SGK1 inhibition induces fetal hemoglobin expression and delays polymerization in sickle erythroid cells

Article Chemistry, Medicinal

Rational Design of Highly Potent, Selective, and Bioavailable SGK1 Protein Kinase Inhibitors for the Treatment of Osteoarthritis

Nis Halland et al.

Summary: A highly selective SGK1 inhibitor with optimized safety and pharmacokinetic profile for oral dosing has been identified as a potential disease-modifying agent for osteoarthritis.

JOURNAL OF MEDICINAL CHEMISTRY (2022)

Add to Collection

Letter Hematology

Early initiation of disease-modifying therapy can impede or prevent diffuse myocardial fibrosis in sickle cell anemia

Omar Niss et al.

BLOOD (2022)

Add to Collection

Article Hematology

Fetal hemoglobin rescues ineffective erythropoiesis in sickle cell disease

Sara El Hoss et al.

Summary: This study confirms the presence of ineffective erythropoiesis in sickle cell disease and highlights an anti-apoptotic role for HbF during the terminal stages of erythroid differentiation. The findings suggest that the beneficial effect of increased HbF levels on anemia is not only due to the extended lifespan of red blood cells, but also a result of decreased ineffective erythropoiesis.

HAEMATOLOGICA (2021)

Add to Collection

Review Oncology

SGK1 in Human Cancer: Emerging Roles and Mechanisms

Yiwen Sang et al.

Summary: SGK1, a member of the AGC subfamily of protein kinases, plays a significant role in tumorigenesis and cancer progression, serving as a potential diagnostic and prognostic biomarker for various types of cancer.

FRONTIERS IN ONCOLOGY (2021)

Add to Collection

Article Medicine, Research & Experimental

SGK1 inhibition in glia ameliorates pathologies and symptoms in Parkinson disease animal models

Oh-Chan Kwon et al.

Summary: Inhibiting SGK1 in glial cells corrects their pro-inflammatory properties, enhances their ability to scavenge glutamate toxicity, and prevents glial cell senescence and mitochondrial damage, showing potential therapeutic value for treating neurodegenerative disorders like PD and AD.

EMBO MOLECULAR MEDICINE (2021)

Add to Collection

Article Hematology

MetAP2 inhibition modifies hemoglobin S to delay polymerization and improves blood flow in sickle cell disease

Melanie Demers et al.

Summary: This study investigated a novel approach to modify HbS and decrease polymerization by inhibiting MetAP2, which cleaves the initiator methionine from Val1 of alpha-globin and beta(S)-globin. The results showed that MetAP2 inhibition increases oxygen affinity of HbS and delays polymerization under hypoxia. Further research on MetAP2 inhibition as a potential therapeutic target for SCD is warranted.

BLOOD ADVANCES (2021)

Add to Collection

Article Hematology

Treatment of sickle cell disease by increasing oxygen affinity of hemoglobin

Eric R. Henry et al.

Summary: Voxelotor is a drug used to treat sickle cell disease by reducing sickling through increasing the concentration of nonpolymerizing, high oxygen affinity hemoglobin. Studies show that while Voxelotor can reduce sickling and decrease hemolysis, it only increases overall oxygen delivery at very low oxygen pressures.

BLOOD (2021)

Add to Collection

Article Hematology

Early initiation of hydroxyurea (hydroxycarbamide) using individualised, pharmacokinetics-guided dosing can produce sustained and nearly pancellular expression of fetal haemoglobin in children with sickle cell anaemia

Charles T. Quinn et al.

Summary: Hydroxyurea is an effective treatment for sickle cell anaemia, with individualized, pharmacokinetics-guided dosing achieving sustained near-pancellular or pancellular HbF expression, which should be considered an achievable goal for children with SCA treated with hydroxyurea at optimal doses.

BRITISH JOURNAL OF HAEMATOLOGY (2021)

Add to Collection

Review Hematology