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 (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 - To share the experience of diagnosis and treatment on hereditary spherocytosis (HS) with idiopathic pulmonary hemosiderosis (IPH). - Source: PubMed
Publication date: 2026/07/22
Li Wen XiangYang JingDong TingWu Deng YanMa Li NaWu Hui Min - Leprosy remains a major public health challenge in the state of Amazonas, Brazil, despite a remarkable 95.7% reduction in detection rates between 1981 and 2024. In 2024, 326 cases were reported, 80.4% of which were new diagnoses, predominantly multibacillary forms, with 9.3% presenting grade 2 disability on diagnosis. The continued occurrence of cases among children under 15 years of age (3.4%) indicates active transmission, particularly in geographically isolated municipalities. The Fundação Hospitalar Alfredo da Matta (FUHAM) serves as the main regional reference center, coordinating surveillance, diagnosis, rehabilitation and research activities. The decentralization of primary care and the integration of telehealth strategies have strengthened diagnostic capacity and improved the management of leprosy reactions. Historically, Amazonas has played a pivotal role in advancing scientific knowledge on leprosy, from early reports of dapsone resistance to participation in key clinical trials such as U-MDT/CT-BR, and studies on leprosy/HIV coinfection, immunopathogenesis and host genetic susceptibility (NOD2, IFNG, PKLR). More recently, genomic surveillance in the region has identified both classical and novel antimicrobial resistance mutations, consolidating Amazonas as a sentinel site for molecular monitoring. Persistent challenges include limited professional training, delayed diagnosis and ongoing social stigma. Research priorities for the next decade include strengthening active case detection, validating simplified diagnostic algorithms, expanding antimicrobial resistance monitoring, exploring genetic determinants of susceptibility and adopting One Health approaches to understand environmental and zoonotic transmission. These integrated strategies are crucial to sustain progress toward the elimination of leprosy as a public health problem in the Amazonian context. - Source: PubMed
Publication date: 2026/07/24
Santos MônicaFerreira MathiasFarias ClaudiaBindá AdrianaPedrosa Valderiza LourençoTalhari Carolina - Pyruvate kinase liver and red blood cells (PKLR) is linked to metabolic dysfunction-associated steatotic liver disease (MASLD). Previous study, we identified JNK-IN-5A, a c-Jun N-terminal kinase (JNK) inhibitor that suppresses PKL expression in HepG2 cells using computational drug repurposing and screened out four hit JNK-IN-5A derivatives (SET-151, SET-152, SET-162, SET-130). - Source: PubMed
Publication date: 2026/07/01
Kim WoongheeLi MengzhenLiao XinmengÖzmen SevilayYıldız EdanurSaraçoğlu MelikBaba CemCelikezen Fatih CaglarAtalay Said AliAkkuş Ahmet TuğrulAlper FatihJin HanYang HongIqbal ShaziaSebhaoui JihadAshraf SajdaBelmen BurcuBoren JanUhlen MathiasZhang ChengTurkez HasanMardinoglu Adil - To investigate the clinical features, treatment, and prognosis of pyruvate kinase deficiency (PKD) caused by gene variants. - Source: PubMed
Wang WenZhao Yan-XiaWang Ling-ZhenJiang FanYang JingSun Li-RongXu Hui-Juan