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Sickle cell anemia

Disease ID:862
Name:Sickle cell anemia
Associated with:2 targets
Database Links
Disease Ontology: DOID:10923


Role:  KCa3.1 is involved in erythrocyte dehydration during sickling
Drugs:  Clotrimazole, senicapoc
Therapeutic use:  Phase 3 clinical trials for ICA-17043 (senicapoc) were stopped in 2007 apparently due to lack of efficacy in reducing the incidence of sickling crisis
References:  1-3
selectin P (CD62)
Role:  The P-selectin/P-selectin glycoprotein ligand 1 (PSGL-1) interaction is involved in cell adhesion, largely between leukocytes, platelets and vascular endothelial cells. In Sickle cell disease P-selectin/PSGL-1 complexes promote abnormal adhesion of sickled erythrocytes to activated endothelial cells which precipitates vascular occlusion and pain crises.
Drugs:  Crizanlizumab
Comments:  Crizanlizumab binds to P-selectin and blocks interaction with PSGL-1, as a mechanism to reduce the frequency of vaso-occlusive crises in patients with sickle cell disease.
References:  4


No ligand related data available for Sickle cell anemia


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1. Ataga KI, Orringer EP, Styles L, Vichinsky EP, Swerdlow P, Davis GA, Desimone PA, Stocker JW. (2006) Dose-escalation study of ICA-17043 in patients with sickle cell disease. Pharmacotherapy, 26 (11): 1557-64. [PMID:17064199]

2. Brugnara C, de Franceschi L, Alper SL. (1993) Inhibition of Ca(2+)-dependent K+ transport and cell dehydration in sickle erythrocytes by clotrimazole and other imidazole derivatives. J Clin Invest, 92 (1): 520-6. [PMID:8326017]

3. Brugnara C, Gee B, Armsby CC, Kurth S, Sakamoto M, Rifai N, Alper SL, Platt OS. (1996) Therapy with oral clotrimazole induces inhibition of the Gardos channel and reduction of erythrocyte dehydration in patients with sickle cell disease. J Clin Invest, 97 (5): 1227-34. [PMID:8636434]

4. Kaur K, Kennedy K, Liles D. (2023) Crizanlizumab in sickle cell disease. Pain Manag, [Epub ahead of print]. DOI: 10.2217/pmt-2023-0031 [PMID:37850353]