CDK4/6 inhibitors: a brief overview and prospective research directions

Adon, Tenzin; Shanmugarajan, Dhivya; Kumar, Honnavalli Yogish

doi:10.1039/d1ra03820f

Cited by 35 publications

(27 citation statements)

References 69 publications

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“…Compound 66 , on the other hand, promoted apoptosis primarily through the intrinsic route, with direct inhibition of CDK6. 44 Shi et al proposed a new class of CDK4/6 inhibitors: imidazo[1′,2′:1,6]pyrido(2,3- d )pyrimidine analogs. 44,45 In the Colo-205 as well as U87MG cell lines, CDK4/6 was found to be effectively suppressed by compounds 70 and 71 .…”

Section: Molecular Targets Of Pyrido[23-d]pyrimidine Derivativesmentioning

confidence: 99%

Medicinal chemistry perspective of pyrido[2,3-d]pyrimidines as anticancer agents

et al. 2023

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Section: Molecular Targets Of Pyrido[23-d]pyrimidine Derivativesmentioning

confidence: 99%

Medicinal chemistry perspective of pyrido[2,3-d]pyrimidines as anticancer agents

et al. 2023

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“…The experimental results indicated that hUC-MSC-CM can effectively reduce the production of intracellular ROS and promote the recovery of cell motility. Cell cycle arrest can lead to a decrease in the ability of cells to proliferate [59]. UVB irradiation blocked the transition from the G1 phase to the G2 phase of the cell cycle in HaCaT cells, resulting in decreased cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics analysis of an in vitro photoaging model and protective effect of umbilical cord mesenchymal stem cell-conditioned medium

Zou

et al. 2022

Stem Cell Res Ther

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Background Skin ageing caused by long-term ultraviolet (UV) irradiation is a complex biological process that involves multiple signalling pathways. Stem cell-conditioned media is believed to have anti-ageing effects on the skin. The purpose of this study was to explore the biological effects of UVB irradiation and anti-photoaging effects of human umbilical cord mesenchymal stem cell-conditioned medium (hUC-MSC-CM) on HaCaT cells using multi-omics analysis with a novel cellular photoaging model. Methods A cellular model of photoaging was constructed by irradiating serum-starved HaCaT cells with 20 mJ/cm2 UVB. Transcriptomics and proteomics analyses were used to explore the biological effects of UVB irradiation on photoaged HaCaT cells. Changes in cell proliferation, apoptosis, and migration, the cell cycle, and expression of senescence genes and proteins were measured to assess the protective effects of hUC-MSC-CM in the cellular photoaging model. Results The results of the multi-omics analysis revealed that UVB irradiation affected various biological functions of cells, including cell proliferation and the cell cycle, and induced a senescence-associated secretory phenotype. hUC-MSC-CM treatment reduced cell apoptosis, inhibited G1 phase arrest in the cell cycle, reduced the production of reactive oxygen species, and promoted cell motility. The qRT-PCR results indicated that MYC, IL-8, FGF-1, and EREG were key genes involved in the anti-photoaging effects of hUC-MSC-CM. The western blotting results demonstrated that C-FOS, C-JUN, TGFβ, p53, FGF-1, and cyclin A2 were key proteins involved in the anti-photoaging effects of hUC-MSC-CM. Conclusion Serum-starved HaCaT cells irradiated with 20 mJ/cm2 UVB were used to generate an innovative cellular photoaging model, and hUC-MSC-CM demonstrates potential as an anti-photoaging treatment for skin.

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“…Cyclin-dependent kinase 4 (CDK4) is an oncogene that is particularly important for controlling the cell cycle and has been demonstrated in many types of cancer [ 86 , 87 ]. CDK4 and CDK6 inhibitors are used in treating patients with hormone receptor–positive breast cancers [ 88 , 89 ]. Therefore, it is clinically warranted to influence the higher level of expression controlling these proteins, i.e., the use of the hsa_circ_0014235 inhibitor.…”

Section: Exosomes As Chemoresistance Mediatorsmentioning

confidence: 99%

Small Extracellular Vesicles and Their Involvement in Cancer Resistance: An Up-to-Date Review

Słomka

Kornek

Cho

2022

Cells

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In recent years, tremendous progress has been made in understanding the roles of extracellular vesicles (EVs) in cancer. Thanks to advancements in molecular biology, it has been found that the fraction of EVs called exosomes or small EVs (sEVs) modulates the sensitivity of cancer cells to chemotherapeutic agents by delivering molecularly active non-coding RNAs (ncRNAs). An in-depth analysis shows that two main molecular mechanisms are involved in exosomal modified chemoresistance: (1) translational repression of anti-oncogenes by exosomal microRNAs (miRs) and (2) lack of translational repression of oncogenes by sponging of miRs through long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). At the cellular level, these processes increase the proliferation and survival of cancer cells and improve their ability to metastasize and resist apoptosis. In addition, studies in animal models have shown enhancing tumor size under the influence of exosomal ncRNAs. Ultimately, exosomal ncRNAs are responsible for clinically significant chemotherapy failures in patients with different types of cancer. Preliminary data have also revealed that exosomal ncRNAs can overcome chemotherapeutic agent resistance, but the results are thoroughly fragmented. This review presents how exosomes modulate the response of cancer cells to chemotherapeutic agents. Understanding how exosomes interfere with chemoresistance may become a milestone in developing new therapeutic options, but more data are still required.

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CDK4/6 inhibitors: a brief overview and prospective research directions

Abstract: The discovery of cyclin-dependent kinases (CDK) and their mechanism in regulating the cell cycle process was considered a game-changer in cancer therapy.

Cited by 35 publications

References 69 publications

Medicinal chemistry perspective of pyrido[2,3-d]pyrimidines as anticancer agents

Medicinal chemistry perspective of pyrido[2,3-d]pyrimidines as anticancer agents

Multi-omics analysis of an in vitro photoaging model and protective effect of umbilical cord mesenchymal stem cell-conditioned medium

Small Extracellular Vesicles and Their Involvement in Cancer Resistance: An Up-to-Date Review

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