seliciclib (CYC202) / Bio Green Med Solution, Cedars-Sinai - LARVOL DELTA

Effects of Roscovitine and Serum Starvation on the Viability and G0/G1 Synchronization in Somatic Cells from the Antillean Manatee (Trichechus manatus manatus, Linnaeus 1758). (PubMed, Zoo Biol) - "In summary, although roscovitine (12 h) and serum starvation did not compromise cell viability, neither method effectively induced G0/G1 synchronization under the conditions tested. Studies are needed to elucidate the in vitro behavior of Antillean manatee somatic cells and to optimize protocols for nuclear reprogramming applications."

Journal

Targeting CDK-2 With Novel Indole-Pyrazole Hybrids: Discovery of Potent Anticancer Agents Supported by Mechanistic and In Silico Studies. (PubMed, Drug Dev Res) - "Additionally, the consistent binding of compound 5 d within the ATP-binding pocket of CDK-2 was confirmed by molecular docking and molecular dynamics simulations, and attractive drug-like and pharmacokinetic features, similar to those of Roscovitine, were demonstrated by in silico ADMET predictions. All of these results point to compound 5 d as a promising lead scaffold for developing potent CDK-2-targeted anticancer agents."

Journal • Oncology • CDK2

The contribution of dorsal horn cyclin-dependent kinase 5 (CDK5) to the initiation and maintenance of chronic pain is defined by the nature of injury. (PubMed, Br J Pharmacol) - "MDH CDK5-p35 specifically regulates, though differently, inflammatory and neuropathic pain, making it an attractive target for the development of long-lasting analgesics in both sexes. The therapeutic indication of CDK5 inhibitors needs to consider the nature of injury."

Journal • CNS Disorders • Immunology • Neuralgia • Pain • CDK5

A patent review of cyclin-dependent kinase 5 (CDK5) inhibitors (1999-2025). (PubMed, Front Bioeng Biotechnol) - "We examine the chemical diversity, selectivity profiles, and therapeutic claims of major chemotypes, including purine analogs (e.g., roscovitine), pyrazole derivatives (e.g., dinaciclib, milciclib), indolobenzazepinones, indirubin derivatives, and emerging modalities such as peptides. Furthermore, we discuss major obstacles such as overcoming off-target toxicity against other CDKs, ensuring sufficient CNS exposure, and identifying reliable biomarkers. Lastly, we speculate on how future success will depend on new strategies such as p25-specific modulation, targeted protein degradation, and advanced delivery systems to translate CDK5' therapeutic potential into the clinic."

Journal • Review • CNS Disorders • Oncology • Targeted Protein Degradation

CDK Inhibition in Lung Cancer Alters Epithelial-Mesenchymal Transition, Autophagy, and Metabolism. (PubMed, Curr Cancer Drug Targets) - "These findings support the further development of multi-target CDK inhibitors as promising candidates to overcome tumor progression and therapeutic resistance in lung cancer."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDH1 • CDK1 • CDK2 • CDK4 • CDK6 • CDK7 • CDK9

A Macrophage/Monocyte-Related Four-Gene Signature for Prognostic Assessment of Uveal Melanoma: BTBD6, C2CD4B, CCL24, and S100A4. (PubMed, Hum Mutat) - "A significant negative correlation between RiskScore and the IC50 of XMD8-85, lapatinib, roscovitine, salubrinal, bexarotene, LFM-A13, FTI-277, and TGX221 chemotherapeutic agents was further noticed. In this study, we computationally identified genes associated with both disease progression and macrophage/monocyte-related characteristics in UVM and constructed a prognostic risk model with predicted immune infiltration patterns. These findings generate testable hypotheses that may inform future experimental studies on the immune mechanisms underlying UVM."

Biomarker • Gene Signature • Journal • Eye Cancer • Melanoma • Ocular Melanoma • Oncology • Solid Tumor • Uveal Melanoma • CD8 • S100A4

Establishment and validation of an ADP-ribosylation-related gene signature for prognostic prediction in lung adenocarcinoma. (PubMed, Discov Oncol) - "This ADP-ribosylation-based prognostic model reliably predicts LUAD survival and identifies potential biomarkers for tailored therapy."

Gene Signature • Journal • Tumor mutational burden • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ARL6IP1 • PARP1 • TMB

Identifying and validating of prognostic genes associated with myeloid cell differentiation in cervical cancer: development of a risk model based on single-cell RNA sequencing combined with bulk RNA sequencing data. (PubMed, Transl Cancer Res) - "Moreover, the half-maximum inhibitory concentration (IC50) values for 85 drugs, such as roscovitine and embelin, were markedly distinct between the two risk groups...RT-qPCR results confirmed that TNF, PTPN6, FASN, and TFRC were upregulated in CESC, consistent with the Wilcoxon test findings. This study established an MCD-associated prognostic model for CESC, highlighting its link to the TME and its potential to enhance prognostic predictions."

Journal • Cervical Cancer • Oncology • Solid Tumor • FASN

Conformational dynamics and inhibition mechanism of cyclin-dependent kinase 2: Insights from molecular docking and dynamics simulations with pyrazolopyrimidine analogues of roscovitine. (PubMed, Int J Biol Macromol) - "Alchemical binding free energy calculations corroborated the high inhibitory potency of PP1 and PP2. These findings offer molecular-level insights into structural dynamics and inhibition of CDK2 protein, contributing to the understanding of kinase regulation and supporting future macromolecule-focused drug design efforts."

Journal • Oncology

Design, synthesis, anticancer activity, and mechanistic investigation of 4,5,6,7-tetrahydrobenzo[b]thiophene carboxamides as CDK-2 inhibitors: in vitro and in silico DFT and molecular docking study. (PubMed, J Enzyme Inhib Med Chem) - "Compound 11 displayed the highest CDK-2 inhibition, exceeding roscovitine by nearly threefold. Besides, it arrested the MDA-MB-231 cell cycle at the G0/G1 phase by apoptotic stimulation. Molecular modelling showed strong binding of the bioactive analogues to the active pocket of CDK-2 receptor, suggesting their potential as lead inhibitors."

Journal • Preclinical • Oncology

Identification of Gene Signatures and Molecular Mechanisms for Diagnosing Parkinson's Disease and Nonalcoholic Fatty Liver Disease Using Machine Learning. (PubMed, Parkinsons Dis) - "Drug prediction and molecular docking identified ethinyl estradiol, mesalamine, and seliciclib as candidate therapeutics, showing strong binding affinity to the core targets. This study offers a comprehensive elucidation of the molecular ties between NAFLD and PD. The identified core genes and candidate drugs offer theoretical support for potential candidate biomarkers and therapeutic targets in comorbid NAFLD and PD."

Gene Signature • Journal • CNS Disorders • Hepatology • Inflammation • Metabolic Dysfunction-Associated Steatotic Liver Disease • Movement Disorders • Parkinson's Disease • BRD4 • CCNA2 • CEBPB • MIR128

Lead Discovery via Scaffold Refinement: Structure-Guided Optimization of 1,2,4-Triazolo[1,5-a]Pyrimidines as Potent Dual EGFR/CDK-2 Inhibitors Targeting Colorectal Carcinoma. (PubMed, Drug Dev Res) - "Leads 12c, 12i, and 22 demonstrated potent kinase inhibition, with 22 yielding a CDK-2 IC₅₀ of 0.03 µM (seliciclib: 0.02 µM), and 12c delivering an EGFR IC₅₀ of 0.12 µM (erlotinib: 0.01 µM). Promising ADMET profiles and good drug likeness are evident in these leads. These data underscore the great potential of this scaffold for developing dual EGF/CDK-2 inhibitors aimed at resistance mechanisms in more aggressive cancers and can thus be pursued further in preclinical optimization."

Journal • Colorectal Cancer • Oncology • Solid Tumor • AKT1 • BAX • BCL2 • CASP3 • EGFR

Design, synthesis, anticancer estimation, and computational studies of novel benzochromenoimidazopyrimidines as CDK-2 inhibitors and apoptosis stimulators. (PubMed, Mol Divers) - "Among the tested analogs, 6e, 6f, and 6 g exerted promising cytotoxicity toward HS 578 T cells where compound 6f exhibited significant antiproliferative activity with an IC50 of 3.06 µM, exceeding that of Lapatinib by 7.6 fold...The findings illustrated that analog 6f exerted the most potent CDK-2 inhibition with an IC50 equal to 0.277 µM, which is approximately threefold the activity of Roscovitine (0.833 µM). As well, compound 6f arrested HS 578 T cell cycle at both S and G2/M phases and stimulated apoptosis by increasing Bax and Caspase-3 expression with a concurrent decline in the expression of Bcl-2. Additionally, ADMET prediction and the binding interaction of the most active derivatives with CDK-2 have been studied in silico to evaluate their potential as important antitumor agents."

IO biomarker • Journal • Oncology • BAX • BCL2 • CASP3

Recurrent H1N1 Influenza A virus infections cause airway hyperinnervation and cough hypersensitivity via the IFN-γ-JAK-ERK1/2-CDK5 pathway. (PubMed, Am J Respir Cell Mol Biol) - "Recurrent H1N1 viral infections may cause airway hyperinnervation and cough hypersensitivity via the IFN-γ-JAK-ERK1/2-CDK5 pathways. Recurrent H1N1 viral infection-induced cough hypersensitivity may be mediated, in part, by IFN-γ-mediated airway hyperinnervation."

Journal • Chronic Cough • Cough • Immunology • Infectious Disease • Inflammation • Influenza • Pulmonary Disease • Respiratory Diseases • CDK5 • IFNG

Oxidative stress-induced mitochondrial fragmentation inhibits CREB-mediated PV regulation and facilitates caspase-3-mediated PV neuronal degeneration following status epilepticus. (PubMed, Neuropharmacology) - "In a pilocarpine-induced status epilepticus (SE) model, however, massive PV neuronal degeneration was observed accompanied by decreased CREB S133 phosphorylation and excessive mitochondrial fragmentation. N-acetylcysteine (NAC), roscovitine and Mdivi-1 attenuated SE-induced PV neuronal degeneration by preserving CREB S133 phosphorylation and mitochondrial integrity. These findings indicate that the CDK5-DRP1-CREB pathway may evoke PV downregulation under sublethal oxidative stress and lead to irreversible PV neuronal degeneration under severe pathological conditions such as SE. Therefore, our findings suggest that this signaling pathway may be a therapeutic target to preserve PV neurons in neurological and psychiatric diseases."

Journal • CNS Disorders • Epilepsy • Mental Retardation • Psychiatry • CASP3

Prognostic stratification in non-small cell lung cancer using a TIDE-informed transcriptomic signature: model development and validation. (PubMed, Transl Cancer Res) - "Exploratory drug-response modeling with pRRophetic suggested lower estimated half-maximal inhibitory concentration (IC50) values for agents including MS-275 (entinostat), PF-4708671, and roscovitine in the high-risk group. The TIDE algorithm carries prognostic information in NSCLC beyond immunotherapy settings. The proposed TIDE-informed gene signature reproduced prognostic stratification across cohorts, suggesting potential applicability to a broader NSCLC population and supporting future personalized risk stratification."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AHNAK2 • ANLN • GJB3 • PLAU • SCGB3A1 • SLC7A5 • TNFA

Isatin-triazole/imidazole hybrids as dual CDK2/VEGFR2 inhibitors with potent anti-cancer activity: design, synthesis, and biological evaluations. (PubMed, Bioorg Chem) - "These values are on par with or higher than those of the reference standards, roscovitine and sunitinib. Molecular docking and dynamics simulations helped to clarify the possible binding interactions inside the ATP-binding sites of CDK2 and VEGFR2, confirming the dual-binding mechanism that underlies their potent effects. According to all of these findings, compound 10 is a potential dual CDK2/VEGFR2 inhibitor that offers a helpful foundation for the development and optimization of future multitarget anticancer agents."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Selective effects of cyclin dependent kinase inhibitors in gammaherpesvirus reactivation from latency. (PubMed, bioRxiv) - "However, all broad spectrum CDK inhibitors tested, Dinaciclib, Alvocidib, and Seliciclib, decreased both reactivation from latency and primary lytic replication. In contrast, the impact of targeted CDK 4/6 inhibitors, Palbociclib, Ribociclib, and Abemaciclib, was more nuanced, with decreased reactivation when given concurrently, but increased reactivation when administered prior to induction. These findings were consistent for both murine gammaherpesvirus and Epstein-Barr Virus. Overall, our data indicate that CDK inhibitors may be useful for targeted treatment of gammaherpesvirus-associated cancers, but optimal use of targeted CDK 4/6 inhibitors requires careful consideration of cell state and order of therapies."

Journal • Epstein-Barr Virus Infections • Hematological Malignancies • Infectious Disease • Kaposi Sarcoma • Lymphoma • Oncology • Sarcoma • Solid Tumor

Positive net antiviral benefit of bexarotene against patient-derived archetype and rearranged BK polyomavirus isolates. (PubMed, Antiviral Res) - "They had a stronger antiviral activity than acitretin, which was more strain-specific and tazarotenic acid showing only modest effects...The CDK inhibitors Ro-3306 and roscovitine exhibited limited or no positive NAB, respectively. Notably, although the mTOR inhibitor sirolimus appeared to have additive antiviral effects when applied together with bexarotene, it displayed a negative NAB, rather attributing its activity to changes on cell growth/viability. In summary, bexarotene represents a promising therapeutic repurposing candidate for BKPyV reactivation in transplant patients, suggesting clinically achievable therapeutic efficacy. Clinical validation is warranted to translate these findings into therapeutic solutions for transplant recipients."

Journal • Nephrology • Renal Disease • Transplantation

Exploring Pyrazolo[3,4-b]Pyridine and Spiro-Oxindole Hybrids as Selective CDK2 or EGFR Inhibitors for Targeted Cancer Therapy: Design, Synthesis, and Molecular Modeling Insights. (PubMed, Drug Dev Res) - "The CDK2 inhibitory evaluation of pyrazolo[3,4-b]pyridines 6a-g and 7a-f revealed that compounds 6e, 7b, and 7c exhibited potent inhibition (IC₅₀ = 0.88, 1.89, and 1.23 μM, respectively), compared to roscovitine (IC₅₀ = 0.84 μM). Among the spiro-oxindole derivatives 8a-d, compounds 8b and 8c demonstrated remarkable EGFR inhibition (IC₅₀ = 0.13 and 0.09 μM, respectively) and significant activity against mutant EGFRT790M (IC₅₀ = 0.32 and 0.14 μM) relative to gefitinib (IC₅₀ = 0.03 and 0.18 μM, respectively)...Molecular docking studies combined with molecular dynamics simulations further supported stable ligand-protein interactions within CDK2, EGFR, and mutant EGFRT790M active sites, with favorable binding energies and conformational stability throughout 100 ns trajectories. Collectively, these findings identify compounds 6e and 8c as promising lead scaffolds for further development of CDK2 or EGFR inhibitors with potent and selective anticancer properties."

IO biomarker • Journal • Oncology • BAX • BCL2

Molecular characterisation of the trafficking rescue of defective ABCB4 variants by roscovitine analogues. (PubMed, Sci Rep) - "In addition, ensemble docking calculations suggest that the selected roscovitine analogues may directly interact with wild type or mutated ABCB4. Our results represent a new step towards the identification of pharmacological correctors for ER-retained variants of the ABCB4 transporter."

Journal • Cholestasis • Hepatology • Transplantation • ABCB4

Exploring pyrazoline-thiophene hybrids as CDK2 inhibitors: synthesis, mechanism, biological studies, and computational insights. (PubMed, RSC Med Chem) - "The potency of compound 4p (IC50 = 148 nM) against CDK2 was much higher than that of roscovitine (IC50 = 700 nM)...ADMET projections further highlighted positive drug-like qualities. Taking together, compound 4p is a promising anticancer candidate that targets CDK2 and exhibits strong in vivo efficacy, with supporting molecular evidence."

Journal • Breast Cancer • Hematological Disorders • Lung Cancer • Oncology • Solid Tumor • BCL2 • CASP9 • CDK2

Prediction of Prognosis, Tumor Microenvironment, and Drug Treatment of Colorectal Cancer Based on Retinoic Acid-Related Genes. (PubMed, J Environ Pathol Toxicol Oncol) - "Drug sensitivity prediction results revealed that AZ628, CGP-082996, CKM, Dasatinib, GNF-2, Saracatinib, Sorafenib, WH-4-023, and WZ-1-84 were more sensitive for patients in the HR group. AKT inhibitor VIII, Gemcitabine, JW-7-52-1, Mitomycin, NSC-87877, PAC-1, Pyrimethamine, QS11, and Roscovitine were more sensitive for those in the LR group. Our project identified correlations between RA-related genes and CRC. The model genes identified are essential indicators for evaluating CRC prognosis and further treating CRC."

Biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor

The CDK inhibitor Roscovitine enhances the therapeutic efficacy of anti-PD-1 in non-small cell lung cancer. (PubMed, Front Oncol) - "These findings demonstrate that Roscovitine potentiates anti-PD-1 therapy by simultaneously suppressing immunosuppressive cell populations and amplifying effector immune responses. The dual modulation of PD-L1 expression and immune cell dynamics provides a strong rationale for the clinical evaluation of Roscovitine in combination with immune checkpoint blockade in NSCLC and potentially other solid tumors."

IO biomarker • Journal • Immune Modulation • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCR2 • CD8

Novel mtDNA methylation-associated prognostic signatures in colorectal cancer. (PubMed, Front Oncol) - "Sorafenib, Salubrinal, and Roscovitine were positively correlated with the risk score, whereas WO2009093972 was negatively correlated. Additionally, this study identified several target genes such as FBXO25 with TINAG, CCDC28A with EPHB2, and SH2D6 with FCN3, with subsequent validation achieved through qPCR and western blotting. In conclusion, this study identifies three prognostic genes, providing new insights into CRC pathogenesis and potential therapeutic strategies."

Journal • Colorectal Cancer • Oncology • Solid Tumor • EPHB2