2. Academic Validation
  3. Novel BTK inhibitor acalabrutinib (ACP-196) tightly binds to site I of the human serum albumin as observed by spectroscopic and computational studies

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.
Ali S Abdelhameed 1,  Amer M Alanazi 2,  Ahmed H Bakheit 3,  Eman S Hassan 4,  Rashed N Herqash 2,  Fahad M Almutairi 5
Affiliations

Affiliations

  • 1 King Saud University, Department of Pharmaceutical Chemistry, College of Pharmacy, P.O. Box 2457, Riyadh 11451, Saudi Arabia. Electronic address: [email protected].
  • 2 King Saud University, Department of Pharmaceutical Chemistry, College of Pharmacy, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
  • 3 King Saud University, Department of Pharmaceutical Chemistry, College of Pharmacy, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Department of Chemistry, Faculty of Science and Technology, El-Neelain University, P.O. Box 12702, Khartoum 11121, Sudan.
  • 4 Department of Medical Laboratory Sciences, Al-Ghad International Medical Sciences College, Female section, P.O. Box 4228, Riyadh 13315, Saudi Arabia.
  • 5 Biochemistry Department, Faculty of Science, University of Tabuk, P.O. Box 741, Tabuk 71491, Saudi Arabia.
PMID: 30664965 DOI: 10.1016/j.ijbiomac.2019.01.083
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 6.65-7.54 × 104 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.

Keywords

ACP-196; Acalabrutinib; Fluorescence spectroscopy; Human serum albumin.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-17600
    99.88%, BTK Inhibitor
    Btk