CKD-506 / Chong Kun Dang - LARVOL DELTA

CKD -506, a New Histone Deacetylase 6 Inhibitor, Suppresses Immune Cells and Restores Intestinal Epithelial Function (IMKASID 2024) - "Results : TNF-α secretion, a pivotal pro-inflammatory mediator in IBD, of LPS-triggered PBMCs was markedly decreased by CKD-506 treatment in a dose-dependent manner and to a greater extent than by tofacitinib or tubastatin A treatment. Caco-2 cells treated with CKD-506 showed a significant reduction of barrier permeability in a dose-dependent manner. Conclusion : The present study demonstrated that CKD-506 has anti-inflammatory effects on PBMCs and CD4+ T cells and improved gut barrier function, indicating its potential as a promising and competent candidate for small-molecule medicine for IBD treatment."

Epigenetic controller • Immune cell • Chronic Kidney Disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • CD4 • CDH1 • TNFA

[Exclusive] Chong Kun Dang, selection and focus on new drug research and developmen Pipeline Tuning [Google translation] (Money Today Network (MTN)) - "Chong Kun Dang recently started adjusting its new drug pipeline to focus on new drug R&D capabilities....It was preparing for phase 2 clinical trials in Europe as an indication for idiopathic pulmonary fibrosis (IPF), and submitted data to the U.S. Food and Drug Administration (FDA) in August of last year and applied for a pre-indication plan (Pre-IND meeting). Depending on the outcome of the meeting, it was planned to decide whether to proceed with phase 2 clinical trials in the US."

Trial status • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease

CKD-506, a new histone deacetylase 6 inhibitor, suppresses immune cells and restores intestinal epithelial function (ECCO-IBD 2023) - "+ Results TNF-α secretion, a pivotal pro-inflammatory mediator in IBD, of LPS-triggered PBMCs was markedly decreased by CKD-506 treatment in a dose-dependent manner and to a greater extent than by tofacitinib or tubastatin A treatment. Caco-2 cells treated with CKD-506 showed a significant reduction of barrier permeability in a dose-dependent manner. Conclusion The present study demonstrated that CKD-506 has anti-inflammatory effects on PBMCs and CD4+ T cells and improved gut barrier function, indicating its potential as a promising and competent candidate for small-molecule medicine for IBD treatment."

Epigenetic controller • Immune cell • Immunology • Inflammation • Inflammatory Bowel Disease • CD4 • CDH1 • TNFA

Novel Histone Deacetylase 6 Inhibitor Confers Anti-inflammatory Effects and Enhances Gut Barrier Function. (PubMed, Gut Liver) - "Secretion of TNF-α, a pivotal pro-inflammatory mediator in IBD, by lipopolysaccharide-triggered PBMCs was markedly decreased by CKD-506 treatment in a dose-dependent manner and to a greater extent than by tofacitinib or tubastatin A treatment. Caco-2 cells treated with CKD-506 showed a significant reduction in barrier permeability in a dose-dependent manner. The present study demonstrated that CKD-506 has anti-inflammatory effects on PBMCs and CD4 T cells and improves gut barrier function, suggesting its potential as a small-molecule therapeutic option for IBD."

Epigenetic controller • Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • CD4 • CDH1 • TNFA

CKD-506 Drug-Drug Interaction Study in Healthy Male Subjects (clinicaltrials.gov) - P1 | N=17 | Completed | Sponsor: Chong Kun Dang Pharmaceutical | Recruiting ➔ Completed

Trial completion

CKD-506, a Selective HDAC6 Inhibitor, Is a First-in-Class Drug Candidate for the Treatment of Idiopathic Pulmonary Fibrosis (IPF) (ATS 2022) - "Rationale: Although Nintendanib and Pirfenidone are the current standard of cares for IPF, the medical needs for new therapeutic agent is still very high due to their significant safety issues...In the current study, we tried to evaluate the efficacy of CKD-506 in IPF models. To evaluate the efficacy of CKD-506, we used IPF patient’s lung sample and bleomycin-induced pulmonary fibrosis mice model... In this study, we provided the evidence that CKD-506 has strong anti-fibrotic efficacy by inhibiting the phosphorylation of SMAD2/3 both in vitro and in vivo models. Taken together, these results indicate that CKD-506 can be a novel therapeutic agent for IPF treatment. We completed phase I study of CKD-506 for healthy subjects and will initiate Phase II study in the first half of 2022."

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • HDAC6 • SMAD3 • TGFB1

CKD-506 Drug-Drug Interaction Study in Healthy Male Subjects (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Chong Kun Dang Pharmaceutical

New P1 trial

CKD-506: A novel HDAC6-selective inhibitor that exerts therapeutic effects in a rodent model of multiple sclerosis. (PubMed, Sci Rep) - "Disease exacerbation was not observed when fingolimod was changed to CKD-506 from day 15 post-EAE induction. In conclusion, CKD-506 exerts therapeutic effects by regulating T cell- and macrophage-mediated peripheral immune responses and strengthening BBB integrity. Our results suggest that CKD-506 is a potential therapeutic agent for MS."

Journal • Preclinical • CNS Disorders • Depression • Immunology • Multiple Sclerosis • Psychiatry • Solid Tumor • IFNG • IL17A • PTPRC

Therapeutic potential of CKD-506, a novel selective histone deacetylase 6 inhibitor, in a murine model of rheumatoid arthritis. (PubMed, Arthritis Res Ther) - "The novel HDAC6 inhibitor CKD-506 suppresses inflammatory responses by monocytes/macrophages, improves Treg function, and ameliorates arthritis severity in a murine model of RA. Thus, CKD-506 might be a novel and effective treatment option for RA."

Journal • Preclinical • Immunology • Rheumatoid Arthritis • Rheumatology • CXCL8 • IL6 • MMP1 • MMP3

CKD-506, a selective histone deacetylase (HDAC) 6 inhibitor, ameliorates colitis through regulation of NF-kB and AP-1 signalling pathway (ECCO-IBD 2020) - "For the efficacy test of CKD-506, we used DSS-, TNBS-, Piroxicam (IL-10−/−)-, and adaptive T-cell transfer (RAG1−/−)-mediated colitis animal models. In promoter assay, HDAC6 overexpression highly induced NF-kB and AP-1 activity and CKD-506 strongly and dose-dependently inhibited both signalling pathways.Conclusion These data provide insight that CKD-506, a selective HDAC6 inhibitor, has anti-inflammatory and anti-colitis effects through regulation of NF-kB and AP-1 signalling pathway. Therefore, CKD-506 may provide beneficial effects in patients with Crohn’s disease and ulcerative colitis."

IL10

Novel Histone Deacetylase 6 Inhibitor CKD-506 Inhibits NF-κB Signaling in Intestinal Epithelial Cells and Macrophages and Ameliorates Acute and Chronic Murine Colitis. (PubMed, Inflamm Bowel Dis) - "CKD-506 blocked NF-κB signaling in IECs and macrophages and ameliorated experimental acute and chronic murine colitis models, which suggests that CKD-506 is a promising candidate for inflammatory bowel disease treatment as a small molecular medicine."

Journal • Preclinical • CXCL8 • IL10 • IL6

CKD-506, a novel HDAC6-selective inhibitor, improves renal outcomes and survival in a mouse model of systemic lupus erythematosus. (PubMed, Sci Rep) - "CKD-506 also significantly reduced IFN-γ, IL-1β, IL-4, IL-6, IP-10, MCP-1, and CCL4 levels in kidney. CKD-506 decreased the production of various pro-inflammatory cytokines and chemokines in the serum and kidneys, resulting in inhibition of cell migration and suppression of lupus nephritis without adverse effects."

Journal

A Study Evaluating the Efficacy and Safety of CKD-506 in Adult Subjects With Moderate-to-Severe Rheumatoid Arthritis and Inadequate Response to Methotrexate (clinicaltrials.gov) - P2a; N=122; Completed; Sponsor: Chong Kun Dang Pharmaceutical

Biomarker • Clinical • New P2a trial

CKD-506, a Selective Histone Deacetylase (HDAC) 6 Inhibitor, Regulates Inflammatory Responses Through NF-kB and AP-1 Signaling (ACR-ARHP 2019) - "In addition, CKD-506 with methotrexate exhibited better anti-inflammatory effects on macrophages with HDAC6 overexpression. CKD-506 inhibits inflammatory mediators such as TNFa, IL-6, IL-1b, ROS, and NADPH oxidase activity in HDAC6 overexpressed cells. This anti-inflammatory activities of CKD-506 are mediated through NF-kB and AP-1."

CKD-506; a novel histone deacetylase (HDAC) 6 inhibitor, ameliorates colitis in various animal models (ECCO-IBD 2019) - "DSS-, TNBS-, Piroxicam (IL-10−/−)-, and adaptive T-cell transfer (RAG1−/−)-mediated colitis animal models were used to check the efficacy of CKD-506. Conclusion These data provide insight that inhibition of HDAC6 by CKD-506 has therapeutic effect in colitis animal models. Therefore, CKD-506 may beneficial effect in patients with Crohn’s disease and ulcerative colitis."

Preclinical