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

HDAC and CDK inhibitor combinations suppress neutrophil activation in myeloma (ASH 2025) - "To overcome translational barriers associated with dinaciclib and entinostat, we evaluated next-generation agents: KB0742, a selective and orally bioavailable CDK9 inhibitor, in combination with quisinostat or zabadinostat , two potent HDAC inhibitors with more favorable pharmacokinetic and safety profiles. These transcriptional changes, accompanied by increased re-expression of tumor suppressors (e.g.,p16) and TGFβ/SMAD signaling components, would predict reprogramming of an anti-inflammatory microenvironment by these combination treatments in myeloma. These findings point to a promising but underdeveloped therapeutic avenue whereby suppressing neutrophil-driven inflammation enhances anti-myeloma immunity."

Hematological Malignancies • Multiple Myeloma • Smoldering Multiple Myeloma • BCL2L1 • CXCL1 • CXCL8 • IL1A • IL23A • ITGAM • NRAS • SDC1

The transition from myelodysplastic neoplasm to secondary acute myeloid leukemia is revealed by molecular analysis, while functional drug screening demonstrates novel sensitivity patterns with clinical implication (ASH 2025) - "There are only a limited number of agentsthat are FDA approved for treatment of MDS including BCL2 and IDH inhibitors, hypomethylating agents(HMAs), ESAs, luspatercept and imetelstat...For MDS patients, weidentified the most effective agents with the proportion of sensitive samples noted in parentheses:mitoxantrone (100%), olutasidenib (78%), venetoclax (67%), dinaciclib (67%), trametinib (67%), olaparib(56%), GSK3368715 (56%), pacritinib (44%), lenalidomide (44%), fludarabine (55%), tasquinimod (44%),veliparib (44%). For sAML patients, we identified lenalidomide, olutasidenib, GSK3368715 have high DSSsin all tested samples, while fludarabine, fedratinib, tasquinimod, trametinib, veliparib, mitoxantrone andolaparib have high DSSs in 75% of the AML samples...Cancer Research 2024), and our samples included SF3B1 and U2AF1 mutations.Summary This study of the transition of MDS to sAML highlights molecular changes and reveals new drugsensitivity with agents that could be..."

Biomarker • Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • CD34 • FLT3 • JAK2 • NRAS • PTPN11 • SF3B1 • U2AF1

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

Dinaciclib improves treatment response in chemoresistant hepatoblastoma. (PubMed, Sci Rep) - "A HB patient-derived xenograft (PDX) model was treated with placebo, vincristine + irinotecan (VI), dinaciclib, or VI + dinaciclib to evaluate tumor growth and response to therapy. In our PDX model, treatment with VI + dinaciclib resulted in decreased tumor volume, viability and HB cell proliferation. Given these findings, combination treatment with VI and dinaciclib should be investigated further as a treatment for chemoresistant HB."

Journal • Hepatoblastoma • Oncology • Solid Tumor • CDK9

Cdk5 regulates glutamine metabolism in colorectal cancer via the EZH2-GLS1 axis. (PubMed, Cancer Metab) - "Results showed that Dinaciclib treatment suppressed tumor growth in the CRC model, with this inhibitory effect being further potentiated upon combination with glutamine deprivation. These findings not only uncover the intricate interplay between Cdk5, EZH2, and glutamine metabolism in CRC but also offer novel insights into the pathogenic mechanisms of CRC and identify potential therapeutic targets."

Journal • Colorectal Cancer • Oncology • Solid Tumor

Inhibition of Cyclin-Dependent Kinase 9 Rapidly Induces Apoptosis in Acute Lymphoblastic Leukemia and Shows Synergistic Activity with BH3-Mimetics (ASH 2024) - "Using the multi-CDK inhibitor dinaciclib, which targets CDK1, 2, 5 and 9, and the specific CDK9 inhibitor AZD4573, we analyzed the effects of both inhibitors in a series of ALL cell lines (BCP-ALL n=10, T-ALL n=6) and primary, patient-derived xenograft (PDX) samples (BCP-ALL n=15, T-ALL n=9)...Based on this, we investigated combinatorial inhibition of CDK9 (AZD4573) together with inhibitors of BCL-2 or BCL-XL (venetoclax, A-1331852, AZD4320) using dose-response matrix analyses and found enhanced cell death and synergistic activity for both combinations...However, intrinsic insensitivity due to dysbalanced protein levels of pro-survival proteins might limit efficacy. Combining CDK9 inhibition with inhibitors of the anti-apoptotic molecules BCL-2/BCL-XL significantly enhances cell death, thus overcoming insensitivity and providing an effective, novel therapeutic anti-ALL strategy to be further evaluated for clinical application."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • ANXA5 • BCL2L1 • CASP3 • CDK1 • CDK9 • MCL1

CDK9 Inhibition Sensitizes TP53 Mutated AML to Standard Chemotherapy (ASH 2024) - "Here, we combine dinaciclib, a potent CDK9 inhibitor, with standard azacitidine and venetoclax to demonstrate inhibition of CDK9 is an effective approach to inducing apoptosis in TP53 mutated AML.Methods : To determine the effect of inhibiting CDK9 on apoptosis of p53 mutated AML, we treated both p53 mutated AML cell lines, THP1, NOMO1, and U937, and wild type (WT) p53 cell lines, MV4-11 and HL-60, with azacitidine, venetoclax, and dinaciclib, as single-agents and in combination. This action was less pronounced in normal PBMCs. We have ongoing experiments testing this drug combination on normal human CD34+ cells to better determine a therapeutic window to maximize apoptosis in leukemia cells while causing the least cytotoxicity in normal human cells, which should lead to validation studies in vivo."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ANXA5 • BIRC5 • CASP3 • CD34 • GLI2 • MCL1 • PARP1

Regulation of Alternative Splicing in B-Cell ALL By DYRK1A (ASH 2023) - "We also found that indisulam and its analogs, which lead to DCAF15-mediated degradation of RBM39, suppressed the growth of B-ALL cells in vitro and in vivo. Ectopic expression of RBM39 partially rescued the growth inhibition upon dinaciclib and EHT 1610 treatment suggesting downregulation of RBM39 is the key event in drug targeting. Together, our results reveal that DYRK1A controls RNA splicing by regulating the SF3B1-RNA Pol II interaction and that RBM39 is a therapeutic target in B-ALL."

Developmental Disorders • Genetic Disorders • RBM39 • SF3B1 • SRSF2 • STAT3 • UPF1

Characterization and Inhibition of Human Hexokinase Domain Containing Protein 1 Reveals an Enzyme with Unique Catalytic and Regulatory Traits. (PubMed, ACS Chem Biol) - "The hexokinase activity of HKDC1 is also insensitive to Dinaciclib, a pan cyclin-dependent kinase inhibitor that reportedly disrupts the ability of nuclear localized HKDC1 to phosphorylate retinoblastoma-binding protein 5...An HKDC1 variant associated with retinitis pigmentosa, T58M, displays a modest, but statistically significant 2-fold decrease in catalytic efficiency (kcat/Km,glucose) compared to the wild-type enzyme. Together, our results provide a detailed functional characterization of recombinant HKDC1 and set the stage for investigating the link between HKDC1 catalysis and human disease."

Journal • Eye Cancer • Genetic Disorders • Inherited Retinal Dystrophy • Liver Cancer • Ocular Inflammation • Oncology • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa • Retinoblastoma • Solid Tumor • HK1

Interplay of PRMTs and Identification of Biomarkers Through Machine Learning Algorithms in Pan-Cancer, Highlighting PRMT3 as a Biomarker in Pancreatic Cancer. (PubMed, FASEB J) - "Daporinad, dinaciclib, and sepantronium bromide were predicted as potential drugs for the majority of cancer types. Potential biomarkers had been identified that may predict responses to immunotherapy and improve survival outcomes for cancer patients. This study provided a detailed overview of the functional roles, genetic and epigenetic alterations, and prognostic significance of PRMTs in pan-cancer."

Biomarker • IO biomarker • Journal • Pan tumor • Oncology • Pancreatic Cancer • Solid Tumor • PRMT3

Identification of effective cyclin-dependent kinase 3/cyclin E inhibitors using multi-level computational screening and simulation. (PubMed, Comput Biol Med) - "Docking studies identified interactions of the five selected candidates with crucial residues of CDK3. Global reactivity suggested favourable electronic properties for receptor binding. MD simulations, MM-PBSA and ONIOM revealed stable ligand-receptor interactions and favourable binding energetics. Extended 1200ns simulations of the two hits, CID_11212010 and CID_25211747, demonstrated exceptional stability of CID_25211747 with minimal conformational fluctuation. Additional ONIOM calculations reproduced the strong binding affinity of CID_25211747 with CDK3. Collectively, these results nominate CID_25211747 as a promising lead towards the development of effective CDK3 antagonists, offering valuable insight for future drug design."

Journal • Oncology • CDK3

CDK1 drives SOX9-mediated chemotherapeutic resistance in gastric cancer. (PubMed, J Exp Clin Cancer Res) - "This study elucidates the epigenetic and transcriptional mechanisms driving the CDK1-SOX9-BCL-xL axis in gastric cancer chemoresistance. Pharmacological inhibition of CDK1 effectively disrupts this axis, restoring cisplatin sensitivity and suppressing tumor growth in gastric cancer models. The observed synergy between dinaciclib and cisplatin underscores a promising therapeutic strategy to overcome chemoresistance in gastric cancer."

Journal • Gastric Cancer • Oncology • Solid Tumor • BCL2L1 • CDK1 • DNMT1 • MIR145 • SOX9 • TFF1

HDAC and CDK Inhibitor Combinations Synergize in Limiting Myeloma (IMS 2025) - "Further investigation into a combined genetic signature will aid in discovering mechanisms of drug synergy and provide biomarkers for a combined response that may translate to the clinic."

Late-breaking abstract • Hematological Malignancies • Multiple Myeloma • ANXA5 • BCL2L1 • CDK1 • HDAC1 • MYC • SDC1

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 2025 ➔ Aug 2026

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

TP53-Agnostic Lethality through Combined Pan-HDAC and CDK Inhibition in Acute Myeloid Leukemia. (PubMed, Cancer Lett) - "Biochemical profiling showed that CAY10603 is not only HDAC6-selective but also exhibits pan-HDAC activity similar to suberoylanilide hydroxamic acid, enabling dual targeting of transcriptional and cell cycle pathways. In an orthotopic NSG mouse model, dinaciclib + CAY10603 significantly reduced leukemia burden and extended survival without adverse toxicity. By "normalizing" TP53-mutant AML to respond like its wild-type counterpart, this pan-HDAC/multi-CDK blockade offers a TP53-agnostic therapeutic option and warrants clinical evaluation as a strategy that remains effective regardless of baseline allelic status."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CDK2 • CDK4 • CDKN1A • TP53

CDK inhibitors promote neuroblastoma cell differentiation and increase sensitivity to retinoic acid-a promising combination strategy for therapeutic intervention. (PubMed, Cell Death Discov) - "This study investigated three CDKis (abemaciclib, fadraciclib, and dinaciclib) alone or combined with retinoic acid (RA) to assess the effects on morphology, growth, gene expression, and the induction of immunogenic cell death in NB cell lines with (LAN-1 and CHLA-90) and without (CHLA-172) MYCN amplification. CDKi treatments promote NB differentiation via ER stress, with cytotoxicity enhanced by RA co-treatment. This may increase NB immunogenicity and support immunotherapy eligibility."

IO biomarker • Journal • Neuroblastoma • Oncology • Solid Tumor • CALR • CCNE2 • CDK4 • CDKN2A • CRABP2 • MCM4 • MYBL2 • MYCN • ROBO2

Multi-Omics Integration: Predicting Progression and Optimizing Clinical Treatment of Hepatocellular Carcinoma Through Malignant-Cell-Related Genes. (PubMed, Int J Mol Sci) - "Risk stratification based on these signatures revealed distinct therapeutic vulnerabilities: high-risk patients showed increased sensitivity to sorafenib, while low-risk patients exhibited enhanced responses to immunotherapy and transarterial chemoembolization (TACE). Pharmacogenomic analysis with Oncopredict identified four chemotherapeutic agents, including sapitinib and dinaciclib, with risk-dependent efficacy patterns. Furthermore, CRISPR/Cas9-dependency screening prioritized SRSF7 as essential for HCC cell survival, a finding confirmed by the identification of protein-level overexpression in tumors via immunohistochemistry. This multi-omics framework bridges single-cell characterization to clinical decision-making, offering a clinically actionable prognostic system that can be used to optimize therapeutic selection in HCC management."

Biomarker • IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • SRSF7

EFFICACY OF NOVEL TARGETED THERAPIES IN DOWN SYNDROME ACUTE LYMPHOBLASTIC LEUKAEMIA (EHA 2025) - "In vivo assessment showed that treatment with dinaciclib significantly prolonged survival of genetically diverse DS-ALL PDX models. Altogether, we established unique clinically relevant models and identified new actionable targets in DS-ALL. This preclinical pipeline will help to facilitate the translation of the inhibitors with high efficacy and low toxicity into the clinic, to ultimately improve care, quality of life and long-term outcomes for children with DS-ALL."

Clinical • Acute Lymphocytic Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Oncology

High-throughput drug screening of clear cell ovarian cancer organoids reveal vulnerability to proteasome inhibitors and dinaciclib and identify AGR2 as a therapeutic target. (PubMed, Cancer Res Commun) - "ER stress and the UPR are activated in CCC, and proteasome inhibitors disrupt this balance, ultimately leading to cell death. AGR2 may serve as a potential therapeutic target in CCC."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Ovarian Cancer • Ovarian Clear Cell Cancer • Solid Tumor • AGR2

Dinaciclib impairs mRNA splicing: unlocking new vulnerability in merkel cell carcinoma (SID 2025) - "In a preclinical xenograft model of MCC, dinaciclib significantly suppressed tumor growth without adverse effects on body weight or other detectable toxicities. Overall, our study positions dinaciclib as a promising therapeutic candidate for MCC while identifying mRNA splicing inhibition as a novel and targetable pathway in the treatment of this aggressive cancer."

IO biomarker • Genetic Disorders • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • BCL2L1 • CDK1 • MCL1 • XIAP

CDK1-MEDIATED REGULATION OF SOX9 DRIVES CHEMOTHERAPY RESISTANCE IN GASTRIC CANCER (DDW 2025) - "Inhibition of CDK1, through genetic knockdown or the pharmacological agent dinaciclib, reduced SOX9 expression, disrupted BCL-xL activity, and sensitized cisplatin-resistant GC models to chemotherapy. These findings establish the CDK1-SOX9-BCL-xL axis as a key mechanism of chemoresistance in GC, providing a potential therapeutic target. The inclusion of CDK1 inhibitors in treatment strategies offers a promising avenue to enhance efficacy and counteract resistance, providing a brighter outlook for patients with advanced gastric cancer."

Gastric Cancer • Oncology • Solid Tumor • BCL2L1 • CDK1 • DNMT1 • MIR145 • SOX9

EXPLORING THE SYNERGISTIC IMPACT OF DINACICLIB AND AFATINIB AS A NOVEL THERAPEUTIC STRATEGY IN GASTRIC CANCER (DDW 2025) - "The ATP-GLO assay data demonstrated that the combination of Dinaciclib and Afatinib significantly increased cell death in all tested cancer cell lines (AGS, MKN28, MKN45, SNU1, and HGC27) and had no effect on non-cancer cells (MEF), compared to the control (P<0.01). Clonogenic survival assay results indicated that Dinaciclib and Afatinib co-treatment induced significant cell death in AGS and MKN28 cells compared to vehicle-treated cells (P<0.01). The Annexin V apoptosis assay revealed that Dinaciclib/Afatinib co-treatment induced apoptosis by 10-fold in AGS, 5-fold in MKN28, and 50-fold in HGC27 cells relative to vehicle-treated cells (P<0.01)."

Gastric Cancer • Oncology • Solid Tumor • ANXA5 • CASP3 • CDK1

PLK1 and multi-CDKs dual inhibition as a novel approach for the treatment of adrenocortical carcinomas (ESPE-ESE 2025) - "Plogosertib and dinaciclib were the most effective inhibitors in all cell lines, representing interesting novel targeted treatment options for ACC. Moreover, the combination of these drugs showed a synergistic effect, suggesting a potential benefit of using both PLK1i and multi CDKi that need to be further investigated in vivo."

Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • ACACB • CASP3 • CASP7 • CCNB1 • CDK1 • MUC1 • PLK1

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 • Gastric Cancer • Hepatoblastoma • Melanoma • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • MIR34A