REC-2282 / Recursion Pharma 
Welcome,         Profile    Billing    Logout  
 0 Diseases   1 Trial   1 Trial   70 News 
  • ||||||||||  CRA-026440 / Quest Diagnostics, KPT-9274 / Karyopharm, REC-2282 / Recursion Pharma
    Journal, Epigenetic controller:  Targeting DNA damage repair functions of two histone deacetylases, HDAC8 and SIRT6, sensitizes acute myeloid leukemia to NAMPT inhibition. (Pubmed Central) -  Mar 15, 2022   
    FFM was identified as a significant covariate on CL; however, it explained only a very small portion of the IIV; major factors contributing significantly to REC-2282 pharmacokinetic variability remain unidentified. 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.
  • ||||||||||  Ostarine (enobosarm) / Veru Inc, REC-2282 / Ohio State University, Recursion Pharma
    Journal:  Overcoming resistance to anabolic SARM therapy in experimental cancer cachexia with an HDAC inhibitor. (Pubmed Central) -  Jul 29, 2021   
    AR-42 mitigates catabolic gene activation and restores anabolic responsiveness to GTx-024. Combining GTx-024, a clinically established anabolic therapy, with AR-42, a clinically evaluated HDACi, represents a promising approach to improve anabolic response in cachectic patients.
  • ||||||||||  REC-2282 / Recursion Pharma
    Trial completion, Enrollment change:  HDAC Inhibitor AR-42 and Pomalidomide in Treating Patients With Relapsed Multiple Myeloma (clinicaltrials.gov) -  Jun 15, 2021   
    P1b,  N=9, Completed, 
    Combining GTx-024, a clinically established anabolic therapy, with AR-42, a clinically evaluated HDACi, represents a promising approach to improve anabolic response in cachectic patients. Suspended --> Completed | N=72 --> 9
  • ||||||||||  REC-2282 / Ohio State University, Recursion Pharma
    P1 data, Journal:  Phase I study of AR-42 and decitabine in acute myeloid leukemia. (Pubmed Central) -  Apr 29, 2021   
    Two patients achieved a CRi and one patient achieved a CR for an ORR of 23.1%. The higher risk features of this patient population and the dosing schedule of AR-42 may have led to the observed clinical response and failure to meet the biologic endpoint.
  • ||||||||||  REC-2282 / Ohio State University, Recursion Pharma
    [VIRTUAL] Achiral derivatives of hydroxamate AR-42 potently inhibit HDAC1 and cancer cell proliferation (On Demand Poster) -  Aug 20, 2020 - Abstract #ACSFall2020ACS-Fall_5514;    
    Molecular modelling and structure-activity relationships support binding to HDAC1 with the hydroxamate chelating to Zn2+, the adjacent aromatic ring interacting with Phe150 and Phe205, the benzamide NH forming a hydrogen bond with Asp99, and the tetrahydropyran acting as a hydrophobic shield from water at the exposed surface of the enzyme. Such potent HDAC1 inhibitors may show benefit in a range of disease indications (cancers, parasitic infections, inflammatory conditions) where AR-42 is active.
  • ||||||||||  REC-2282 / Recursion Pharma
    Trial completion date, Trial primary completion date:  HDAC Inhibitor AR-42 and Pomalidomide in Treating Patients With Relapsed Multiple Myeloma (clinicaltrials.gov) -  Apr 9, 2020   
    P1b,  N=72, Suspended, 
    Trial completion date: Oct 2022 --> Oct 2023 | Trial primary completion date: Oct 2020 --> Oct 2021 Trial completion date: Dec 2019 --> Dec 2020 | Trial primary completion date: Dec 2019 --> Dec 2020
  • ||||||||||  REC-2282 / Recursion Pharmaceuticals, Ohio State University
    Journal:  Design, Synthesis and Evaluation of Novel 3/4-((Substituted benzamidophenoxy)methyl)-N-hydroxybenzamides / propenamides as Histone Deacetylase Inhibitors and Antitumor Agents. (Pubmed Central) -  Mar 2, 2020   
    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.
  • ||||||||||  AR 42 / Arno Therap
    Achiral AR-42 analogues as HDAC1 inhibitors with antiproliferative activity and selectivity (Exhibit Hall D, Pennsylvania Convention Center) -  Feb 13, 2020 - Abstract #ACSSp2020ACS_Sp_4081;    
    Molecular modelling and structure-activity relationships are consistent with the hydroxamate chelating to Zn2+ in HDAC1, an adjacent aromatic ring forming interacting with Phe150 and Phe205, a benzamide NH hydrogen bonding to Asp99, and a cycloalkyl group providing a hydrophobic shield for the solvent exposed surface of the enzyme. These compounds appear to be promising for evaluation in a range of cancers, parasitic infections, and inflammatory conditions.
  • ||||||||||  AR 42 / Arno Therap
    Journal:  Effect of Docosahexaenoic Acid on Ca Signaling Pathways in Cerulein-Treated Pancreatic Acinar Cells, Determined by RNA-Sequencing Analysis. (Pubmed Central) -  Jan 10, 2020   
    In the present study, we determined the effect of DHA on key regulators of Ca signaling in cerulein-treated pancreatic acinar AR42 J cells...The results of real-time PCR confirmed that DHA inhibits cerulein-induced IP3R1 and RyR2 gene expression, and demonstrated that DHA pre-treatment decreases the expression of the Relb gene, which encodes a component of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcriptional activator complex, and the c-fos gene, which encodes a component of activator protein-1 (AP-1) transcriptional activator complex. Taken together, DHA inhibits mRNA expression of IP3R1, RyR2, Relb, and c-fos, which is related to Ca network in cerulein-stimulated PACs.
  • ||||||||||  AR 42 / Arno Therap
    Journal:  Anti-oral Squamous Cell Carcinoma Effects of a Potent TAZ Inhibitor AR-42. (Pubmed Central) -  Jan 5, 2020   
    Additionally, the inhibitory effect of AR-42 against TAZ, as well as its anti-OSCC activity could be also observed in SCC9 xenograft model. Taken together, AR-42 deserves to be further studied as a TAZ inhibitor, and is worthy to be further assessed as a potential drug candidate for OSCC treatment.
  • ||||||||||  REC-2282 / Recursion Pharma
    Trial completion date, Trial primary completion date:  HDAC Inhibitor AR-42 and Pomalidomide in Treating Patients With Relapsed Multiple Myeloma (clinicaltrials.gov) -  Nov 15, 2019   
    P1b,  N=72, Suspended, 
    Taken together, AR-42 deserves to be further studied as a TAZ inhibitor, and is worthy to be further assessed as a potential drug candidate for OSCC treatment. Trial completion date: Mar 2019 --> Dec 2019 | Trial primary completion date: Mar 2019 --> Dec 2019
  • ||||||||||  AR 42 / Arno Therap, Zejula (niraparib) / GSK, J&J, Takeda
    Journal, PARP Biomarker:  Valproate augments Niraparib killing of tumor cells. (Pubmed Central) -  Sep 14, 2019   
    Tumors previously exposed to niraparib had activated the ERK1/2 and AKT-mTOR pathways that correlated with increased plasma levels of IL-8, MIF, EGF, uPA and IL-12. Collectively our findings argue that the addition of HDAC inhibitors to niraparib enhances the anti-cancer activity of the PARP1 inhibitor niraparib.
  • ||||||||||  AR 42 / Arno Therap
    Journal:  Determination of the color removal efficiency of laccase enzyme depending on dye class and chromophore. (Pubmed Central) -  Sep 13, 2019   
    As a result, it can be said that the highest decolorization rate was achieved for the reactive dye having formazan copper complex (RB220) chromophore. On the other hand, the enzymatic degradation of basic dye (BB9) was found to be rather difficult compared to the acid and reactive dyes used in this study and the maximum color removal was 42.8% after seven days.
  • ||||||||||  REC-2282 / Recursion Pharma
    Trial completion date, Trial primary completion date, Epigenetic controller:  Exploratory Evaluation of AR-42 Histone Deacetylase Inhibitor in the Treatment of Vestibular Schwannoma and Meningioma (clinicaltrials.gov) -  Nov 20, 2018   
    P1,  N=5, Active, not recruiting, 
    Collectively, our data reinforce the concept that the irreversible ERBB1/2/4 inhibitor neratinib has the potential for use in the treatment of tumors expressing mutant RAS proteins. Trial completion date: Oct 2018 --> Oct 2022 | Trial primary completion date: Oct 2018 --> Oct 2020
  • ||||||||||  REC-2282 / Recursion Pharma
    Clinical:  HDAC Inhibitor AR-42 and Pomalidomide in Treating Patients With Relapsed Multiple Myeloma (clinicaltrials.gov) -  Jul 6, 2017   
    P1b,  N=72, Suspended, 
    Tumor cells that had adapted through therapy exhibited elevated HGF expression and the c-MET inhibitor crizotinib enhanced AR42 pazopanib lethality in this evolved drug-resistant population. Recruiting --> Suspended