التفاصيل البيبلوغرافية
| العنوان: |
Synthesis of Carboxamides Tranylcypromine Analogues as LSD1 (KDM1A) Inhibitors for AML |
| المؤلفون: |
Teresa Borrello (8455695), Chak Hin Tam (8457083), Manar Shafat (6769637), Stuart Rushworth (8457100), Kristian Bowles (8467355), Sarah Bailey (5002244), Simon Crabb (8467356), Graham Packham (8467978), Patrick J. Duriez (8467996), Pr. Ganesan (8457118), Hanae Benelkebir (8473623), Leonard Douglas (8473626) |
| سنة النشر: |
2021 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biochemistry, Chemical Biology, KDM1A, LSD1, AML |
| الوصف: |
Lysine-specific demethylase 1 (LSD1/KDM1A) oxidatively removes methyl groups from histone proteins and its aberrant activity has been correlated with cancers including acute myeloid leukemia (AML). We report a novel series of tranylcypromine analogues with a carboxamide at the 4-position of the aryl ring. These compounds, such as 5a and 5b , had potent submicromolar IC 50 values for the inhibition of LSD1 as well as cell proliferation in a panel of AML cell lines. The dose-dependent increase in cellular expression levels of H3K4me2, CD86, CD11b and CD14 supported a mechanism involving LSD1 inhibition. The t -butyl and ethyl carbamate derivatives of these tranylcypromines, although inactive in LSD1 inhibition, were of similar potency in cell-based assays with a more rapid onset of action. This suggests carbamates can act as metabolically labile tranylcypromine prodrugs with superior pharmacokinetics. |
| نوع الوثيقة: |
report |
| اللغة: |
unknown |
| العلاقة: |
https://figshare.com/articles/preprint/Synthesis_of_Carboxamides_Tranylcypromine_Analogues_as_LSD1_KDM1A_Inhibitors_for_AML/11860824Test |
| DOI: |
10.26434/chemrxiv.11860824.v2 |
| الإتاحة: |
https://doi.org/10.26434/chemrxiv.11860824.v2Test |
| حقوق: |
CC BY-NC-ND 4.0 |
| رقم الانضمام: |
edsbas.523C091C |
| قاعدة البيانات: |
BASE |
