^
    5ms
    POPLAR-NF2: Efficacy and Safety of REC-2282 in Patients With Progressive Neurofibromatosis Type 2 (NF2) Mutated Meningiomas (clinicaltrials.gov)
    P2/3, N=89, Recruiting, Recursion Pharmaceuticals Inc.
    Trial completion date • Trial primary completion date
    |
    NF2 (Neurofibromin 2)
    |
    NF2 mutation
    |
    REC-2282
    over2years
    Early phase clinical studies of AR-42, a histone deacetylase inhibitor, for neurofibromatosis type 2-associated vestibular schwannomas and meningiomas. (PubMed, Laryngoscope Investig Otolaryngol)
    A phase 2 study of AR-42 for NF2-associated tumors appears warranted. 1b, 4.
    Clinical • Journal • Epigenetic controller
    |
    NF2 (Neurofibromin 2)
    |
    REC-2282
    over3years
    Targeting DNA damage repair functions of two histone deacetylases, HDAC8 and SIRT6, sensitizes acute myeloid leukemia to NAMPT inhibition. (PubMed, Clin Cancer Res)
    Our findings provide evidence that HDAC8 inhibition- or shSIRT6-induced DNA repair deficiencies are potently synergistic with NAMPT targeting, with minimal toxicity towards normal cells, providing a rationale for a novel-novel combination-based treatment for AML.
    Journal
    |
    PARP1 (Poly(ADP-Ribose) Polymerase 1) • NAMPT (Nicotinamide Phosphoribosyltransferase) • SIRT6 (Sirtuin 6)
    |
    DDR
    |
    padnarsertib (KPT-9274) • REC-2282
    over3years
    FOXA1 Regulation Turns Benzamide HDACi Treatment Effect-Specific in BC, Promoting NIS Gene-Mediated Targeted Radioiodine Therapy. (PubMed, Mol Ther Oncolytics)
    Further, AR-42 and MS-275 treatment shows enhanced NIS expression in an orthotopic breast tumor model. Cerenkov imaging revealed higher accumulation of I in MS-275-treated tumors. Thus, bHDACi-mediated selective enhancement ensuring minimal off-target effect is a step further toward using NIS as a therapeutic target for BC.
    Journal
    |
    FOXA1 (Forkhead Box A1)
    |
    Jingzhuda (entinostat) • REC-2282
    4years
    Heme oxygenase-1 reduces the sensitivity to imatinib through nonselective activation of histone deacetylases in chronic myeloid leukemia. (PubMed, J Cell Physiol)
    Increased expression of HO-1 activated HDACs by inhibiting ROS production. In summary, HO-1, which is involved in the development of drug resistance in CML cells by regulating the expression of HDACs, is probably a novel target for improving CML therapy.
    Journal
    |
    HMOX1 (Heme Oxygenase 1)
    |
    imatinib • REC-2282
    4years
    Design, Synthesis and Evaluation of Novel 3/4-((Substituted benzamidophenoxy)methyl)-N-hydroxybenzamides / propenamides as Histone Deacetylase Inhibitors and Antitumor Agents. (PubMed, Anticancer Agents Med Chem)
    Several compounds of these structural classes have been approved for clinical uses to treat different types of cancer, such as givinostat (ITF2357) and belinostat (PXD-101)...Two new series of N-hydroxybenzamides and N-hydroxypropenamides analogues (4a-j, 6a-j) designed based on the structural features of nexturastat A, AR-42, and PXD-101, were synthesized and evaluated for HDAC inhibitory potency as well as cytotoxicity against three human cancer cell lines (SW620 (colorectal adenocarcinoma), PC3 (prostate adenocarcinoma), and NCI-H23 (adenocarcinoma, non-small cell lung cancer)...Various compounds, e.g. 6a-e, especially compound 6e, were up to 5-fold more potent than suberanilohydroxamic acid (SAHA) in terms of cytotoxicity...These compounds also comparably inhibited HDACs with IC50 values in sub-micromolar range. Docking experiments showed that these compounds bound to HDAC2 at the enzyme active binding site with the same binding mode of SAHA, but with higher binding affinities.
    Journal
    |
    HDAC2 (Histone deacetylase 2)
    |
    Zolinza (vorinostat) • Beleodaq (belinostat) • REC-2282 • Duvyzat (givinostat) • nexturastat A