhibitors. Here, a new series of DPCIs was rationally designed and synthesized. As anticipated, the analogues exhibited considerably improved inhibitory potency against both QC and isoQC. Crucially, these chemicals exhibited marked selectivity toward isoQC. Further assessments established that one selected compound (27) did not affect the viability of A549, H1299, PC9, or HEK293T cells or the body weight of mice. This compound did, however, reduce pE-CD47 levels in infected A549 cells (isoQC_OE and isoQC_KD) and exhibited apparent anti-cancer effects in vivo by downregulating the level of pE-CD47 via the inhibition of isoQC activity. Taken together, these findings indicated that the compounds synthesized in this study could represent potential QC/isoQC inhibitors for the treatment of cancers.
2025-01-01JOURNAL OF INORGANIC BIOCHEMISTRY
Anticancer dinuclear Ir(III) complex activates Nrf2 and interferes with NAD(H) in cancer cells
Article
作者: Řezníčková, Eva ; Bárta, Ondřej ; Milde, David ; Štarha, Pavel ; Kryštof, Vladimír
Dinuclear complex [Ir2(μ-L1)(η5-Cp*)2Cl2](PF6)2 (1) exhibits low micromolar cytotoxic activity in vitro in various human cancer cells (GI50 = 1.7-3.0 μM) and outperformed its mononuclear analogue [Ir(η5-Cp*)Cl(L2)]PF6 (2; GI50 > 40.0 μM); Cp* = pentamethylcyclopentadienyl, L1 = 4-chloro-2,6-bis[5-(pyridin-2-yl)-1,3,4-thiadiazol-2-yl]pyridine, L2 = 5-(pyridin-2-yl)-1,3,4-thiadiazol-2-amine. Compound 1 upregulated the Keap1/Nrf2 oxidative stress-protective pathway in the treated MV4-11 acute myeloid leukemia cells. In connection with the redox-mediated mode of action of 1, its NADH-oxidizing activity was detected in solution (1H NMR), while NAD+ remained intact (with formate as a hydride source). Surprisingly, only negligible NADH oxidation was detected in the presence of the reduced glutathione and ascorbate. Following the results of in-solution experiments, NAD(H) concentration was assessed in 1-treated MV4-11 cancer cells. Besides the intracellular NADH oxidation in the presence of 1, the induced oxidative stress also led to a decrease of NAD+, resulting in depletion of both NAD+/NADH coenzymes. The discussed findings provide new insight into the biochemical effects of catalytic anticancer compounds that induce cell death via a redox-mediated mode of action.
2024-12-16CURRENT DRUG METABOLISM
Characterizing Pharmacokinetic Variability of Topiroxostat in Chinese Population: Insights from a Phase I Randomized Clinical Trial
Article
作者: Qu, Shengjun ; Fan, Hongwei ; Pang, Wenbo ; Xia, Yan ; Huang, Kaizong ; Han, LuYao ; Yu, Guo ; Zhong, Tianqi ; Chen, Yangsheng
Objective::
This Phase I clinical trial aimed to address the knowledge gap regarding topiroxostat's
use outside Japan by characterizing its pharmacokinetic profile, safety, and efficacy in healthy Chinese subjects.
Methods::
The trial followed a randomized, open-label, three-dose group design, enrolling 12 healthy participants
and administering topiroxostat at three different dose levels. The study utilized NONMEM software for
pharmacokinetic analysis, evaluating the impact of demographic and biochemical covariates on drug disposition.
Results::
Pharmacokinetic analysis shows the peak drug concentration (Cmax) under a single oral administration
of 20, 40, and 80 mg of Topiroxostat, which was found in healthy subjects to be 215.46 ± 94.04 ng/mL,
473.74 ± 319.83 ng/mL and 1009.63 ± 585.98 ng/mL, respectively. The time to peak drug concentration
(Tmax) was longer in females (0.79–0.98 h) than in males (0.53–0.93 h). Activated partial thromboplastin
time (APTT) and triglycerides (TG) were included as covariates for the typical value of the absorption rate
constant (TVKA) in our pharmacokinetic model. The dose (DOSE) was considered a covariate for the typical
value of bioavailability (TVF1), and sex (SEX) was considered a covariate for the typical value of clearance
(TVCL). The typical population values for topiroxostat included Q/F at 4.91 L/h, KA at 0.657 h-¹, Vc/F at
32.5 L, Vp/F at 30 L, and CL/F at 124 L/h.
Conclusion::
The trial successfully established the pharmacokinetic parameters of topiroxostat in a Chinese
population, confirming its safety and efficacy. The results support the need for individualized dosing strategies
and optimize therapeutic outcomes.
100 项与 托匹司他 相关的药物交易
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研发状态
批准上市
10 条最早获批的记录, 后查看更多信息
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 痛风 | 日本 | 2013-06-28 | |
| 痛风 | 日本 | 2013-06-28 | |
| 痛风 | 日本 | 2013-06-28 | |
| 高尿酸血症 | 日本 | 2013-06-28 | |
| 高尿酸血症 | 日本 | 2013-06-28 | |
| 高尿酸血症 | 日本 | 2013-06-28 |
未上市
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 糖尿病肾病 | 临床2期 | 日本 | 2014-12-30 | |
| 糖尿病肾病 | 临床2期 | 日本 | 2014-12-30 |
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临床结果
临床结果
适应症
分期
评价
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N/A | 252 | Febxostat (FBX) | 鏇築窪願鏇衊夢簾製夢(網壓膚鹹淵選蓋築夢齋) = BP129.3 ± 17.8/78.7 ± 12.4 mmHg to BP126.1 ± 16.3/76.2 ± 11.1 mmHg 鹽觸鏇衊鑰繭築鹹壓網 (獵餘遞製積膚鏇築繭艱 ) | 积极 | 2021-04-01 | ||
Topiroxostat (TPX) | |||||||
N/A | 慢性肾病 serum urate levels | urinary albumin excretion | - | 獵範製築顧壓鏇鏇網網(觸鏇蓋構艱壓構遞廠窪) = 夢夢遞築築構選醖簾願 築鹽鑰鹽艱積築簾鹽齋 (顧夢餘鑰積範鏇醖遞夢 ) | 积极 | 2015-05-21 | ||
Placebo | 獵範製築顧壓鏇鏇網網(觸鏇蓋構艱壓構遞廠窪) = 糧壓憲膚廠壓壓網醖鬱 築鹽鑰鹽艱積築簾鹽齋 (顧夢餘鑰積範鏇醖遞夢 ) |
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