seliciclib (CYC202) / Cyclacel, Cedars-Sinai - LARVOL DELTA

Construction of a human epidermal growth factor receptor 2-related gene risk model for predicting breast cancer prognosis. (PubMed, Oncol Lett) - "AS601245, AP.24534 and roscovitine were the top three chemotherapeutic agents showing the highest sensitivity differences between the risk groups. The RT-qPCR results indicated that the expression of electron transfer flavoprotein subunit α, rap guanine nucleotide exchange factor-like 1, keratin 7, cluster of differentiation 24, proline rich 15-like, arachidonate 15-lipoxygenase type B, ELOVL fatty acid elongase 2 and C-X-C motif chemokine ligand 9 was consistent with the results of bioinformatic analysis. In conclusion, the HER2-related risk model and nomogram developed in the present study demonstrated high accuracy in predicting patient survival."

Journal • Tumor mutational burden • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ALOX15 • ALOX15B • CXCL9 • ER • HER-2 • KRT7 • PGR • TMB

Design, synthesis and molecular docking of Pyrazolo[3,4-b]pyridine derivatives as potential CDK2 pathway inhibitors in colorectal cancer cells. (PubMed, Bioorg Chem) - "However, they displayed a dose-dependent inhibition of CDK2 kinase activity in in-vitro ADP-Glo™ assay with IC50 values of 23.47 and 82.04 nM, respectively, compared to 0.51 and 700 nM for Dinaciclib and Roscovitine, respectively. Compound 6 downregulated CDK2 protein targets involved in DNA replication process; Polα, MCM7, ORC2, and ORC4 in CRC cell lines. Subjected to cell cycle analysis, HCT-116 and HT-29 treated with compound 6 demonstrated pre-G1 phase arrest with no similar observation in S phase."

Journal • Colorectal Cancer • Oncology • Solid Tumor • MCM7

A prognostic model for breast cancer survival based on PCD and m6A gene interactions. (PubMed, Front Immunol) - "A key finding from drug sensitivity analysis was that the high-risk group exhibited significantly increased sensitivity to several drugs, including CCT018159, rapamycin, vinblastine, metformin, and roscovitine. Moreover, the expression levels of SESN3, CRIP1, DPP4 and PIK3CA were significantly upregulated in breast cancer samples compared to control samples. This study constructed a risk model based on seven prognostic genes, offering new potential strategies for breast cancer therapy."

Biomarker • Journal • Breast Cancer • Herpes Simplex • Infectious Disease • Oncology • Solid Tumor • ANXA5 • CRIP1 • DAXX • MYD88 • PIK3CA

Eco-friendly synthesis of novel pyrazole derivatives and their anticancer and CDK2 inhibitory activities. (PubMed, RSC Adv) - "Compounds 4, 7, and 10 revealed significant CDK2 inhibitory activities with comparable potencies (IC50 = 0.75, 0.77 and 0.85 µM, respectively) to that of roscovitine (IC50 = 0.99 µM)...Further investigation on the mechanism demonstrated that 5 induced apoptosis, increased the proapoptotic protein Bax level, and reduced the antiapoptotic Bcl-2 level in the cells of MCF-7. Finally, the molecular docking study showed bioactive analogues that fit well in the CDK2 active site via various interactions."

Journal • Oncology • BCL2

Multi-kinase-mediated alterations in Tau phosphorylation, synaptic proteins, and choline metabolism in a human neuronal in vitro model exposed to the elastin-derived hexapeptide VGVAPG. (PubMed, Neuropharmacology) - "Therefore, this study aimed to assess the effects of VGVAPG on Tau phosphorylation, synaptic proteins, choline metabolism, and the involvement of specific kinases in a human neuronal in vitro model, using selective inhibitors (Roscovitine, TDZD-8, SCH772984, SK1). Overall, our findings provide novel insights into the possible contribution of the elastin-derived VGVAPG hexapeptide to the pathogenesis of aging-related neurodegeneration. While our model does not definitively confirm an AD-like phenotype, these results support the need for further investigation in more physiologically relevant systems."

Journal • Preclinical • CNS Disorders • Pain • CDK5 • CIP2A • PTEN

Optimized protocols of meiotic arrest maintenance improved in vitro maturation of ovine oocytes. (PubMed, Reprod Fertil Dev) - "Findings are critical for refining MAM and IVM protocols and for advancing understanding of mechanisms governing oocyte meiotic arrest and maturation."

Journal • Preclinical

Use of microbiome analysis as a complementary endpoint in clinical trials. (PubMed, iScience) - "Specific taxa, such as Tannerella and Granulicatella elegans, showed increased abundance, while Streptococcus decreased with dose. These results suggest that R-roscovitine may influence microbial dynamics in a personalized and dose-dependent manner, supporting the inclusion of microbiome profiling as an exploratory endpoint in clinical trials."

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

A novel risk model incorporating 4 mitochondrial unfolded protein response-related genes to predict the prognosis, gene mutation landscape, and immunotherapy response in lung adenocarcinoma. (PubMed, Eur J Med Res) - "The 4 MRGs may contribute to the understanding on UPRmt in LUAD and the development of relevant medicine in clinical practice."

Biomarker • IO biomarker • Journal • Tumor mutational burden • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ANLN • CREBBP • FAM83A • KDM6B • KRT6A • LRPPRC • TMB

Development and validation of a novel signature to predict the survival and affect the immune microenvironment of esophageal squamous cell carcinoma: epigenetic-related genes. (PubMed, Front Immunol) - "Drug sensitivity analysis identified four promising therapeutic compounds-PD-0325901, Bryostatin-1, ATRA, and Roscovitine-with potential clinical utility for ESCC treatment. The findings of this study offer clinically relevant insights for prognostic stratification and characterization of the immune microenvironment in ESCC patients. Moreover, these results provide novel perspectives that may contribute to the development of more effective prognostic tools and targeted therapeutic strategies for ESCC management."

IO biomarker • Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • BMI1 • BUB1 • CD8 • CHEK1 • GSE1 • IDO1 • NCOR1 • SAP30L • SATB1 • SSRP1

Targeting Loss of the Tumor Suppressor TENT5C in Multiple Myeloma (ASH 2023) - "Inhibitors targeting the cell cycle (roscovitine, apigenin, SP60012) and angiogenesis (amsacrine) were selected for validation and further investigation. Our results indicate a tumor suppressor role of TENT5C in MM, with antiproliferative properties and a susceptibility to spliceosome and NHEJ inhibitors. The HTP screen identified other targets that are currently undergoing validation leading to the identification of the molecular mechanisms underlying this function."

Hematological Malignancies • Multiple Myeloma • Oncology • NT5C • TENT5C

Schiff Base Compound of (E)-1-(((4-chloro-2-hydroxyphenyl)imino)methyl)naphthalen-2-ol as CDK2 Inhibitory Agent: Structural Characterization, Density Functional Theory Computational, and In Silico studies. (PubMed, Chem Biodivers) - "Docking results showed that HNC achieved a binding score of -8.75 kcal/mol, slightly lower than the reference inhibitor Roscovitine (RVT), which scored -9.41 kcal/mol. MM-GBSA calculations yielded ΔGtotal values of -40.95 kcal/mol for HNC and -41.14 kcal/mol for RVT, suggesting comparable binding affinities. Generally, our findings pose HNC as a credible CDK2 inhibitor and tractable starting point for optimization toward selective antiproliferative agents."

Journal • Oncology

Steroidal Alkaloids from Sarcococca saligna (Buxaceae): In Vitro and In Silico Evaluation of Their Cytotoxic Potential. (PubMed, ACS Omega) - "Additionally, extended 200 ns molecular dynamics simulations further validated the complexes, revealing stable RMSD, reduced SASA, favorable hydrogen bonding, and strong MM-GBSA binding free energies (△G_bind = -42.6 kcal·mol-1 for sarcorine C vs -40.8 kcal·mol-1 for roscovitine). These findings establish S. saligna as a promising source of anticancer steroidal alkaloids and report, for the first time, the selective cytotoxic activity of sarcorine C and salonine C against colon cancer cells, supported by integrated experimental and computational evidence."

Journal • Preclinical • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • BCL2 • CDK2 • CYP17A1 • MMP2

Roscovitine alleviates PTSD-like cognitive impairment by inhibiting CDK5-mediated Tau hyperphosphorylation. (PubMed, Brain Res Bull) - "CDK5-mediated hy-perphosphorylation of Tau at Ser202/Thr205 (AT8) in the hippocampus represents a cru-cial pathological cascade contributing to PTSD cognitive impairments. Early intervention with Rosc shows promising therapeutic potential of PTSD by targeting CDK5."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry

Straightforward synthesis and in silico evaluation of pyrazolylthiazolidinone derivatives as prospective antiproliferative agents. (PubMed, Bioorg Chem) - "In vitro antiproliferative screening against HCT-116 (colon) and A549 (lung) cancer cell lines identified compounds 3c (2,4-dihydroxybenzylidene) and 3a (4-dimethylaminobenzylidene) as the most potent, with stronger activity than the reference drugs doxorubicin and roscovitine, and reduced toxicity toward normal fibroblast (WI-38) cell line. ADME predictions further showed favorable gastrointestinal absorption, lipophilicity, oral bioavailability, and drug-likeness for thiazolidinones 3a, 3b, and 3 f. Collectively, these findings highlight these derivatives as promising scaffolds for further development of antiproliferative therapies."

Journal • Lung Cancer • Oncology

Munc13-1 restoration mitigates presynaptic pathology in spinal muscular atrophy. (PubMed, Nat Commun) - "Here, we show that pharmacological stimulation with Roscovitine triggers the assembly of Munc13-1 release sites that relies on its local translation...Furthermore, SMA mice cross-bred with a conditional knock-in mouse expressing modified Munc13-1 with a heterologous 3'UTR display attenuated synapse and neurodegeneration and improved motor function. Identifying Munc13-1 as an SMA modifier underscores the potential of targeting synapses to mitigate neuromuscular dysfunction in SMA."

Journal • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SYP

Progesterone induction of tau phosphorylation during the differentiation of human embryonic stem cells into neuroectodermal rosettes. (PubMed, J Alzheimers Dis Rep) - "The neuroectodermal rosettes were then treated with and without LiCl (Cdk5 inhibitor) or roscovitine (GSK-3β inhibitor) and assayed for the expression of tau, P-tau, nestin (an early marker of neurogenesis), Cdk5 and GSK-3β. These preliminary results suggest that progesterone induces tau expression and its phosphorylation during the differentiation of neuroectodermal rosettes from hESC and suggest that tau and its phosphorylation is obligatory for neuronal precursor cell mitosis. The parallels between neural embryogenesis and neurodegeneration are discussed in the context of tau phosphorylation and the aberrant re-entry of neurons into the cell cycle in AD."

Journal • Alzheimer's Disease • CNS Disorders • Neuroblastoma • Oncology • Solid Tumor • CDK5 • NES

Multicenter Study of Seliciclib (R-roscovitine) for Cushing Disease (clinicaltrials.gov) - P2 | N=13 | Recruiting | Sponsor: Cedars-Sinai Medical Center | Trial completion date: Aug 2025 ➔ Aug 2026 | Trial primary completion date: Aug 2025 ➔ Aug 2026

Trial completion date • Trial primary completion date • Cushing’s Disease • SSTR

Design, synthesis, biological and computational evaluation of novel S/N-glycerolyl and peptide-conjugated [1,2,4]triazolo[1,5-a]pyrimidine derivatives as potent CDK2 inhibitors for anticancer therapy. (PubMed, Bioorg Chem) - "Mechanistic validation confirmed 14c as a superior CDK2 inhibitor (IC50 = 0.21 μM, ∼2-fold more potent than roscovitine) with excellent kinase selectivity (S10 = 0.13)...Molecular docking and extensive 100 ns MD simulations revealed a stable, high-affinity binding mode (Kd ∼175-207 nM), elucidating the structural basis for its efficacy. These findings highlight peptide conjugate 14c as a breakthrough lead compound, demonstrating significant promise for development into a novel, selective CDK2- targeted anticancer therapeutic."

Journal • Oncology

CDK2 inhibitors: rationally directed discovery of a novel potent lead derived from cyclohepta[e]thieno[2,3-b]pyridine. (PubMed, RSC Med Chem) - "Notably, the novel lead compound 8b exhibited approximately 2.5-fold greater potency than roscovitine. Molecular docking studies further supported the experimental findings and provided structural insights for future optimisation of this promising CDK2 inhibitor scaffold."

Journal • Breast Cancer • Oncology • Solid Tumor • ANXA5 • CCNE1

Downregulating Cdk5 reverses hippocampal neuron ferroptosis by regulating the AMP-activated protein kinase pathway and "M1" polarized microglia. (PubMed, J Neuropathol Exp Neurol) - "Treatment with the Cdk5 inhibitor (S)-roscovitine (Ros) and/or an AMPK pathway activator metformin (Met) were investigated in a middle cerebral artery occlusion/reperfusion (MCAO/R) model in C57BL/6J mice...In vitro assays revealed that Ros and Met inhibited the proinflammatory reactions of BV2 microglia and the damage and ferroptosis of HT22 cells after OGD/R stimulation; these effects were also reversed by CC. These results indicate that targeting Cdk5 and AMPK mitigated microglia-mediated neuroinflammation and reduced neuronal ferroptosis in ischemic stroke models."

Journal • Cardiovascular • CNS Disorders • Inflammation • Ischemic stroke • CDK5

Comparative Study of Conventional, Grinding, and Microwave-Assisted Synthesis of Aminopyrazolones and Diaminopyrazoles: Exploring the Antitumor Activity, Dual CDK-2/CA IX Inhibition Potential, and Apoptosis Induction. (PubMed, Drug Dev Res) - "Entity 4 exhibited promising dual inhibition of CDK-2 and CA IX with IC50 at the micromolar level, which exceeded that of Roscovitine by three times and nearly half that of acetazolamide. Additionally, the superior derivative 4 stimulated MCF-7 cycle arrest at S phase through apoptotic induction which is supported by the upregulation of Bax and Caspase-8 and the downregulation of Bcl-2 and Cyclin E. The in silico studies showed acceptable predicted ADME and physicochemical properties together with the strong interaction between the superior compounds and both CDK-2 and CA IX binding sites inspiring such hybrids as potential lead dual inhibitors."

Clinical • Journal • Oncology • BAX • BCL2 • CASP8

Exploring the effects of roscovitine, serum starvation, and contact inhibition at G0/G1 arrest in northern tiger cat dermal fibroblasts. (PubMed, In Vitro Cell Dev Biol Anim) - "The SS for 24 h is the most efficient method of G0/G1 arrest for northern tiger cat fibroblasts. However, adjustments are still necessary to optimize cell arrest for northern tiger cat fibroblasts."

Journal • Respiratory Syncytial Virus Infections

(R)-6-[N-(3-(4-chlorophenyl) propyl] derivative of (R)-roscovitine inhibits lung carcinoma progression via cyclin-dependent kinase suppression. (PubMed, Bioorg Med Chem) - "In silico docking studies revealed a strong and stable interaction with CDK13, with a binding affinity of -8.0 kcal/mol. Compound 4 g demonstrates promising anticancer potential, likely mediated by CDK inhibition with comparatively lower toxicity toward normal cells, however, it requires further toxicological assessment and preclinical studies."

Journal • Breast Cancer • Lung Cancer • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • CDK13

Investigating the molecular mechanisms, drug prediction, and validation of CCNA2 and MAD2L1 in esophageal squamous cell carcinoma based on bioinformatics. (PubMed, BMC Med Genomics) - "CCNA2 and MAD2L1 may be potential biomarkers for ESCC, providing a novel basis for understanding the molecular mechanisms underlying ESCC pathogenesis.Additionally, the potential drugs predicted for CCNA2 may emerge as a new hope for ESCC patients in the future."

Biomarker • Journal • Bladder Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • ATF1 • CCNA2 • CD8 • CDK1 • CEBPA • MAD2L1 • PAX3 • TOP2A

LncRNA H19-Encoded Micropeptide altH19 Promotes DNA Replication and Mitosis in Myeloma Cells by Enhancing the Phosphorylation of CDK2 at Threonine 160. (PubMed, Cell Prolif) - "Notably, altH19 was able to restore phosphorylation levels of CDK2 and RB that were otherwise suppressed by the CDK2-selective inhibitor Seliciclib. In summary, we identify altH19 as a novel lncRNA-derived micropeptide with a pivotal role in myeloma progression, highlighting the therapeutic potential of targeting the altH19-CDK2-RB axis in MM treatment."

Journal • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • E2F1