spiruchostatin A (OBP-801) / Astellas, Oncolys BioPharma - LARVOL DELTA

Pluripotent epigenetic regulator OBP-801 attenuates fibrosis and maintains lower intraocular pressure in a rabbit PRESERFLO MicroShunt surgery model. (PubMed, Sci Rep) - "This study involved 19 Japanese white rabbits that underwent PMS in the right eye, with those eyes divided into 3 groups: (1) intraoperative subconjunctival injection of 0.02% mitomycin-C (MMC) (n = 6), (2) postoperative instillation of 100 nM OBP eye drops (n = 7), or (3) a balanced salt solution (BSS) control (n = 6). A lower postoperative IOP was maintained in the OBP-group eyes, and at 12 weeks postoperative, the IOP was significantly lower in that group than in the BSS and MMC groups (p < 0.01). OBP-treated eyes showed no adverse effects and reduced levels of alpha-smooth muscle actin and collagen deposition, thus suggesting that OBP is a promising candidate for improving surgical outcomes post PMS."

Journal • Preclinical • Fibrosis • Glaucoma • Immunology • Ophthalmology

Anticancer efficacy of Spiruchostatin A: current insights into histone deacetylase inhibition and oncologic applications. (PubMed, Eur J Med Res) - "Future research is warranted to elucidate detailed molecular mechanisms and to develop biomarkers for predicting treatment response. Comprehensive longitudinal clinical studies are also critical to establish Spiruchostatin A's role within the broader oncological therapeutic regimen, along with the exploration of its analogs for improved therapeutic outcomes."

Journal • Review • Oncology

The Novel HDAC Inhibitor OBP-801 Promotes MHC Class I Presentation Through LMP2 Upregulation, Enhancing the PD-1-Targeting Therapy in Clear Cell Renal Cell Carcinoma. (PubMed, Cancers (Basel)) - "Our results demonstrate that OBP-801 promotes MHC class I presentation through LMP2 upregulation in tumor cells and thereby potentiates PD-1-targeting therapy. These data suggest that the combination of OBP-801 and anti-PD-1 treatment is a promising therapeutic strategy for ccRCC."

IO biomarker • Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD3E • CD8 • PTPRC

Effect of epigenetic regulator OBP-801 on filtering blebs after PRESERFLO® MicroShunt implantation in rabbit eyes (ARVO 2023) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Preclinical • Glaucoma • Ophthalmology

"RB-reactivator screening" as a novel cell-based assay for discoveries of molecular targeting agents including the first-in-class MEK inhibitor trametinib (trade name: Mekinist). (PubMed, Pharmacol Ther) - "Using the screening systems for agents that up-regulate the expression of p15, p27, and p21, we discovered the novel MEK inhibitor trametinib, the novel RAF/MEK inhibitor CH5126766/RO5126766/VS-6766, and the histone deacetylase inhibitor YM753/OBP-801, respectively...The combination of trametinib and the BRAF inhibitor dabrafenib was approved for advanced BRAF mutant melanoma in the USA, EU, Japan, and many other countries...In 2018, this combination was also approved for locally advanced or metastatic BRAF V600-mutant anaplastic thyroid cancer in the USA after it had been granted Breakthrough Therapy Designation by the FDA. I describe here the characterization of our original screening system, RB-reactivator screening, by which these three molecular-targeting agents that advanced into clinical trials were identified."

Journal • Review • Endocrine Cancer • Eye Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Retinal Disorders • Retinoblastoma • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • CDKN1A

The histone deacetylase inhibitor OBP-801 has in vitro/in vivo anti-neuroblastoma activity. (PubMed, Pediatr Int) - "Overall, OBP-801 induces M-phase arrest and apoptosis in neuroblastoma cells via mitotic catastrophe. Our results indicate that OBP-801 is a promising therapeutic agent with fewer adverse effects for patients with neuroblastoma."

Epigenetic controller • Journal • Preclinical • Neuroblastoma • Oncology • Solid Tumor • ANXA5 • CDKN1A • MYCN

Phase Ia dose escalation study of OBP-801, a cyclic depsipeptide class I histone deacetylase inhibitor, in patients with advanced solid tumors. (PubMed, Invest New Drugs) - P1a | "Conclusion Further investigations of the OBP-801 1.0 mg/m dose will be needed to better understand the efficacy of the agent, either alone or in combination. Trial registration: NCT02414516 (ClinicalTrials.gov) registered on April 10, 2015."

Clinical • Epigenetic controller • Journal • P1 data • Dyslipidemia • Fatigue • Hematological Disorders • Hypertriglyceridemia • Oncology • Pain • Solid Tumor

Pluripotent epigenetic regulator OBP-801 maintains filtering blebs in glaucoma filtration surgery model. (PubMed, Sci Rep) - "OBP maintained the long-lived bleb without scar formation, and IOP was lower at 30 postoperative days compared with the vehicle control group. These findings suggest that OBP is an effective and useful candidate low-molecular-weight agent for improving wound healing and surgical outcomes in a rabbit model of GFS."

Journal • Fibrosis • Glaucoma • Immunology • Ophthalmology • MMP2 • SERPINH1

Histone deacetylase inhibitor OBP‑801 and amrubicin synergistically inhibit the growth of squamous cell lung carcinoma by inducing mitochondrial ASK1‑dependent apoptosis. (PubMed, Int J Oncol) - "Moreover, mouse xenograft experiments using human H520 SQCLC cells revealed that the co‑treatment potently suppressed tumor growth in vivo. These results suggested that a combined treatment with OBP‑801 and amrubicin may have potential as a therapeutic strategy for SQCLC."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

The novel histone deacetylase inhibitor OBP-801 induces apoptosis in rhabdoid tumors by releasing the silencing of NOXA. (PubMed, Mol Cancer Ther) - "In conclusion, OBP-801 induces apoptosis in RT cells by epigenetically releasing the silencing of NOXA, which is a key mediator of RT apoptosis. The epigenetic approach for NOXA silencing with OBP-801 is promising for RT treatment."

Journal • Oncology • Rhabdoid Tumor • Sarcoma • CASP3 • INI-1 • PMAIP1 • SMARCA4 • TP53