Feitelson MA, Arzumanyan A, Kulathinal RJ et al (2015) Sustained proliferation in cancer: mechanisms and novel therapeutic targets. Semin Cancer Biol Dec 35(SupplSuppl):S25–s54. https://doi.org/10.1016/j.semcancer.2015.02.006

Article  CAS  Google Scholar 

Almalki SG (2023) The pathophysiology of the cell cycle in cancer and treatment strategies using various cell cycle checkpoint inhibitors. Pathology - Research and Practice 251:154854. https://doi.org/10.1016/j.prp.2023.154854

Hanahan D (2022) Hallmarks of cancer: new dimensions. Cancer Discov Jan 12(1):31–46. https://doi.org/10.1158/2159-8290.Cd-21-1059

Article  CAS  Google Scholar 

Matthews HK, Bertoli C, de Bruin RAM (2022) Cell cycle control in cancer. Nature Reviews Molecular Cell Biology 23(1):74–88. https://doi.org/10.1038/s41580-021-00404-3

Ding L, Cao J, Lin W et al (2020) The roles of Cyclin-Dependent kinases in Cell-Cycle progression and therapeutic strategies in human breast Cancer. Int J Mol Sci 13(6). https://doi.org/10.3390/ijms21061960

Pellarin I, Dall’Acqua A, Favero A et al (2025) Cyclin-dependent protein kinases and cell cycle regulation in biology and disease. Signal Transduction and Targeted Therapy 10(1):11. https://doi.org/10.1038/s41392-024-02080-z

Sobhani N, D’Angelo A, Pittacolo M et al (2019) Updates on the CDK4/6 inhibitory strategy and combinations in breast Cancer. Cells 6(4). https://doi.org/10.3390/cells8040321

Wang X, Zhao S, Xin Q, Zhang Y, Wang K, Li M Recent progress of CDK4/6 inhibitors’ current practice in breast cancer. Cancer Gene Ther 31(9):1283–1291. https://doi.org/10.1038/s41417-024-00747-x

Ding H, Xu W, Dai M et al (2024) Hematological toxicity of cyclin-dependent kinase 4/6 inhibitors in patients with breast cancer: a network meta-analysis and pharmacovigilance study. Expert Opin Drug Saf 1–9. https://doi.org/10.1080/14740338.2024.2348566

Shen J, Luo P, Xu J (2024) Adverse event profiles of CDK4/6 inhibitors: data mining and disproportionality analysis of the FDA adverse event reporting system. Ther Adv Drug Saf 15:20420986241278498. https://doi.org/10.1177/20420986241278498

Article  PubMed  PubMed Central  Google Scholar 

Lin W, Zeng Y, Weng L, Yang J, Zhuang W (2024) Comparative analysis of adverse events associated with CDK4/6 inhibitors based on FDA’s adverse event reporting system: a case control pharmacovigilance study. BMC Pharmacol Toxicol 9(1):47. https://doi.org/10.1186/s40360-024-00770-6

Article  CAS  Google Scholar 

Ge R, Wang BY, Jiang ZF (2022) [Expert consensus on the management of adverse events of CDK4/6 inhibitors in breast cancer]. Zhonghua Zhong Liu Za Zhi Dec 23(12):1296–1304. https://doi.org/10.3760/cma.j.cn112152-20220825-00578

Article  Google Scholar 

Sledge GW Jr., Toi M, Neven P et al (2017) MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast Cancer who had progressed while receiving endocrine therapy. J Clin Oncol 1(25):2875–2884. https://doi.org/10.1200/jco.2017.73.7585

Article  CAS  Google Scholar 

Goetz MP, Toi M, Campone M et al (2017) MONARCH 3: abemaciclib as initial therapy for advanced breast Cancer. J Clin Oncol 10(32):3638–3646. https://doi.org/10.1200/jco.2017.75.6155

Article  CAS  Google Scholar 

Zhang J, Wang X, Wang X et al (2021) Phase 1a study of the CDK4/6 inhibitor, FCN-437c, in Chinese patients with HR + /HER2- advanced breast cancer. Invest New Drugs 39(6):1549–1558. https://doi.org/10.1007/s10637-021-01133-2

Article  CAS  Google Scholar 

Zhao L, Sun Y, Yang X et al (2024) No QTc prolongation with CDK 4/6 inhibitor FCN-437c: results of a concentration-QTc analysis from a dedicated study in adult healthy subjects. Front Pharmacol 15:1433663. https://doi.org/10.3389/fphar.2024.1433663

Article  CAS  PubMed  PubMed Central  Google Scholar 

Penner N, Xu L, Prakash C, Radiolabeled Absorption (2012) Distribution, Metabolism, and Excretion Studies in Drug Development: Why, When, and How?. Chemical Research in Toxicology 25(3):513–531. https://doi.org/10.1021/tx300050f

Robison TW, Jacobs A (2009) Metabolites in safety testing. Bioanalysis 1(7):1193–1200. https://doi.org/10.4155/bio.09.98

Article  CAS  Google Scholar 

Ge X, Ma S, Yan S et al (2023) Mass balance study of [(14)C]SHR0302, a selective and potent JAK1 inhibitor in humans. Xenobiotica 53(2):69–83. https://doi.org/10.1080/00498254.2023.2176267

Article  CAS  Google Scholar 

Pusalkar S, Zhou X, Li Y et al (2020) Biotransformation pathways and metabolite profiles of oral [(14)C]Alisertib (MLN8237), an investigational Aurora A kinase inhibitor, in patients with advanced solid tumors. Drug Metab Dispos 48(3):217–229. https://doi.org/10.1124/dmd.119.087338

Article  CAS  Google Scholar 

Lappin G (2015) A historical perspective on radioisotopic tracers in metabolism and biochemistry. Bioanalysis 7(5):531–540. https://doi.org/10.4155/bio.14.286

Article  CAS  PubMed  Google Scholar 

Yamada M, Mendell J, Takakusa H, Shimizu T, Ando O (2019) Pharmacokinetics, metabolism, and excretion of [(14)C]Esaxerenone, a novel mineralocorticoid receptor blocker in humans. Drug Metab Dispos 47(3):340–349. https://doi.org/10.1124/dmd.118.084897

Article  CAS  Google Scholar 

Meng J, Liu XY, Ma S et al (2019) Metabolism and disposition of Pyrotinib in healthy male volunteers: covalent binding with human plasma protein. Acta Pharmacol Sin 40(7):980–988. https://doi.org/10.1038/s41401-018-0176-6

Article  CAS  Google Scholar 

Murai T, Takakusa H, Nakai D et al (2014) Metabolism and disposition of [(14)C]tivantinib after oral administration to humans, dogs and rats. Xenobiotica 44(11):996–1008. https://doi.org/10.3109/00498254.2014.926572

Article  CAS  Google Scholar 

Huang M, Wu W, Qian J, Wan DJ, Wei XL, Zhu JH (2005) Body distribution and in situ evading of phagocytic uptake by macrophages of long-circulating Poly (ethylene glycol) cyanoacrylate-co-n-hexadecyl cyanoacrylate nanoparticles. Acta Pharmacol Sin 26(12):1512–1518. https://doi.org/10.1111/j.1745-7254.2005.00216.x

Article  CAS  Google Scholar 

Zheng Y, Zhang H, Liu M et al (2022) Pharmacokinetics, mass balance, and metabolism of the novel urate transporter 1 inhibitor [(14)C]HR011303 in humans: metabolism is mediated predominantly by UDP-Glucuronosyltransferase. Drug Metab Dispos 50(6):798–808. https://doi.org/10.1124/dmd.121.000581

Article  CAS  Google Scholar 

Gao H, Yang C, Hu W et al (2023) Pharmacokinetics, mass balance, tissue distribution and metabolism of [(14)C]101BHG-D01, a novel muscarinic receptor antagonist, in rats. Curr Drug Metab 24(11):770–779. https://doi.org/10.2174/0113892002275839231205111422

Article  CAS  PubMed  Google Scholar 

Zhang H, Zhang D, Ray K, Zhu M (2009) Mass defect filter technique and its applications to drug metabolite identification by high-resolution mass spectrometry. J Mass Spectrom 44(7):999–1016. https://doi.org/10.1002/jms.1610

Article  CAS  Google Scholar 

Zhang H, Ma L, He K, Zhu M (2008) An algorithm for thorough background Subtraction from high-resolution LC/MS data: application to the detection of troglitazone metabolites in rat plasma, bile, and urine. J Mass Spectrom 43(9):1191–1200. https://doi.org/10.1002/jms.1432

Article  CAS  Google Scholar 

Zheng YD, Zhang H, Zhan Y et al (2021) Pharmacokinetics, mass balance, and metabolism of [(14)C]vicagrel, a novel irreversible P2Y(12) inhibitor in humans. Acta Pharmacol Sin 42(9):1535–1546. https://doi.org/10.1038/s41401-020-00547-7

Article  CAS  Google Scholar 

Wang W, Chen C, Luo J et al (2024) Metabolism investigation of the peptide-drug conjugate LN005 in rats using UHPLCHRMS. J Pharm Biomed Anal 20:238:115860. https://doi.org/10.1016/j.jpba.2023.115860

Article  CAS  Google Scholar 

He YF, Liu Y, Yu JH et al (2023) Pharmacokinetics, mass balance, and metabolism of [(14)C]TPN171, a novel PDE5 inhibitor, in humans for the treatment of pulmonary arterial hypertension. Acta Pharmacol Sin 44(1):221–233. https://doi.org/10.1038/s41401-022-00922-6

Article  CAS  Google Scholar 

Yu J, Zhang H, Zhang Y et al (2022) Absorption, metabolism, and excretion of [(14)C]YY-20394, a highly selective PI3K-Delta inhibitor in humans. Xenobiotica 52(3):254–264. https://doi.org/10.1080/00498254.2022.2062581

Article  CAS  Google Scholar 

Cheng H, Yu J, Yang C et al (2022) Absorption, distribution, metabolism, and excretion of [(14)C]TPN729 after oral administration to rats. Xenobiotica 52(1):79–90. https://doi.org/10.1080/00498254.2022.2030504

Article  CAS  Google Scholar 

Bian Y, Zhang H, Ma S et al (2021) Mass balance, pharmacokinetics and pharmacodynamics of intravenous HSK3486, a novel anaesthetic, administered to healthy subjects. Br J Clin Pharmacol 87(1):93–105. https://doi.org/10.1111/bcp.14363

Article  CAS  Google Scholar 

Hop CE, Wang Z, Chen Q, Kwei G (1998) Plasma-pooling methods to increase throughput for in vivo Pharmacokinetic screening. J Pharm Sci 87(7):901–903. https://doi.org/10.1021/js970486q

Article  CAS  Google Scholar 

Groenland SL, Martínez-Chávez A, van Dongen MGJ et al (2020) Clinical pharmacokinetics and pharmacodynamics of the Cyclin-Dependent kinase 4 and 6 inhibitors Palbociclib, ribociclib, and abemaciclib. Clin Pharmacokinet 59(12):1501–1520. https://doi.org/10.1007/s40262-020-00930-x

Article  CAS