dinaciclib (MK-7965) / Ligand, Merck (MSD) - LARVOL DELTA

Olutasidenib in post-venetoclax patients with mIDH1 AML. (ASCO 2023) - P1/2 | "VEN was used with azacytidine (AZA) in 8 patients, after AZA (1), and with decitabine (5), cytarabine +/- idarubicin (5), and dinaciclib (2). Olutasidenib induced durable remissions in patients with mIDH1 R/R AML, including those failing prior treatment with a venetoclax-based regimen. Clinical trial information: NCT02719574."

Clinical • Acute Myelogenous Leukemia • Hematological Disorders • IDH1

Pan-CDK and PLK1 inhibitors as a novel approach for targeted treatment of adrenocortical carcinomas. (PubMed, Eur J Endocrinol) - "This study investigated the anti-tumour efficacy of the pan-CDK inhibitors (CDKi) dinaciclib, AT7519, and SNS-032; the CDK1-cyclin B1 inhibitor cucurbitacin E (curE); the PLK1 inhibitors (PLK1i) poloxin and plogosertib; and selected combination strategies in four genetically heterogeneous ACC cell lines (NCI-H295R, JIL-2266, MUC-1, TVBF-7) and primary cultures. These results identify dinaciclib and plogosertib as the most effective inhibitors across all ACC models tested. Their simultaneous action on multiple checkpoints, alongside with their synergistic effect in selected cell lines, suggest a potential benefit of their use in ACC that needs to be further investigated in vivo."

Journal • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CCNB1 • CCNE1 • CDK1 • CDKN1A • CYP17A1 • CYP1A2 • CYP21A2 • MUC1

Veliparib and Dinaciclib in Treating Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=121 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Aug 2026 ➔ Aug 2027

Trial completion date • Oncology • Solid Tumor • BRCA • BRCA1 • BRCA2

Elimusertib exhibits strong synergy with olaparib in ovarian cancer organoids through replication fork interference. (PubMed, Sci Rep) - "Screening identified elimusertib (ATR inhibitor), proteasome inhibitors (ixazomib, carfilzomib), and dinaciclib (Cdk1/2/5/9 inhibitor) as synergistic agents with olaparib. These results demonstrate that elimusertib is a very potent ATR inhibitor for combination with olaparib and provide mechanistic insight into this synergy through replication fork interference. Because this synergy spanned both HRD and HRP organoids, these findings support further preclinical optimization and well-designed clinical evaluation of the olaparib-elimusertib combination in HGSC, with attention to dose-finding, hematologic safety, and patient selection."

Journal • Hematological Disorders • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA1 • CDK1 • HRD

Multi-omics profiling identifies CDK1 as a key mediator of mitosis through the PTN pathway in bladder cancer. (PubMed, Future Sci OA) - "Predominantly expressed in BC epithelial cells, CDK1 may be activated by PTN signaling to drive mitosis. MD simulations support Dinaciclib as a promising CDK1-targeting inhibitor."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CDK1 • PTN

Landscape of genetic ancestry-associated active drugs unique to or shared by White and Hispanic children with group 3 medulloblastomas (ISPNO 2026) - "Compounds selectively active in Hispanic-derived models but not in White-derived models reached 27 clustered predominantly around targets and pathways related to CDK-mediated cell cycle regulation (Dinaciclib), Na⁺/K⁺ ATPase–associated calcium signaling, and mTOR-linked reactive oxygen species and apoptosis signaling. In contrast, compounds preferentially active in White-derived models reached 56 were enriched for targets involved in topoisomerase-mediated DNA damage responses (Irinotecan) and microtubule-and HSP-associated cytoskeletal signaling pathways. These differences were observed at the level of pathway and target enrichment rather than individual drug effects, suggesting systematic differences in therapeutic vulnerabilities between ancestry-associated tumor groups. Together, our study uncovers reproducible genetic ancestry-based drug response profile between white and Hispanic G3 MBs, provides a biologic rational for mechanistic investigation of cancer..."

Clinical • Brain Cancer • Medulloblastoma • Solid Tumor

MECHANISMS OF RESISTANCE TO BTK INHIBITORS INDEPENDENT OF BTK AND PLCG2 MUTATIONS (EHA 2026) - "Results Seven lines of REC-1 cells that acquired resistance to pirtobrutinib or nemtabrutinib lacked BTK, PLCG2 or other known resistance- associated mutations when analyzed by tNGS (Qi J. et al...Treatment with BTKis ibrutinib or nemtabrutinib, or BTK degrader (BTKd) NX-5948 resulted in suppression of BTK phosphorylation or caused BTK degradation, respectively...Hence, BTKi resistant REC-1 did not show signiIcantly increased sensitivity to OXPHOS pathway inhibitor IACS-10759 either as single drug or in combination with BTKi/BTKd...In addition, the CDK inhibitor dinaciclib demonstrated efIcacy as monotherapy in resistant cells, and its combination with the BTKd NX-5948 showed signiIcant synergistic activity in both wild-type and resistant cells...Summary/Conclusion Dysregulation of the cell cycle contributed to acquired BTKi and BTKd resistance in REC-1 cells in the absence of BTK or PLCG2 mutation. Synergistic effects of CDK inhibitors with BTKd need to be further..."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • ANXA5 • CASP3 • CASP7 • CCNA2 • CDK1 • PLCG2

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

A brain-enriched Extracellular Vesicles liquid biopsy links bipolar disorder biology to drug candidates through Connectivity Map Analysis (CINP 2026) - "CMap nominated potential therapeutics including dinaciclib (CDK inhibitor), TGX-221 (PI3Kβ inhibitor), fatostatin (SREBP inhibitor), KW-2449 (FLT3/Aurora kinase inhibitor), acalabrutinib (BTK inhibitor), and the muscarinic M3 antagonists otilonium and diphemanil; all nominated hits met FDR-adjusted p < 0.05. Plasma NCAM1-positive EV transcriptomes capture brain-enriched signals and provide a scalable, minimally invasive readout for biomarker discovery and biological stratification in mood disorders. Crucially, integrating this liquid-biopsy signature with CMap establishes an end-to-end, mechanism-aware route from blood to actionable drug hypotheses—prioritizing compounds predicted to counteract immune-inflammatory, proliferative, and metabolic programs activated in BD. These candidates warrant independent validation in larger cohorts and experimental models and may enable a pragmatic path toward precision repurposing and longitudinal monitoring of treatment-related..."

Biopsy • Liquid biopsy • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • FLT3 • NCAM1 • PIK3CB

Identification of novel therapeutic agents using patient-derived organoids in HCC (EASL 2026) - "Among them, dinaciclib, homoharringtonine, volasertib, mocetinostat, and daunorubicin, have bene already reported as effective on HCC...Among standard treatments, only sorafenib inhibited HCC-PDOs...In keeping with this, osimertinib, another drug highlighted by the screening on HCC-PDO and currently used for EGFR-mutant lung cancer, has been reported as effective also in HCC (J... The identification of dinaciclib and homoharringtonine as potent agents aligns with recent literature on novel HCC drugs, and validates the robustness of our approach and the potential of our results. Moreover, our results disclosed a significant potential for some drug repurposing. A recent study showed that cerinitib, a drug targeting ALK mutation in advanced non-small cell lung cancer, inhibits β-catenin mutated HCC via non-canonical WNT pathway independent of ALK (J Hep Reports, 2025)."

Clinical • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • ALK • CTNNB1 • EGFR

Integrin-binding sialoprotein as an extracellular matrix-associated independent prognostic biomarker in glioma. (PubMed, BMC Cancer) - "IBSP represents an independent prognostic biomarker associated with adverse outcomes in glioma. These findings provide insight into the molecular mechanisms underlying IBSP-associated glioma progression and highlight potential therapeutic targets that may contribute to improved clinical outcomes in patients with glioma."

Biomarker • Journal • Brain Cancer • Genito-urinary Cancer • Glioma • Oncology • Prostate Cancer • Solid Tumor • CASP4 • KYNU • SIGLEC9 • SLC16A3

S0826: Dinaciclib in Treating Patients With Stage IV Melanoma (clinicaltrials.gov) - P2 | N=72 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

Discovery and validation of effective combination therapies targeting cell state-specific master regulator vulnerabilities by network-based protein activity inference in diffuse midline glioma (AACR 2024) - "Candidate drugs predicted by OncoTarget (inhibitors of individual MRs) and OncoTreat were distinct across the cell states, and we selected five drugs targeting the OPC/cycling-like cells (Trametinib, Dinaciclib, Avapritinib, Mocetinostat, and Etoposide), and four drugs targeting the AC-like cells (Ruxolitinib, Venetoclax, Napabucasin, Larotrectonib) for further validation as these states comprised most tumor cells across patients.We generated single-cell RNAseq for 95,687 cells after 5 days of treatment with either vehicle control (n = 4) or candidate drug (n = 2-3/drug) in subcutaneous SU-DIPG-17 mouse models. Notably, the combination of drugs targeting OPC/cycling-like and AC-like cells (i.e. Trametinib+Ruxolitinib and Avapritinib+Venetoclax) showed significantly lower tumor volumes after 2 weeks of treatment as compared to vehicles or each drug alone, and significant survival differences for some combinations. This work provides a precision medicine platform to..."

Combination therapy • Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor

The ubiquitin E3 ligase SCFSkk2/Cks1complex: A critical node coupling cell cycle control, tumorigenesis, and lineage fidelity in small cell lung cancer (SCLC) (AACR 2026) - "Cell lines derived from the RPPt lung tumors grew more rapidly and were more sensitive to cisplatin and etoposide than were the lung tumor cells from the RPPt-Cks1N45R KI mice. The RPPt lung tumor cells were also more sensitive to growth inhibition by the SCFSkp2/Cks1 inhibitors C1 and pevonedistat and the CDK1/2/5/9 inhibitor dinaciclib... These findings are consistent with the hypothesis that the Rb1/Trp53-deficient SCLC neuroendocrine phenotype is not a fixed feature but can vary with the presence of other oncogenic drivers, and document SCFSkp2/Cks1 as one such driver. This could reflect an early, deterministic lineage redirection toward a YAP1-high, SMARCA4-intact, non-neuroendocrine phenotype. SCFSkp2/Cks1 mediates lung cancer heterogeneity, plasticity and sensitivity to standard cytotoxic and targeted drugs."

Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • ASCL1 • CDK1 • KRT5 • PTEN • RB1 • SKP2 • SMARCA4 • SOX2 • TP63 • YAP1

Targeting CDK1/2-driven mechanisms of resistance to BRAF and EGFR inhibition in BRAF(V600E) colorectal cancer restores therapeutic response (AACR 2024) - "We validated these findings using multiplex immuno-fluorescence in residual tumors, protein/gene expression profile of tissues and cell lines (e.g., upregulation of Cyclins and CDC25s), and cell viability assay using dinaciclib, a CDK1/2 inhibitor. When tumors progress on SOC BRAFi + EGFRi, a therapeutic window remains open to switch to a CDK1/2i-containing regimen and restore cancer control."

Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • CDK1 • CDK2 • GNRP

CDK9 inhibition enhances apoptosis of TP53 mutated AML when combined with standard chemotherapy (AACR 2025) - "Here we test dinaciclib, a multi-CDK and potent CDK9 inhibitor, alone and with azacitidine and venetoclax to demonstrate that CDK9 inhibition as monotherapy and in combination leads to apoptosis in TP53 mutated AML. To determine the effect of inhibiting CDK9 on the cytotoxicity of AML and normal cells, we treated p53 mutated AML cell lines (THP1, NOMO1, and U937), wild type (WT) p53 AML cell lines (MV4-11 and HL-60) and peripheral blood mononuclear cells (PBMCs) from healthy donors with azacitidine, venetoclax, and dinaciclib. We have shown that the addition of a CDK9 inhibitor to azacitidine and venetoclax results in enhanced cytotoxicity of mutant p53 and WT p53 AML cell lines at low nanomolar concentrations. These results suggest that inhibition of CDK9 sensitizes AML cells independently of TP53, with less pronounced cytotoxicity in normal PBMCs of healthy donors. We plan to further examine the effect of CDK9 inhibition using a highly selective CDK9 inhibitor and..."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ANXA5 • GLI2 • PARP1

Suppressing liver metastasis growth by inducing the endogenous expression of the tumor suppressor miR-34a by small synthetic molecules (AACR 2025) - "However, when validating these compounds, only 6 (AT7519, A-674563, BBI503, PCM0240249, KRIBB and SB273005) out of 9 compounds that were tested -induced miR-34a promoter activation and only 2 (AT7519 and A-674563) out of the 6, also caused miR-34a secretion from HepG2, a human hepatoblastoma cell line. Induction of miR-34a using small synthetic molecules is a novel therapeutic approach to eradicate CRC liver metastasis."

Late-breaking abstract • Breast Cancer • Colorectal Cancer • Hepatoblastoma • Melanoma • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • MIR34A

The use of human small intestinal organoids as a preclinical screening tool to assess gastrointestinal toxicity induced by CDK inhibition (AACR 2025) - "All intestinal lineages were present in the organoids and resembled the frequency of linage observed in vivo.The effect of several clinically available CDKIs, such as Dinaciclib, Palbociclib and Abemaciclib, some of them known to induce GI toxicity were assessed. Whereas Palbociclib was the least toxic compound within the human organoid assay, reflecting clinical data that shows the lowest incidence of severe diarrhea.We conclude that organoids are a predictive preclinical model that can be used to identify potential on-target, off-tissue GI toxicities induced by novel therapeutics such as CDKIs. Toxicity and mechanism of action (MOA) can all be addressed in vitro to potentially reduce in vivo experimentation."

Preclinical • Hematological Malignancies • Oncology

Discovering novel ALK-lung carcinoma therapeutic strategies by identifying combinations with Alectinib from ALK-positive lung carcinoma cell lines (AACR 2024) - "Cells were characterized by bulk-RNAseq, bulk-DNA seq, Reverse-phase protein array, and Mass spectrometry to identify perturbed RNA pathways, DNA mutations, and proteome alterations. In this study, we present for the first time, a group of compounds, such as Gilteritinib, Trametinib, Dinaciclib, WYE-125132, Cenisertib, SN-38 which exhibit the capacity to induce cytotoxic effects in ALK-positive lung cancer cells, when combined with Alectinib. Through the integration of different multiomic approaches on five ALK-positive lung cancer cell lines, we have pinpointed a novel role of MAPK, CDK, and mTOR, pathways and their regulators, as a promising avenue for advancing treatment strategies for ALK-positive lung cancer. These findings, along with the identification of several other significant targetable elements illustrate a new approach towards the discovery of new drug combinations and targetable pathways to tackle ALK TKI resistance in ALK-positive patients before it..."

Preclinical • Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • KRAS • STAT3

Inhibition of pyrimidine synthesis and the cell cycle in mesothelioma (AACR 2025) - "BAY2402234 is an extremely potent inhibitor of cell growth in multiple mesothelioma cell lines and 59-1,881 times more potent than brequinar; 2) BAY2402234 and dinaciclib act synergistically, suggesting an interaction between pyrimidine biosynthesis and one or more of the following CDKs: CDK1, CDK2, CDK5, and/or CDK9; and 3) BAY2402234 results in increased PD-L1 expression and increased cytokine pathway mRNA expression, suggesting the potential for enhancement of immune checkpoint blockade."

IO biomarker • Mesothelioma • Oncology • Solid Tumor • CCNA1 • CCND1 • CDK1 • CDK2 • CDK9 • CDKN1A • PD-L1

High-throughput drug repositioning identifies dinaciclib as a potent osteosarcoma inhibitor (AACR 2025) - "This study identifies Dinaciclib as a potent inhibitor of osteosarcoma, with additive cytotoxicity when combined with the clinically relevant Gemcitabine+Docetaxel regimen. These findings, coupled with prior evidence of Dinaciclib's efficacy in reducing metastatic burden in OS patient-derived xenograft models, highlight its potential as part of a triple combination therapy. This research underscores the value of high-throughput drug repurposing in identifying innovative treatment strategies for osteosarcoma and supports further preclinical and clinical evaluation of Dinaciclib to improve outcomes for patients with metastatic or treatment-resistant disease."

Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CDK1

Familial CTR9 mutation reprograms Wilms Tumor cells to a blastemal state and confers vulnerability to CDK9 inhibition (AACR-Kidney 2026) - "Cell viability assays demonstrated that CTR9Δexon9 cells were more sensitive to selective CDK9 inhibitors, including NVP-2, MC180295, and Enitociclib, while no differences were observed with pan-CDK inhibitors, Dinaciclib, indicating specific vulnerability to CDK9-targeted therapy. Together, our study uncovered that CTR9Δexon9 mutation causes aberrant activation of stem/blastemal genes and promotes CDK9/ RNAPII-mediated elongation, leading to a less differentiated, blastemal-like WT phenotype. The increased vulnerability of CTR9Δexon9 cells to selective CDK9 inhibitors provides a strong rationale for developing CDK9-targeted therapies as precision treatments for children with CTR9 mutations and aggressive, blastema-like Wilms tumors."

Tumor cell • Nephrology • Oncology • Solid Tumor • Wilms Tumor • NCAM1 • PAF1

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

Dinaciclib reduces MCL-1 levels and triggers apoptosis in adult T-cell leukemia/lymphoma. (PubMed, Eur J Pharmacol) - "The anti-tumor effects of dinaciclib were confirmed in an in vivo xenograft model. Overall, this study demonstrates that dinaciclib effectively targets ATL cells by inducing MCL-1 deregulation and promoting apoptotic cell death."

Journal • Adult T-Cell Leukemia-Lymphoma • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CASP3 • CDK1 • CDK2 • CDK9 • MCL1

Unveiling the mechanistic link between peroxiredoxin inhibition and ferroptosis-like cell death induced by Dinaciclib in Entamoeba histolytica. (PubMed, Int J Biol Macromol) - "In contrast, the well-established ferroptosis inducer RSL3 did not induce lipid peroxidation but instead upregulated EhPrx expression, suggesting an adaptive defense mechanism against indirect oxidative stress. Collectively, our results suggest that targeting EhPrx overwhelms the parasite's primary redox defense, leading to iron-driven oxidative cell death. Thus, this study identifies EhPrx as an exploitable target and proposes a distinct mechanism that triggers ferroptosis-like death in E. histolytica."

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