Ask about this productRelated genes to: PKLR Blocking Peptide
- Gene:
- PKLR NIH gene
- Name:
- pyruvate kinase L/R
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 1q22
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-22
- Date modifiied:
- 2019-04-23
Related products to: PKLR Blocking Peptide
Related articles to: PKLR Blocking Peptide
- Pyruvate kinase deficiency (PKD) results from pathogenic variants in the PKLR gene and demonstrates marked clinical heterogeneity ranging from compensated hemolysis to severe transfusion-dependent anemia; however, novel variants continue to expand the genotypic spectrum of the disease. We report a case of a 10-month-old girl with transfusion-dependent chronic hemolytic anemia found to harbor a novel homozygous PKLR missense variant c.1376C>G (p.Ala459Gly). This variant has not previously been reported in the literature and was classified as a variant of uncertain significance (VUS) according to the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria. This report expands the mutational spectrum of PKD and highlights the importance of molecular testing in infants with unexplained chronic hemolytic anemia, especially in populations with high consanguinity rates. Although functional validation of the identified PKLR variant was not available, the patient's clinical and hematologic phenotype was highly consistent with severe PKD, supporting the variant as a candidate disease-associated alteration. - Source: PubMed
Publication date: 2026/07/29
Hassanien Sara SAlasmari Badriah GHanafy EhabMansour MohamedBabiker Ahlam - Diabetes mellitus affects hundreds of millions of people worldwide and remains a leading cause of multi-organ morbidity. Eriodictyol (Eri), a natural flavonoid enriched in edible plants and other citrus fruits, exhibits antioxidant, anti-inflammatory, and glucose-lowering properties in vitro. However, its systemic efficacy against diabetic hyperglycemia and tissue injury in vivo has not been systematically examined. - Source: PubMed
Publication date: 2026/08/25
Deng XuZheng JiaojiaoXiao Chunxia - Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy with a poor prognosis. However, the molecular mechanisms underlying CCA and its treatment options remain unclear and limited. - Source: PubMed
Gong BiyanXu XuejunXu TubingZhang DongYang LiLi CailingLi TingjunLuo Yuandeng - Post-treatment erythrocytosis (PT-E)-an increase in red blood cell counts after therapy-is an uncommon but reproducible finding in a subset of Hodgkin lymphoma (HL) survivors, and its biological basis remains undefined. - Source: PubMed
Publication date: 2026/08/05
Koyun DeryaYüksel SeherCivriz Bozdağ SinemTuncalı TimurKuzu IşınsuÖzcan Muhit - Pyruvate kinase (PKLR) is a key glycolytic enzyme that regulates red blood cell energy homeostasis. Although Mitapivat is the first approved allosteric activator for pyruvate kinase deficiency (PKD), its clinical utility is limited by metabolic and pharmacokinetic challenges, underscoring the need for improved analogues. This study aimed to identify novel Mitapivat-derived scaffolds with enhanced PKLR binding, stability, and drug-like properties using an integrated computational approach. A total of 190 structurally related derivatives were screened through molecular docking, pharmacophore modeling, frontier molecular orbital (HOMO-LUMO) analysis, 200 ns molecular dynamics (MD) simulations, MM/PBSA free energy calculations, ADMET profiling, and retrosynthetic feasibility assessment. Comparative analyses were performed against Mitapivat and phenylalanine, an endogenous PKLR inhibitor. Among the screened compounds, CHEMBL3729403 and CHEMBL3729860 emerged as the most promising candidates. CHEMBL3729403 exhibited the strongest docking affinity (-9.10 kcal/mol) and superior MD stability, with the lowest average RMSD (0.419 nm) and highest hydrogen-bond occupancy (1.039). MM/PBSA calculations revealed stronger binding free energies for CHEMBL3729403 (-26.39 ± 3.21 kcal/mol) and CHEMBL3729860 (-23.05 ± 3.59 kcal/mol) than Mitapivat (-21.35 ± 3.46 kcal/mol) and phenylalanine (-3.89 ± 3.91 kcal/mol). Pharmacophore analysis demonstrated conservation of the key interaction features required for PKLR activation, while HOMO-LUMO analysis revealed comparable electronic characteristics across the lead compounds, supporting their compatibility with ligand-protein interactions. ADMET profiling predicted favorable oral absorption (81.5% and 81.3%), good intestinal permeability, acceptable drug-likeness, and the absence of predicted mutagenic, tumorigenic, reproductive, or irritant liabilities for CHEMBL3729403 and CHEMBL3729860. Retrosynthetic analysis further supported their synthetic accessibility through feasible sulfonamide-coupling routes. Overall, CHEMBL3729403 and CHEMBL3729860 were identified as promising putative PKLR activators with improved predicted binding, stability, and pharmacokinetic properties compared with Mitapivat. These findings warrant further experimental validation to confirm their therapeutic potential in PKD and related metabolic disorders. - Source: PubMed
Publication date: 2026/08/12
Dermawan DoniAlotaiq Nasser