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

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

New pyrazolo[1,5-a]pyrimidine derivatives as potential CDK2 inhibitors and apoptosis-driven antiproliferative agents. (PubMed, Bioorg Med Chem) - "Among the tested compounds, 7-(4-bromophenyl)-2-(methylthio)pyrazolo[1,5-a]pyrimidine-3‑carbonitrile (13 g), 7-(2,4-dichlorophenyl)-2-(methylthio)pyrazolo[1,5-a]pyrimidine-3‑carbonitrile (13j), 7-[1-(4-fluorophenyl)-5-methyl-1H-1,2,3-triazol-4-yl)-2-(methylthio)pyrazolo[1,5-a] pyrimidine-3‑carbonitrile (21c), and 7-(6-bromo-2-oxo-2H-chromen-3-yl)-2-(methylthio)pyrazolo[1,5-a] pyrimidine-3‑carbonitrile (26b) exhibited strong growth inhibition in HCT-116 cells, comparable to the reference drug roscovitine...Molecular docking studies supported these results, showing favorable interactions of compound 21c within the CDK2 active site. Overall, compound 21c emerges as a promising lead candidate for the development of selective CDK2 inhibitors exhibiting potent anti-cancer activity and low toxicity toward normal cells."

Journal • Breast Cancer • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • BCL2

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