P elongation occurs through the breaking of all hydrogen bonds involved in the β-turn.The hinge region of antithrombin in the Figure 5 complex could not be modelled due to its conformational flexibility, and amino acids P9-P14 are not seen in this structure. This conformational flexibility indicates an equilibrium may exist within the complex between a P14 P15 reactive site loop inserted antithrombin conformation and a P14 P15 reactive site loop expelled conformation. In support of this, analysis of the positioning of P15 Gly in the Figure 5 complex (labelled in model B) shows it to be inserted into beta sheet A (see model C). Effect of glycosylation on activity
α-Antithrombin and β-antithrombin differ in their affinity for heparin. The difference in dissociation constant between the two is threefold for the pentasaccharide shown in Figure 3 and greater than tenfold for full length heparin, with β-antithrombin having a higher affinity. The higher affinity of β-antithrombin is thought to be due to the increased rate at which subsequent conformational changes occur within the protein upon initial heparin binding. For α-antithrombin, the additional glycosylation at Asn-135 is not thought to interfere with initial heparin binding, but rather to inhibit any resulting conformational changes.Even though it is present at only 5–10% the levels of α-antithrombin, due to its increased heparin affinity, it is thought that β-antithrombin is more important than α-antithrombin in controlling thrombogenic events resulting from tissue injury. Indeed, thrombin inhibition after injury to the aorta has been attributed solely to β-antithrombin.
It is not indicated for the treatment of patients with primary central nervous system lymphoma.Approval was based on ZUMA-7, a randomized, open-label, multicenter trial in adults with primary refractory LBCL or relapse within twelve months following completion of first-line therapy. Participants had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous hematopoietic stem cell transplantation (HSCT). A total of 359 participants were randomized 1:1 to receive a single infusion of axicabtagene ciloleucel following fludarabine and cyclophosphamide lymphodepleting chemotherapy or to receive second-line standard therapy, consisting of two or three cycles of chemoimmunotherapy followed by high-dose therapy and autologous HSCT in participants who attained complete remission or partial remission. References
External links
"Axicabtagene ciloleucel". Drug Information Portal. U.S. National Library of Medicine. "Axicabtagene Ciloleucel". National Cancer Institute. 20 October 2017. "Axicabtagene Ciloleucel". NCI Drug Dictionary. National Cancer Institute.