Novel BTK inhibitor acalabrutinib (ACP-196) tightly binds to site I of the human serum albumin as observed by spectroscopic and computational studies.
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Abdelhameed AS, Alanazi AM, Bakheit AH, Hassan ES, Herqash RN, Almutairi FM
Novel BTK inhibitor acalabrutinib (ACP-196) tightly binds to site I of the human serum albumin as observed by spectroscopic and computational studies.
Int J Biol Macromol. 2019 Apr 15;127:536-543. doi: 10.1016/j.ijbiomac.2019.01.083. Epub 2019 Jan 18.
- PubMed ID
- 30664965 [ View in PubMed]
- Abstract
Spectrofluorometric, UV-vis spectroscopic and theoretical tools were recruited to comprehend the interaction of acalabrutinib (ACP-196; ACLB) with human serum albumin (HSA). Fluorescence intensity determinations revealed that ACLB statically quenched the HSA-native fluorescence. Analysis of the observed fluorescence data resulting from the ACLB-HSA interaction presented binding constants in the range of 6.65-7.54x10(4)M(-1) with the studied temperatures. Those constants showed steady decline with the rising temperatures that further signifies static interaction of the HSA and ACLB. Binding energetics were also interpreted using the fluorescence-recorded results that exhibited a spontaneous exothermic binding reaction with a negative change in Gibbs free energy as well as negative enthalpy and positive entropy changes. Those results suggested the involvement of electrostatic forces as discovered by further computational investigation. Those docking results verified that ACLB binds to domain IIA (site I) of the HSA as demonstrated experimentally by site markers displacement binding studies. Circular dichroism studies along with the synchronous and 3D fluorescence observations showed that ACL binding does not alter the HSA conformation.
DrugBank Data that Cites this Article
- Drug Carriers
Drug Carrier Kind Organism Pharmacological Action Actions Acalabrutinib Serum albumin Protein Humans UnknownBinderDetails