ArticleMolecular cancer2012
P276-00, a cyclin-dependent kinase inhibitor, modulates cell cycle and induces apoptosis in vitro and in vivo in mantle cell lymphoma cell lines.
Article in Molecular cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 41 citations in OpenAlex.
- A phase II, single-arm, open-label, multicenter study to evaluate the efficacy and safety of P276-00, a cyclin-dependent kinase inhibitor, in patients with relapsed or refractory mantle cell lymphoma.Clinical lymphoma, myeloma & leukemia · 2015Trial
- CDK1 Signaling in Cancer Treatment: Advances in AI-based Strategies and Tools for New Cancer Drug Discovery.Combinatorial chemistry & high throughput screening · 2026Article
- Cyclin Dependent Kinases in Antiviral Drug Discovery.Current medicinal chemistry · 2025Review
- Insights into the structural and functional activities of forgotten Kinases: PCTAIREs CDKs.Molecular cancer · 2024Review
- Cancer therapy by cyclin-dependent kinase inhibitors (CDKIs): bench to bedside.EXCLI journal · 2024Review
- Novel benzo chromene derivatives: design, synthesis, molecular docking, cell cycle arrest, and apoptosis induction in human acute myeloid leukemia HL-60 cells.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- CDK9 inhibitors in cancer research.RSC medicinal chemistry · 2022Review
- Review
- Article
- CDK inhibitors in cancer therapy, an overview of recent development.American journal of cancer research · 2021Review
- Cyclin Dependent Kinase 9 Inhibitors for Cancer Therapy.Journal of medicinal chemistry · 2016Article
- Mantle cell lymphoma in the era of precision medicine-diagnosis, biomarkers and therapeutic agents.Oncotarget · 2016Review
- Lipidoid nanoparticle mediated silencing of Mcl-1 induces apoptosis in mantle cell lymphoma.Experimental biology and medicine (Maywood, N.J.) · 2016Article
- Insights on Structural Characteristics and Ligand Binding Mechanisms of CDK2.International journal of molecular sciences · 2015Review
- Targeting cell cycle regulators in hematologic malignancies.Frontiers in cell and developmental biology · 2015Review
- Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs.Cell death and differentiation · 2014Article
- Cyclin-dependent kinase inhibitor therapy for hematologic malignancies.Expert opinion on investigational drugs · 2013Review
- Anticancer Alkaloids from Trees: Development into Drugs.Pharmacognosy reviewsReview
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMantle cell lymphoma (MCL) is a well-defined aggressive lymphoid neoplasm characterized by proliferation of mature B-lymphocytes that have a remarkable tendency to disseminate. This tumor is considered as one of the most aggressive lymphoid neoplasms with poor responses to conventional chemotherapy and relatively short survival. Since cyclin D1 and cell cycle control appears as a natural target, small-molecule inhibitors of cyclin-dependent kinases (Cdks) and cyclins may play important role in the therapy of this disorder. We explored P276-00, a novel selective potent Cdk4-D1, Cdk1-B and Cdk9-T1 inhibitor discovered by us against MCL and elucidated its potential mechanism of action.
methodsThe cytotoxic effect of P276-00 in three human MCL cell lines was evaluated in vitro. The effect of P276-00 on the regulation of cell cycle, apoptosis and transcription was assessed, which are implied in the pathogenesis of MCL. Flow cytometry, western blot, immunoflourescence and siRNA studies were performed. The in vivo efficacy and effect on survival of P276-00 was evaluated in a Jeko-1 xenograft model developed in SCID mice. PK/PD analysis of tumors were performed using LC-MS and western blot analysis.
resultsP276-00 showed a potent cytotoxic effect against MCL cell lines. Mechanistic studies confirmed down regulation of cell cycle regulatory proteins with apoptosis. P276-00 causes time and dose dependent increase in the sub G1 population as early as from 24 h. Reverse transcription PCR studies provide evidence that P276-00 treatment down regulated transcription of antiapoptotic protein Mcl-1 which is a potential pathogenic protein for MCL. Most importantly, in vivo studies have revealed significant efficacy as a single agent with increased survival period compared to vehicle treated. Further, preliminary combination studies of P276-00 with doxorubicin and bortezomib showed in vitro synergism.
conclusionOur studies thus provide evidence and rational that P276-00 alone or in combination is a potential therapeutic molecule to improve patients' outcome in mantle cell lymphoma.
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