DCLRE1A

Last update 08 May 2025

Basic Info

Synonyms

Beta-lactamase DCLRE1A, DCLRE1A, DNA cross-link repair 1A

+ [8]

Introduction

May be required for DNA interstrand cross-link repair. Also required for checkpoint mediated cell cycle arrest in early prophase in response to mitotic spindle poisons. Possesses beta-lactamase activity, catalyzing the hydrolysis of penicillin G and nitrocefin (PubMed:31434986). Exhibits no activity towards other beta-lactam antibiotic classes including cephalosporins (cefotaxime) and carbapenems (imipenem) (PubMed:31434986).

100 Clinical Results associated with DCLRE1A

100 Translational Medicine associated with DCLRE1A

0 Patents (Medical) associated with DCLRE1A

162

Literatures (Medical) associated with DCLRE1A

01 Mar 2025·Heart & Lung

Pulmonary arterial stiffness and vascular tone in pulmonary hypertension: Insights from waveform-derived reflection index and hemodynamic correlations

Article

Author: Oğuz, Mustafa ; Yılmaz, İrem ; Uzun, Mehmet ; Duran, Nilüfer Ekşi ; Erdem, Almina ; Demirci, Murat

BACKGROUNDPulmonary hypertension (PH) involves increased arterial stiffness and reduced vascular tone, affecting pulmonary arterial wave reflections. The Reflection Index (RI) may provide insights into these changes.OBJECTIVEThis study examines the utility of RI in PH patients by correlating it with key right heart catheterization (RHC) parameters.METHODSPatients who underwent RHC with a preliminary diagnosis of PH, including those with normal RHC findings and those diagnosed with Group 1 and Group 4 PH, were included in the study. RI was defined as the ratio of systolic to diastolic pressure differences from pulmonary arterial waveforms and compared with hemodynamic, clinical, and echocardiographic parameters.RESULTSThe study included 115 patients (mean age 53.92 ± 16.43 years; 43.5% male). RI showed significant correlations with key RHC parameters, such as sPAP (r=0.359, p<0.001), dPAP (r=0.322, p<0.001), mPAP (r=0.339, p<0.001), PVR (r=0.431, p<0.001), and pSO2 (r=-0.243, p=0.011). Among echocardiographic measures, RI correlated with TRV (r=0.377, p<0.001) and echo sPAP (r=0.359, p<0.001). In multivariable analysis, RI (OR:1.032, p=0.003) and NT-proBNP (OR:1.004, p=0.049) remained significant predictors of PH. ROC analysis demonstrated the moderate predictive power for RI (AUC=0.806, p<0.001), with 76.4% sensitivity and 78.5% specificity at a cut-off of 232.05.CONCLUSIONRI is a valuable parameter for assessing pulmonary arterial stiffness and vascular tone in patients with PAH and CTEPH. Significant correlations were observed with key hemodynamic parameters, including PVR and mPAP. Additionally, RI demonstrated moderate predictive power for PH. These findings highlight the potential of RI as an independent marker of vascular health, providing direct insights into the pulmonary arterial bed.

01 Mar 2025·Bioorganic Chemistry

Function and inhibition of the DNA repair enzyme SNM1A

Review

Author: Berney, Mark ; McGouran, Joanna F ; Ferguson, Steven

SNM1A is an enzyme involved in several important biological pathways. To date, most investigations have focused on its role in repairing interstrand crosslinks, a highly cytotoxic form of DNA damage. SNM1A acts as a 5'-3' exonuclease, displaying an unusual capability to digest DNA past the site of a crosslink lesion. Recently, additional functions of this enzyme in the repair of DNA double-strand breaks and critically shortened telomeres have been uncovered. Furthermore, SNM1A is involved in two cell cycle checkpoints that arrest cell division in response to DNA damage. Inhibition of both DNA repair enzymes and cell cycle checkpoint proteins are effective strategies for cancer treatment, and SNM1A is therefore of significant interest as a potential therapeutic target. As a member of the metallo-β-lactamase superfamily, SNM1A is postulated to contain two metal ions in the active site that catalyse hydrolysis of the phosphodiester backbone of DNA. Substrate-mimic probes based on a nucleoside or oligonucleotide scaffold appended with a metal-binding group have proven effective in vitro. High-throughput screening campaigns have identified potent inhibitors, some of which were successful in sensitising cells to DNA-damaging cancer drugs. This review discusses the biological role, structure, and mechanism of action of SNM1A, and the development of SNM1A inhibitors for cancer therapy.

01 Feb 2025·Dermatology and Therapy

Deucravacitinib: Adverse Events of Interest Across Phase 3 Plaque Psoriasis Trials

Article

Author: Ferris, Laura K ; Scharnitz, Thomas ; Sobell, Jeffrey M ; Merola, Joseph F ; Sofen, Howard ; Scotto, Julie ; Daamen, Carolin ; Osborne, John ; Vaile, John ; Lebwohl, Mark ; Jou, Ying-Ming

INTRODUCTIONDeucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in multiple countries for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. The safety and efficacy of deucravacitinib in psoriasis has been demonstrated through 3 years in the phase 3 POETYK PSO-1, PSO-2, and long-term extension (LTE) trials enrolling adults with moderate to severe plaque psoriasis.METHODSTo review the effect of deucravacitinib treatment on adverse events of interest (AEIs) over 3 years in POETYK PSO-1, PSO-2, and LTE, cumulative exposure-adjusted incidence rates (EAIRs) of AEIs were recorded through 3 years.RESULTSAEIs and 3-year EAIRs of select infections included serious infections (2.5/100 person-years [PY]), COVID-19 (1.6/100 PY), and herpes zoster (0.6/100 PY). Excluding COVID-19, the serious infections EAIR was 0.9/100 PY. Major adverse cardiovascular event (MACE) and venous thromboembolism EAIRs were 0.3/100 PY and 0.1/100 PY, respectively. The EAIRs for malignancies were 0.9/100 PY overall and 0.5/100 PY, excluding nonmelanoma skin cancer (NMSC). Cutaneous events included acne (EAIR, 1.3/100 PY) and folliculitis (EAIR, 1.1/100 PY). Three-year cumulative EAIRs generally remained stable or decreased relative to 1-year rates. EAIRs of non-COVID-19 serious infections, malignancies excluding NMSC, and MACE through 3 years were consistent with rates for other antipsoriatic agents from clinical trials, disease registries, and real-world claims data.CONCLUSIONIn adults with plaque psoriasis treated with deucravacitinib, the cumulative incidence of AEIs remained comparable or decreased over 3 years of follow-up and aligned with comparison data for other antipsoriatic therapies.

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DCLRE1A

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