Sickle Cell Disease

Rituximab (anti-CD20) is an anti-CD20 chimeric monoclonal antibody used to treat certain autoimmune diseases and types of cancer.

GSK484 is a PAD4 inhibitor that effectively inhibits protein citrullination and the formation of neutrophil extracellular traps (NETs) by blocking the catalytic activity of PAD4. GSK484 suppresses the production of histone H3, MHC-I expression, CD8⁺ T cell activation, proliferation and inflammatory cytokine release. GSK484 reduces inflammation and bone destruction in collagen-induced rheumatoid arthritis, alleviates pain and mast cell activation in sickle cell disease, and improves myocardial ischemia-reperfusion injury and experimental colitis. In addition, GSK484 restores intestinal microbial homeostasis by reversing ferroptosis-induced dysbiosis. GSK484 can be used to study the disease mechanisms of rheumatoid arthritis, sickle cell disease, thrombosis, myocardial injury, colitis and other conditions.

ASP-8731 is an orally active BACH1 inhibitor. ASP-8731 activates antioxidant, anti-inflammatory and globin gene pathways by relieving the inhibitory effect of BACH1 on NRF2-mediated gene transcription. ASP-8731 significantly upregulates the expression of HMOX1, FTH1 and various globins (such as HGB, HBG, HBA), increases fetal hemoglobin (HbF) levels, and effectively induces F-cell production in hydroxyurea-unresponsive cells. Meanwhile, ASP-8731 reduces inflammatory responses and white blood cell counts by downregulating VCAM1, ICAM-1 and the phosphorylation level of NF-κB(p65), and blocks heme-induced glutathione depletion and microcirculatory stasis. ASP-8731 holds potential for inhibiting sickle cell disease and related hematological disorders.

Lithospermoside (Griffonin) is an orally active Na⁺/K⁺-ATPase inhibitor and hypoglycemic agent. Lithospermoside increases intracellular sodium levels in normal and sickle red blood cells. Lithospermoside reduces fasting blood glucose levels, improves glucose tolerance, and prevents weight loss in diabetic mice. Lithospermoside can be used in the research of sickle cell disease and diabetes.

SNOTRAP (S-nitrosylation trapping by triaryl phosphine) is a chemical probe for S-nitrosylated (SNO) proteins. SNOTRAP based proteomic pipeline can identify 1181 SNO proteins (1714 SNO sites) in the brain of mouse models. SNOTRAP can be used for nitrosative stress related diseases such as neurodegenerative disease, endotoxic shock, cancer, multiple sclerosis, and sickle cell disease.

DCN1 modulator-1 is a DCN1 modulator. DCN1 modulator-1 binds covalently to DCN2. DCN1 modulator-1 induces the expression of fetal hemoglobin mRNA (HBG1) and fetal hemoglobin protein (HbF). DCN1 modulator-1 is applicable to research related to sickle cell disease and thalassemia.

dWIZ-1 is an orally active molecular glue and chemical probe targeting the WIZ transcription factor, which based on an IMiD backbone, binding to human WIZ with an affinity of 3.5 μM. dWIZ-1 recruits WIZ to the cereblon-DDB1 complex via its ZF7 domain, thereby triggering proteasome-dependent degradation of WIZ. dWIZ-1 significantly induces fetal hemoglobin expression in erythroblasts while reducing the level of inhibitory H3K9 dimethylation at WIZ binding sites such as the β-globin locus. Meanwhile, dWIZ-1 does not affect the proliferation and differentiation of erythroblasts, and no cytotoxicity is observed in in vitro cells or cynomolgus monkey models. dWIZ-1 serves as a critical tool molecule for investigating the mechanism and underlying pathways of sickle cell disease.

(R)-FTY720-OMe is a selective SphK2 inhibitor with an IC₅₀ of 16.5  μM. (R)-FTY720-OMe can be used for cancer, fibrosis, and Alzheimer’s and sickle cell diseases research.

Lithospermoside (Griffonin) (Standard) is the analytical standard of Lithospermoside (HY-N0821). This product is intended for research and analytical applications. Lithospermoside is an orally active Na⁺/K⁺-ATPase inhibitor and hypoglycemic agent. Lithospermoside increases intracellular sodium levels in normal and sickle red blood cells. Lithospermoside reduces fasting blood glucose levels, improves glucose tolerance, and prevents weight loss in diabetic mice. Lithospermoside can be used in the research of sickle cell disease and diabetes.

Rivipansel is a small-molecule glycomimetic pan-selectin antagonist with inhibitory activity against E-selectin and P-selectin. Rivipansel binds tightly to the lectin domain of E-selectin, and selectively blocks the recognition of CD62L by E-selectin without affecting the binding of PSGL-1 to E-selectin. Rivipansel functionally inhibits the adhesion of hematopoietic cells to endothelial cells, and is applicable to research related to sickle cell disease.

INN-312 is a sickle hemoglobin (Hb S) inhibitor capable of penetrating red blood cell membranes. INN-312 inhibits sickling of sickle red blood cells under hypoxic conditions, increases the oxygen affinity of Hb, and moderately improves the solubility of deoxygenated Hb S. INN-312 can be used in research related to sickle cell disease.