Pharmacokinetics, mass balance, and metabolism of [14C]FCN-437c, a selective and potent CDK4/6 inhibitor in humans
文献类型：期刊论文
| 作者 | Gao, Lei6; Ma, Sheng4,5; Yan, Shu6; Zhang, Hua4,5; Tian, Ling3; Li, Lize3; Diao, Lei2; Miao, Liyan1,4,5; Yang, Xiaoran3; Diao, Xingxing6 |
| 刊名 | CANCER CHEMOTHERAPY AND PHARMACOLOGY
 |
| 出版日期 | 2025-12-01 |
| 卷号 | 95期号:1页码:12 |
| 关键词 | FCN-437c CDK4/6 inhibitor Mass balance Radiopharmacokinetics Drug metabolism |
| ISSN号 | 0344-5704 |
| DOI | 10.1007/s00280-025-04779-4 |
| 通讯作者 | Miao, Liyan(miaolysuzhou@163.com) ; Yang, Xiaoran(yangxiaoran@avancpharma.com) ; Diao, Xingxing(xxdiao@simm.ac.cn) |
| 英文摘要 | This study investigated the pharmacokinetics, mass balance, and metabolism of [14C]FCN-437c, a selective and potent CDK4/6 inhibitor, in humans. Six healthy male Chinese subjects were administered a single oral dose of 200 mg [14C]FCN-437c (120 mu Ci), and plasma, urine, and feces samples were collected up to 456 h post-dose. The geometric mean Cmax of radioactivity in plasma and blood were 706 and 557 ng eq./mL, respectively, with a median Tmax of 5.0 h and a geometric mean t1/2 of 56.5 h in plasma. The primary route of elimination was fecal excretion, accounting for a mean of 77.16% of the dose, whereas urinary excretion constituted a mean of 19.19% of the administered radioactivity. UHPLC-HRMS analysis identified 12 metabolites in human plasma, urine, and feces, with 8 of them being phase I metabolites, and the major metabolic pathways were mono-oxidation and O-dealkylation. Additionally, 4 phase II metabolites were identified, including two glucuronides, one glutathione conjugate, and one cysteine conjugate. The study provides insights into the metabolic stability and clearance mechanisms of FCN-437c in human, which are essential for its further clinical development and dosing regimens. |
| WOS关键词 | BREAST-CANCER ; ABEMACICLIB ; TOXICITY ; PLASMA |
| 资助项目 | National Natural Science Foundation of China ; Liaoning Avanc Pharmaceutical Co., Ltd.[82373938] ; Liaoning Avanc Pharmaceutical Co., Ltd.[82104275] ; Liaoning Avanc Pharmaceutical Co., Ltd.[82104276] ; Liaoning Avanc Pharmaceutical Co., Ltd.[82204585] ; National Natural Science Foundation of China[2023B1111030004] ; Key Technologies R&D Program of Guangdong Province[2022YFF1202600] ; National Key R&D Program of China |
| WOS研究方向 | Oncology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001495044300001 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/317968]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Miao, Liyan; Yang, Xiaoran; Diao, Xingxing |
| 作者单位 | 1.Soochow Univ, Coll Pharmaceut Sci, Suzhou, Peoples R China 2.Shanghai Fosun Pharmaceut Grp Co Ltd, Shanghai 200233, Peoples R China 3.Liaoning Avanc Pharmaceut Co Ltd, Liaoning 121013, Peoples R China 4.Soochow Univ, Inst Interdisciplinary Drug Res & Translat Sci, Suzhou, Peoples R China 5.Soochow Univ, Affiliated Hosp 1, Suzhou 215006, Jiangsu, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201210, Peoples R China |
| 推荐引用方式 GB/T 7714 | Gao, Lei,Ma, Sheng,Yan, Shu,et al. Pharmacokinetics, mass balance, and metabolism of [14C]FCN-437c, a selective and potent CDK4/6 inhibitor in humans[J]. CANCER CHEMOTHERAPY AND PHARMACOLOGY,2025,95(1):12. |
| APA | Gao, Lei.,Ma, Sheng.,Yan, Shu.,Zhang, Hua.,Tian, Ling.,...&Diao, Xingxing.(2025).Pharmacokinetics, mass balance, and metabolism of [14C]FCN-437c, a selective and potent CDK4/6 inhibitor in humans.CANCER CHEMOTHERAPY AND PHARMACOLOGY,95(1),12. |
| MLA | Gao, Lei,et al."Pharmacokinetics, mass balance, and metabolism of [14C]FCN-437c, a selective and potent CDK4/6 inhibitor in humans".CANCER CHEMOTHERAPY AND PHARMACOLOGY 95.1(2025):12. |
入库方式： OAI收割
来源：上海药物研究所
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