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更新于：2025-05-16
Amdizalisib
安迪利塞
更新于：2025-05-16
概要
基本信息
原研机构 |
非在研机构- |
权益机构- |
最高研发阶段申请上市 |
首次获批日期- |
最高研发阶段(中国)申请上市 |
特殊审评突破性疗法 (中国)、特殊审批 (中国) |
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结构/序列
分子式C19H15ClN8 |
InChIKeyWKDBRCUUDXLTIM-NSHDSACASA-N |
CAS号1894229-05-0 |
关联
7
项与 安迪利塞 相关的临床试验NCT05713110
A Phase II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Tazemetostat in Combination With HMPL-689 in Patients With Relapsed/Refractory Lymphoma
CTR20212448
在中国成年男性健康受试者中研究口服30 mg/100 μCi [14C]HMPL-689混悬液后人体内物质平衡的单中心、开放、单剂量的I期临床试验
NCT04849351
A Multi-center, Single-arm, Open-label Clinical Study to Evaluate the Efficacy and Safety of HMPL-689 in Patients With Relapsed/Refractory Marginal Zone Lymphoma and Follicular Lymphoma
100 项与 安迪利塞 相关的临床结果
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100 项与 安迪利塞 相关的转化医学
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100 项与 安迪利塞 相关的专利（医药）
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2
项与 安迪利塞 相关的文献（医药）Frontiers in Pharmacology
Preclinical pharmacokinetic characterization of amdizalisib, a novel PI3Kδ inhibitor for the treatment of hematological malignancies
Article
作者: Su, Weiguo ; Xia, Sumei ; Xue, Weifang ; Li, Xiangkun ; Jiang, Shuwen ; Wang, Jian ; Sai, Yang ; Dai, Guangxiu
Amdizalisib, also named HMPL-689, a novel selective and potent PI3Kδ inhibitor, is currently under Phase II clinical development in China for treating hematological malignancies. The preclinical pharmacokinetics (PK) of amdizalisib were extensively characterized in vitro and in vivo to support the further development of amdizalisib. We characterized the plasma protein binding, blood-to-plasma partition ratio, cell permeability, hepatic microsomal metabolic stability, and drug–drug interaction potential of amdizalisib using in vitro experiments. In vivo PK assessment was undertaken in mice, rats, dogs, and monkeys following a single intravenous or oral administration of amdizalisib. The tissue distribution and excretion of amdizalisib were evaluated in rats. The PK parameters (CL and Vss) of amdizalisib in preclinical species (mice, rats, dogs, and monkeys) were utilized for the human PK projection using the allometric scaling (AS) approach. Amdizalisib was well absorbed and showed low-to-moderate clearance in mice, rats, dogs, and monkeys. It had high cell permeability without P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) substrate liability. Plasma protein binding of amdizalisib was high (approximately 90%). It was extensively distributed but with a low brain-to-plasma exposure ratio in rats. Amdizalisib was extensively metabolized in vivo, and the recovery rate of the prototype drug was low in the excreta. Amdizalisib and/or its metabolites were primarily excreted via the bile and urine in rats. Amdizalisib showed inhibition potential on P-gp but not on BCRP and was observed to inhibit CYP2C8 and CYP2C9 with IC50 values of 30.4 and 10.7 μM, respectively. It exhibited induction potential on CYP1A2, CYP2B6, CYP3A4, and CYP2C9. The preclinical data from these ADME studies demonstrate a favorable pharmacokinetic profile for amdizalisib, which is expected to support the future clinical development of amdizalisib as a promising anti-cancer agent.
Frontiers in Pharmacology
Mass balance, metabolism, and pharmacokinetics of [14C]amdizalisib, a clinical-stage novel oral selective PI3Kδ inhibitor for the treatment of non-hodgkin’s lymphoma, in healthy Chinese volunteers
Article
作者: Wang, Wei ; Sun, Chan ; Chen, Qian ; Yu, Cheng-Yin ; Liu, Gang-Yi ; Zhao, Chun-Yang ; Liu, Yan-Mei ; Wang, Jian ; Sai, Yang ; Jia, Jing-Ying ; Su, Wei-Guo ; Zhang, Li-Jun
Introduction:
Amdizalisib (HMPL-689) is an ATP-competitive PI3Kδ inhibitor currently under investigation for treating Hodgkin’s lymphoma. This study aimed to evaluate the metabolism, excretion, pharmacokinetics, and safety profile of amdizalisib in healthy human subjects to support its clinical application.
Methods:
This Phase I clinical trial included six healthy Chinese male volunteers who received a single oral dose of 30 mg/100 µCi [14C]amdizalisib suspension. Blood, urine, and fecal samples were collected to analyze pharmacokinetics, metabolic pathways, and excretion patterns.
Results:
Amdizalisib was rapidly absorbed, with a median Tmax of 2.5 h. The Cmax of 244 ± 48.9 ng/mL, and AUC0-t was 1870 ± 474 h ng/mL after a single oral dose. The blood-to-plasma total radioactivity ratio ranged from 0.561 to 0.645, indicating no significant affinity of [14C]amdizalisib and its metabolites to blood cells and the radioactive material is mainly distributed in plasma. Excretion was primarily via feces and urine, with 62.08% ± 3.00% and 37.15% ± 2.84% of the dose recovered, respectively, and over 94% of the drug excreted within 96 h. The parent drug was the main radioactive component in plasma (51.45% of total radioactivity). Additionally, 11 metabolites were identified, and the metabolic pathways include oxidation on the benzene or pyrimidine rings and conjugation with cysteine or glucuronic acid. The major metabolites in plasma were the di-oxidized and hydrogenated product (M424) and the mono-oxidized product (M406-2), accounting for 16.67% and 20.91%, respectively. Both of them are also the major radioactive components in urine and feces, among of which M424 accounted for 21.01% and 14.26%, M406-2 accounted for 8.08% and 11.30%, of the administered dose in urine and feces, respectively. In addition, the di-oxidized and methylated product (M436) was one of the major metabolites in feces accounting for 17.7% of the administered dose. Few of the parent drug was found in urine and feces, suggesting primary metabolized in the liver. No serious adverse events or drug-related deaths occured, with diarrhea as the most common adverse event.
Discussion:
These findings demonstrate that amdizalisib is rapidly absorbed, extensively metabolized, and primarily excreted via feces and urine, supporting its continued development as a potential therapeutic for Hodgkin's lymphoma.
Systematic Review Registration::
https://www.chinadrugtrials.org.cn/, identifier CTR20212448.
100 项与 安迪利塞 相关的药物交易
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研发状态
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 滤泡性淋巴瘤 | 申请上市 | 中国 | 2022-08-17 | |
| 难治性边缘区淋巴瘤 | 申请上市 | 中国 | 2022-08-17 | |
| 复发性淋巴瘤 | 临床2期 | 中国 | 2023-02-13 | |
| 难治性淋巴瘤 | 临床2期 | 中国 | 2023-02-13 | |
| 复发性边缘区淋巴瘤 | 临床2期 | 中国 | 2021-04-15 | |
| B细胞淋巴瘤 | 临床1期 | 美国 | 2019-08-26 | |
| B细胞淋巴瘤 | 临床1期 | 芬兰 | 2019-08-26 | |
| B细胞淋巴瘤 | 临床1期 | 法国 | 2019-08-26 | |
| B细胞淋巴瘤 | 临床1期 | 意大利 | 2019-08-26 | |
| B细胞淋巴瘤 | 临床1期 | 波兰 | 2019-08-26 |
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临床结果
临床结果
适应症
分期
评价
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临床1期 | 153 | 衊積膚鬱製蓋窪壓遞鹽(鏇淵膚廠範夢壓憲廠齋) = 醖鹽醖範觸鏇鏇觸窪齋 範窪網壓獵衊選網夢選 (顧構鹽憲鬱鹹觸壓構廠 ) 更多 | 积极 | 2023-06-09 | |||
临床1期 | 75 | 選鏇顧憲選餘窪糧淵齋(繭鹽鑰選壓觸淵製壓願) = 糧鏇築憲夢製鏇憲艱製 艱遞繭選簾築糧網製窪 (築觸鏇膚遞繭選製鏇構 ) 更多 | - | 2021-09-20 | |||
临床1期 | 56 | (cohort A (BID)) | 網範積壓觸餘鹽艱顧窪(蓋範獵蓋餘衊鑰壓窪製) = 30 mg QD of HMPL-689 has been selected as recommended phase 2 dose (RP2D) 鹹構鹹襯鑰構願願鬱鑰 (鬱獵齋積簾範簾選積蓋 ) 更多 | 积极 | 2020-11-05 | ||
(cohort B (QD)) |
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