pracinostat (SB939)
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December 02, 2025
Targeting H3K27M protein with inhibitors of histone deacetylases in H3K27-altered diffuse midline gliomas
(SNO 2025)
- "Importantly, we have recently shown that some HDACi (including panobinostat, pracinostat/SB939, vorinostat and entinostat) lead to the reduction in the H3K27M protein levels. We are hoping that our studies may pave the way for new therapeutic strategies for patients with DMGs, aiming at eradication of detrimental H3K27M oncohistone protein. The study is supported by the Sonata Bis-14 grant (2024/54/E/NZ3/00480) awarded by the National Science Centre, Poland."
Epigenetic controller • Brain Cancer • Diffuse Midline Glioma • Glioma • High Grade Glioma • Solid Tumor
November 06, 2025
Targeting H3K27M protein with inhibitors of histone deacetylases in H3K27-altered diffuse midline gliomas
(WFNOS 2025)
- "Importantly, we have recently shown that some HDACi (including panobinostat, pracinostat/SB939, vorinostat and entinostat) lead to the reduction in the H3K27M protein levels. We are hoping that our studies may pave the way for new therapeutic strategies for patients with DMGs, aiming at eradication of detrimental H3K27M oncohistone protein. The study is supported by the Sonata Bis-14 grant (2024/54/E/NZ3/00480) awarded by the National Science Centre, Poland."
Epigenetic controller • Brain Cancer • Diffuse Midline Glioma • Solid Tumor
October 15, 2025
Adverse drug reaction profiles of histone deacetylase inhibitors.
(PubMed, Sci Rep)
- "This study aimed to explore the global observational adverse drug reaction (ADR) profiles of the HDACIs: vorinostat, belinostat, panobinostat, pracinostat, entinostat, romidepsin, bufexamac and sodium phenylbutyrate. Thrombocytopenia observed with vorinostat, panobinostat and romidepsin may stem from dual inhibition of HDAC1 and HDAC2 and their higher volume of distributions (Vd). Despite all HDACIs having a similar mechanism of action, their unique pharmacology and differing physicochemical and pharmacokinetic properties landscape results in varying ADR profiles."
Adverse drug reaction • Journal • CNS Disorders • Depression • Hematological Disorders • Musculoskeletal Diseases • Psychiatry • Thrombocytopenia • HDAC1 • HDAC2 • HDAC3 • HDAC4 • HDAC9
August 28, 2025
Pracinostat inhibits the nefarious biological behavior of pancreatic cancer by targeting the miR-381-3p/MDM2 axis to activate the p53 signaling pathway.
(PubMed, Pathol Res Pract)
- "pracinostat activates the p53 signaling pathway by targeting the miR-381-3p/MDM2 axis, thereby inhibiting the proliferation of pancreatic cancer cells. These findings provide novel insights and potential therapeutic strategies for pancreatic cancer, and may also provide a reference for the treatment of other malignancies."
Journal • Oncology • Pancreatic Cancer • Solid Tumor • Targeted Protein Degradation • MDM2 • MIR381
July 29, 2025
A study investigating different combinations of Cytarabine, Midostaurin, Pracinostat and Venetoclax in elderly patients with Acute Myeloid Leukaemia to extend remission.
(ANZCTR)
- P2 | N=208 | Active, not recruiting | Sponsor: The Australasian Leukaemia and Lymphoma Group | Recruiting ➔ Active, not recruiting
Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Neutropenia • Oncology
May 16, 2025
SINGLE-CELL RNA AND ATAC-SEQ HIGHLIGHTS RAPID ADAPTATION OF MONOSOMY 7 PROGENITOR POPULATIONS TO NOVEL THERAPIES IN AML
(EHA 2025)
- "In preclinical models, including primary AML samples and patient-derived xenografts (PDX) with TP53 mutations or monosomy 7, the combination of venetoclax and an HDAC inhibitor demonstrated enhanced efficacy.We next leveraged samples from a phase I/II clinical trial (ALLG AMLM25 INTERVENE, Chua et al, ASH 2021) which compared a triplet comprising venetoclax, low-dose cytarabine (LDAC), and an HDACi pracinostat to venetoclax-LDAC doublet in patients with adverse cytogenetic risk AML. We demonstrate that monosomy 7 is a marker of poor overall survival in patients receiving intensive or venetoclax-based therapy. Rapid emergence of adaptive resistance in leukemic progenitors to novel therapies highlights the need for new approaches in order to improves in this challenging patient subgroup."
Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • TP53
May 14, 2025
HISTONE DEACETYLASE INHIBITOR VORINOSTAT INDUCES R-LOOP-DEPENDENT CHANGES IN CHROMATIN ACCESSIBILITY AND ERYTHROID DIFFERENTIATION IN SF3B1-MUTATED ERYTHROBLASTS.
(MDS 2025)
- "Our aim is to explore R-loop-dependent transcriptional and epigenetic changes in MDS erythropoiesis.MethodsSF3B1MUT, SRSF2MUT and SFWTMDS erythroblasts were derived from BM CD34+progenitors and treated 24h with pan-HDACi (vorinostat, pracinostat) or selective HDAC(I/IV)i (entinostat). The impact of vorinostat on R-loop dynamics suggests an epigenetic regulation by histone acetylation of R-loop-dependent gene transcription. This may suggest testing low-dose vorinostat in transfusion-dependent SF3B1MUT-MDS patients resistant or non-eligible to luspatercept or ESAs."
Epigenetic controller • Hematological Malignancies • Myelodysplastic Syndrome • CD34 • CDKN1A • GATA1 • SF3B1 • SRSF2
March 26, 2025
Overcoming resistance in mCRPC: drug discovery using PDX models and high-throughput drug screening
(AACR 2025)
- "Within active compounds we find selective kinase inhibitors (BRAF, JAK2, AKT, FLT3) and histone deacetylase inhibitors (belinostat and pracinostat). In summary, we leveraged RNAseq data from mCRPC patients and PDX models and performed a high-throughput drug screen in PDX-derived organoid models to identify potential drugs that could overcome abiraterone-resistance in lethal advanced prostate cancer. These data highlight potential drug combinations or subsequent therapeutic strategies for these patients.Summary of drug screening in PDX-derived organoidsAbiraterone SensitiveAbiraterone Resistant-1Abiraterone Resistant-2Active (IC5025µM)251435Number of total drugs tested493249"
Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRAF • FLT3
March 27, 2025
High throughput drug screening on head and neck cancer organoids reveals novel therapeutic strategies
(COSM 2025)
- "Of these, 4 exhibited ≥ 50% selectivity for tumor tissue compared to normal (pracinostat, tanespimycin, SB-743921, and mocetinostat). High-throughput drug screening across eight normal, dysplastic, and HNSCC PDOs revealed protein and epigenetic targeting drugs to have the most proportional hits. Specifically, HSP90 and HDAC inhibitors were most effective within their drug class. Pending dose response experiments and validation across a larger cohort, these results provide potential novel protein and epigenetic targeting strategies as promising approaches in HNSCC."
Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CDC37 • HSP90AA1
March 28, 2025
Genomic and metabolomic insights into the antimicrobial compounds and plant growth-promoting potential of Bacillus velezensis B115.
(PubMed, Sci Rep)
- "Utilizing LC-MS/MS technologies, 2318 metabolites were detected in the fermentation broth of B. velezensis B115, encompassing compounds such as Corynebactin, Gamabufotalin, Pracinostat, Indoleacetic acid, (8)-Gingerol, Luteolin, Liquiritigenin, and other metabolites with antimicrobial, growth-promoting, antioxidant, and antitumor properties. By exploring secondary metabolite-related genes and predicting potential secondary metabolites from the B115 genome based on the whole-genome sequence results, we further elucidate the genomic basis for its ability to promote plant growth and inhibit pathogen activity."
Journal • Oncology
March 28, 2025
Effects of SB939 are mediated by STAT3 to inhibit breast cancer cell metastasis-related genes.
(PubMed, Oncol Lett)
- "Furthermore, MMP2 exhibits crosstalk STAT3 to induce metastasis of breast cancer cells. To conclude, SB939 may be used as a small molecule compound for the clinical treatment of breast cancer."
Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • FN1 • MMP2 • STAT3
March 27, 2025
High throughput drug screening on head and neck cancer organoids reveals novel therapeutic strategies
(AHNS-COSM 2025)
- "Of these, 4 exhibited ≥ 50% selectivity for tumor tissue compared to normal (pracinostat, tanespimycin, SB-743921, and mocetinostat). High-throughput drug screening across eight normal, dysplastic, and HNSCC PDOs revealed protein and epigenetic targeting drugs to have the most proportional hits. Specifically, HSP90 and HDAC inhibitors were most effective within their drug class. Pending dose response experiments and validation across a larger cohort, these results provide potential novel protein and epigenetic targeting strategies as promising approaches in HNSCC."
Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CDC37 • HSP90AA1
December 17, 2024
HDAC Inhibitors Can Enhance Radiosensitivity of Head and Neck Cancer Cells Through Suppressing DNA Repair.
(PubMed, Cancers (Basel))
- " We identified that histone deacetylases (HDACs) were prominent candidates, and subsequently identified that the HDAC inhibitors mocetinostat and pracinostat, as well as the combined HDAC-epidermal growth factor receptor inhibitor CUDC-101, were effective at radiosensitising cell models of HNSCC (FaDu, A253, UMSCC11b) through their impact on both spheroid growth and clonogenic survival assays. We also demonstrated that this combinatorial strategy leads to inhibition of the repair of DNA double-strand breaks through the neutral comet assay and γH2AX foci analysis using immunofluorescence microscopy, providing a mechanism of action through which HDAC inhibition functions in HNSCC radiosensitisation. We believe that this approach should be further investigated in preclinical models, in order to realise the full therapeutic potential of HDAC inhibition for the radiosensitisation of HNSCC, eventually leading to improved patient treatment efficacy and outcomes."
Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR
November 25, 2024
Identification of key genes and drug recommendations in diffuse large B-cell lymphoma based on analysis of glutathione-related genes.
(PubMed, Cytogenet Genome Res)
- "The relationship between DLBCL and glutathione-related genes was uncovered by our research, and six glutathione genes were linked to DLBCL. These genes might be used as diagnostic biomarkers or targets for treatment for DLBCL patients."
Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BRCA1 • KPNA2
October 11, 2024
Three novel epigenetic-modifying compounds identified as HIV latency-reversing agents in Ghana
(ASTMH 2024)
- "The lead compounds were further screened in CD4+ T cells of four individuals living with HIV on suppressive ART.We identified five positive hits (MC1568, Abexinostat, Pracinostat, EPZ2015666, CXC6258-HCL) from the J.LAT 10.6 cell culture system with GFP-positive cells (20-91%). These compounds effectively reactivated latent HIV-1 in vitro and induced HIV expression ex vivo. Our findings suggest that these LRAs hold promise for reactivating latent HIV in individuals living with the virus."
Human Immunodeficiency Virus • Infectious Disease • CD4
September 26, 2024
Low dose dual epigenetic therapy utilizing hypomethylating agents and HDAC inhibitors prolong survival in an orthotopic PDAC model and alter the tumor microenvironment.
(AACRPanCa 2024)
- "Background: We have previously studied the effect of hypomethylating agent Decitabine (5- aza-dC; DAC) on pancreatic cancer using the KPC model (KrasG12D/+; Trp53R172H/+; Pdx1- Cre) and observed increased CD4+/CD8+ TILs, greater PD1 expression and slowed tumor growth with increased tumor necrosis...Three HDAC inhibitors were chosen for in vivo testing, Domatinostat, Pracinostat and Entinostat... Our results show that the combination of hypomethylating agent plus HDAC inhibitor has several beneficial effects on the tumor immune response in PDAC. HDAC inhibitors specifically reduce the suppressive myeloid cell population we previously identified after DAC therapy. The combination of dual low dose epigenetic therapy using a hypomethylating agent plus HDAC inhibitor followed by αPD1 results in significant survival benefit in the orthotopic KPC model."
Biomarker • IO biomarker • Tumor microenvironment • Gastrointestinal Cancer • Gene Therapies • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CD4 • CD8 • KRAS • PDX1
March 15, 2024
LOW DOSE DOUBLE EPIGENETIC THERAPY IMPROVES IMMUNOTHERAPY RESPONSE AND PROLONGS SURVIVAL IN PANCREATIC CANCER.
(DDW 2024)
- "We previously showed, using the KPC (Kras LSL G12D/+; p53 r172H/+; Pdx1-Cre) mouse model of pancreatic cancer (PDAC), that sequential treatment with the DNA hypomethylating agent (HMA) decitabine (DAC) followed by aPD-1 initially enhanced anti-tumor effects, yet tumors developed resistance linked to a unique M2-polarized Chil3+ myeloid subtype...We then evaluated four different HDAC inhibitors with reported immunomodulatory effects and non-overlapping HDAC isoform specificities: Romidepsin (RM), Domatinostat (DM), Pracinostat (PR) and Entinostat (EN)...Our findings identify a functionally immune suppressive HMA specific myeloid effect. The addition of a second epigenetic agent enhances the therapeutic efficacy resulting in prolonged survival and reverses the suppressive myeloid cell related effects of DAC + aPD1."
IO biomarker • Gastrointestinal Cancer • Gene Therapies • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CD8 • KRAS • PDX1
May 18, 2024
Induction of indoleamine 2,3-dioxygenase 1 expression in neurons of the central nervous system through inhibition of histone deacetylases blocks the progression of experimental autoimmune encephalomyelitis.
(PubMed, Int Immunopharmacol)
- "Overall, our results suggest that IDO1 tryptophan metabolites produced by neuronal cells may act on AHR in pathogenic CD4+ T cells in a paracrine fashion in the CNS and that the specific induction of IDO1 expression in neurons at disease-afflicted sites can be considered a therapeutic approach to block the progression of multiple sclerosis without affecting systemic immunity."
Epigenetic controller • IO biomarker • Journal • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis • Solid Tumor • CD4 • IDO1 • IL6 • STAT3
March 06, 2024
Increasing the therapeutic vulnerability of heterogenous cell phenotypes within prostate cancer
(AACR 2024)
- "Tested compounds with differential sensitivity between aggressive and non-aggressive cells were those inhibiting histone deacetylase (vorinostat, fimepinostat, and pracinostat), proteasomes (bortezomib, delanzomib, ixazomib), topoisomerases (gimatecan and daunorubicin), and other compounds identified independently by us targeting nicotinamide phosphoribosyl transferase (FK866) and DNA (bleomycin). Funding was provided by the University of Arizona Cancer Center (NCI-P30 CA23074 and NCI-R01 CA159406) and by the Partnership in Native American Cancer Prevention at the University of Arizona (U54CA143924) and Northern Arizona University (U54CA143925). Collaborators at NCATS were supported by the intramural research program."
Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CDH1 • CLDN4 • CLDN7 • KRT6A • ZEB1
March 19, 2024
Pracinostat combined with azacitidine in newly diagnosed adult acute myeloid leukemia (AML) patients unfit for standard induction chemotherapy: PRIMULA phase III study.
(PubMed, Leuk Res)
- P3 | "There was no significant difference between treatments in secondary efficacy endpoints, reflecting a lack of clinical response. This study did not show a benefit of adding pracinostat to AZA in elderly patients unfit for IC."
Journal • P3 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation
March 12, 2024
Discovery of novel anaplastic lymphoma kinase (ALK) and histone deacetylase (HDAC) dual inhibitors exhibiting antiproliferative activity against non-small cell lung cancer.
(PubMed, J Enzyme Inhib Med Chem)
- "A series of novel benzimidazole derivatives were designed and synthesised based on the structures of reported oral available ALK inhibitor and HDAC inhibitor, pracinostat...Compound 3b also inhibited various ALK mutants known to be involved in crizotinib resistance, including mutant L1196M (IC50, 4.9 nM)...At 20 mg/kg, 3b inhibited tumour growth by 85% yet had a negligible effect on mean body weight. These results suggest a attracting route for the further research and optimisation of dual ALK/HDAC inhibitors."
Epigenetic controller • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK
February 02, 2024
H2A.Z histone variants facilitate HDACi-dependent removal of H3.3K27M mutant protein in pediatric high-grade glioma cells.
(PubMed, Cell Rep)
- "We discover that the SB939-mediated H3.3K27M loss is partially blocked by a lysosomal inhibitor, chloroquine. We discover a mechanism showing that HDAC inhibition in DIPG leads to pharmacological modulation of the oncogenic H3.3K27M protein levels. These findings show the possibility of directly targeting the H3.3K27M oncohistone."
Journal • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Pediatrics • Solid Tumor
January 12, 2024
ALDH1A3 contributes to tumorigenesis in high-grade serous ovarian cancer by epigenetic modification.
(PubMed, Cell Signal)
- "Knockdown of ALDH1A3 prevented HGSOC tumorigenesis and enhanced cell sensitivity to paclitaxel or cisplatin...Treatment of exogenous acetate with NaOAc or inhibition of histone deacetylase with Pracinostat increased H3K27ac and PITX1 levels. CHIP assay demonstrated a significant enrichment of H3K27ac at the PITX1 promoter, and ALDH1A3 knockdown reduced the binding between H3K27ac and PITX1. Taken together, our data suggest that ALDH1A3, transcriptional activated by HIF-1α, promotes tumorigenesis and decreases chemosensitivity by increasing H3K27ac of PITX1 promoter in HGSOC."
Journal • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • ALDH1A3 • HIF1A
November 30, 2023
Histone deacetylase inhibitor pracinostat suppresses colorectal cancer by inducing CDK5-Drp1 signaling-mediated peripheral mitofission.
(PubMed, J Pharm Anal)
- "Mechanistically, pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor (MFF) to mitochondrial fission 1 protein (FIS1). Thus, our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells, which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment."
Epigenetic controller • Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor
September 28, 2023
The Comprehensive Analysis of m6A-Associated Anoikis Genes in Low-Grade Gliomas.
(PubMed, Brain Sci)
- "AT.9283, EXEL.2280, Gilteritinib, and Pracinostat had the largest correlation (absolute value) with a risk score. Four risk model genes (mRNAs), 12 miRNAs, and 21 lncRNAs formed an mRNA-miRNA-lncRNA network, containing HOXA10-hsa-miR-129-5p-LINC00689 and KIF18A-hsa-miR-221-3p-DANCR. Through bioinformatics, we constructed a prognostic model of m6A-associated anoikis genes in LGG, providing new ideas for research related to the prognosis and treatment of LGG."
Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • ANXA5 • BRCA1 • CD4 • DANCR • KIF18A • MIR129 • MIR221
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