Exploring the possibility of drug repurposing for cancer therapy targeting human lactate dehydrogenase A: a computational approach

Exploring Darunavir, Rilpivirine and Etravirine as Potential Therapies for Bladder Cancer: Efficacy and Synergistic Effects

“…More recently, an in silico study has demonstrated that DRV has a high affinity for binding to the active site of the human lactate dehydrogenase A (LDHA) enzyme, with high stability hydrogen bonds. This is similar to known inhibitors and the article concludes that DRV can be a potential LDHA inhibitor [ 32 ]. This enzyme converts pyruvate into lactate and is often upregulated in cancer, promoting several of the known hallmarks of cancer, such as increased proliferation, cell invasion and metastasis, angiogenesis, and immune escape, and its inhibition has been known to impair cancer progression [ 48 ].…”

“…In this study, DRV, RPV, and ETV, three antiretroviral drugs, were studied in UM-UC-5 bladder cancer cells. These drugs have been selected because they have been shown to have effects on cancer in studies found in the literature, namely ETV in ovarian cancer metastasis [ 30 ], RPV in pancreatic cancer [ 31 ], and DRV has demonstrated in silico evidence of inhibiting enzymes overexpressed in several cancer types [ 32 ]. Overall, the best drug tested in this study was ETV, in a concentration and time-dependent manner, having a relatively low IC 50 at 24 and 48 h (24.76 µM and 32.77 µM), but with the overall lowest IC 50 being at 72 h (5.923 µM).…”

Genetically predicted 486 blood metabolites in relation to risk of colorectal cancer: A Mendelian randomization study

“…For the six known metabolites that have been identified in this study that are associated with CRC risk, we searched for relevant targets of metabolites in previously published studies. We found that lactate dehydrogenase A (LDHA) regulated pyruvate metabolism and was significantly associated with the development of cancer, 44 , 45 while the eQTL and pQTL of LDHA in blood were also available in publicly available databases. Few targets with important regulatory effects on other metabolites have been reported.…”

Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFR WT , EGFR T790M , and EGFR L858R )

“…A molecular docking study was achieved to establish a deep insight into the binding mode of the R - and S -enantiomers for the most potent antitumor compounds, 10c and 10d , within the ATP-binding pocket of the crystal structures for each enzyme: EGFR WT (PDB code: 1M17) 91 , EGFR T790M (PDB code: 2JIV) 92 and EGFR L858R (PDB code: 4LQM) by using “molecular operating environment (MOE) version 2019.0102” 93 . Visualisation of interactions between ligands and binding sites was accomplished via discovery studio visualiser (BIOVIA-2021.DS2021Client) 94 , 95 . The active site of the EGFR enzyme contains essential amino acids; Lys721, Met742, Met766, Gly767, Met769, Leu694, and Asp831 which are chiefly targeted by EGFR inhibitors 96 .…”