ERCC1 inhibitors(ERCC excision repair 1, endonuclease non-catalytic subunit inhibitors)、ERCC4 inhibitors(ERCC excision repair 4, endonuclease catalytic subunit inhibitors)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

University of Alberta

在研机构

University of Alberta

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C29H34ClN5O2

InChIKeySMEFQJGKKXYNAS-UHFFFAOYSA-N

CAS号2376044-25-4

关联

100 项与 ERCC1-XPFinhibitors(University of Alberta) 相关的临床结果

登录后查看更多信息

100 项与 ERCC1-XPFinhibitors(University of Alberta) 相关的转化医学

登录后查看更多信息

100 项与 ERCC1-XPFinhibitors(University of Alberta) 相关的专利（医药）

登录后查看更多信息

项与 ERCC1-XPFinhibitors(University of Alberta) 相关的文献（医药）

2024-06-13·ACS Medicinal Chemistry Letters

Synthesis and Antifungal Activity of Stereoisomers of Mefloquine Analogs

Article

作者: Meyers, Marvin J ; Alden, Kathryn M ; Guin, Soumitra ; Krysan, Damian J

Cryptococcal neoformans and Candida albicans are among the most prevalent causes of life-threatening fungal infections globally. The high mortality associated with these infections despite current antifungal therapy highlights the need for new drugs. In our previous work, we demonstrated that an analogue of the clinically used antimalarial mefloquine, (8-chloro-2-(4-chlorophenyl)quinolin-4-yl)(piperidin-2-yl)methanol (4377), has both antifungal activity and the ability to penetrate the central nervous system. Herein we describe the synthesis and antifungal assay of all four stereoisomers of 4377. All four stereoisomers retain potent antifungal activity with the erythro enantiomers having MIC values of 1 and 4 μg/mL against C. neoformans and C. albicans, respectively, and threo enantiomers, MIC values of 2 and 8 μg/mL, respectively. These results indicate that the stereochemistry of the piperidine methanol group is not critical for the antifungal properties of 4377 and gives guidance to future medicinal chemistry optimization efforts.

2021-03-01·Behavioural Brain Research3区 · 心理学

Potential antidepressant-like effect of piperazine derivative LQFM212 in mice: Role of monoaminergic pathway and brain-derived neurotrophic factor

3区 · 心理学

Article

作者: Siqueira, Lorrayne ; Florentino, Iziara Ferreira ; Cardoso, Carina Sofia ; Ghedini, Paulo César ; Menegatti, Ricardo ; da Silva, Daiany Priscilla Bueno ; de Brito, Adriane Ferreira ; da Silva, Dayane Moreira ; Costa, Elson Alves ; de Carvalho, Pablinny Moreira Galdino ; Moreira, Lorrane Kelle da Silva

Major depression disorder (MDD) is one of the most widespread and debilitating psychiatric diseases and may be associated with other mental disorders such as anxiety. Despite advances in neurobiology studies, currently no established mechanism can explain all facets of MDD, and available drugs often show therapeutic delay for clinical effectiveness and response rates in patients are around 50 %. Previous activities of piperazine derivatives on CNS are indicators of its therapeutic potential for treating mental disorders. In this regard, we have previously shown that the piperazine derivative 2,6-di-tert-butyl-4-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)phenol (LQFM212) has anxiolytic-like activity which involves serotonergic pathway, nicotinic receptors and BZD-site of GABA_A receptor, without cognitive impairments. Herein, was evaluated the potential antidepressant-like effect of LQFM212 on forced swimming test (FST) after a single dose of 54 μmol/kg and after repeated treatment for 15 days in mice. Pretreatment with WAY-100635, PCPA, prazosin, SCH-23390, sulpiride or AMPT reversed the antidepressant-like effect on FST, suggesting that monoaminergic pathway contributes for effects of LQFM212. Furthermore, repeated treatment with LQFM212 increased hippocampal BDNF levels dosed by ELISA kit. In assessment of possible adverse effects, repeated treatment with LQFM212 did not alter the body weight of the animals, glutathione levels in the liver, and serum levels of AST, ALT, urea, and creatinine. Taken together, the results showed that LQFM212 has an antidepressant-like effect that involves monoaminergic pathway and increased BDNF levels. This compound represents promising candidate for prototype of psychoactive drugs for treatment of anxiety and depression disorders since these pathological conditions may exist in comorbidities.

Turkish Journal of Biology

A Novel Algorithm for the Virtual Screening of Extensive Small Molecule Libraries Against ERCC1/XPF Protein-Protein Interaction for the Identification of Therapeutic Resistance-Bypassing Small Anticancer Molecules

Article

作者: Ghazy, Salma ; Oktay, Lalehan ; Durdaği, Serdar

Background and aim:Cancer cell’s innate chemotherapeutic resistance continues to be an obstacle in molecular oncology. This theory is firmly tied to the cancer cells’ integral DNA repair mechanisms continuously neutralizing the effects of chemotherapy. Amidst these mechanisms, the nuclear excision repair pathway is crucial in renovating DNA lesions prompted by agents like Cisplatin. The ERCC1/XPF complex stands center-stage as a structure specific endonuclease in this repair pathway. Targeting the ERCC1/XPF dimerization brings forth a strategy to augment chemotherapy by eschewing the resistance mechanism integral to cancer cells. This study tracks and identifies small anticancer molecules, with ERCC1/XPF inhibiting potential, within extensive small-molecule compound libraries.Materials and Methods:A novel hybrid virtual screening algorithm, conjoining ligand- and target-based approaches, was developed. All-atom molecular dynamics (MD) simulations were then run on the obtained hit molecules to reveal their structural and dynamic contributions within the binding site. MD simulations were followed by MM/GBSA calculations to qualify the change in binding free energies of the protein/ligand complexes throughout MD simulations.Results:Conducted analyses highlight new potential inhibitors AN-487/40936989 from the SPECS SC library, K219-1359 and K786-1161 from the ChemDiv Representative Set library as showing better activity than previously discovered ERCC1/XPF inhibitor, CHEMBL3617209.Conclusion:The algorithm implemented in this study expands our comprehension of chemotherapeutic resistance and how to overcome it through identifying ERCC1/XPF inhibitors with the aim of enhancing chemotherapeutic impact giving hope for ameliorated cancer treatment outcomes.

100 项与 ERCC1-XPFinhibitors(University of Alberta) 相关的药物交易

登录后查看更多信息