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

Alanazi, Amer M.; Bakheit, Ahmed H.; Hassan, Eman S.; Herqash, Rashed N.; Almutairi, Fahad M.

doi:10.1016/j.ijbiomac.2019.01.083

Cited by 20 publications

(11 citation statements)

References 43 publications

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“…This indicated that 9-OHPhe did not perturb the microenvironment around Trp and Tyr residues. 41 Moreover, the K sv values for Tyr and Trp residues in the HSA-9-OHPhe system were calculated to be 4.28 × 10 4 and 1.29 × 10 5 L·mol –1 , respectively, which suggested that Trp residues played a more important role in the interaction of HSA with 9-OHPhe than Tyr.…”

Section: Resultsmentioning

confidence: 98%

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Probing the Interaction between Human Serum Albumin and 9-Hydroxyphenanthrene: A Spectroscopic and Molecular Docking Study

et al. 2020

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9-Hydroxyphenanthrene (9-OHPhe), the representative hydroxyl metabolite of phenanthrene, has generated increasing concern as it is potentially hazardous to organisms. Herein, multispectroscopic and molecular docking techniques were applied to investigate the molecular interaction of human serum albumin (HSA) with 9-hydroxyphenanthrene (9-OHPhe) under simulated physiological conditions. Steady-state fluorescence and time-resolved fluorescence spectral analysis showed that 9-OHPhe quenched HSA fluorescence through a mixed static and dynamic process. HSA can bind with 9-OHPhe to form a 1:1 complex, with binding constants of 1.28 × 10 5 , 1.36 × 10 5 , and 1.26 × 10 5 L·mol –1 at 298.15, 303.15, and 308.15 K, respectively. The strong binding between HSA and 9-OHPhe is spontaneous and entropy-driven. Molecular docking indicated that the optimal binding site of 9-OHPhe with HSA was located in the IA subdomain of HSA. Thermodynamic analysis and molecular docking results suggested that hydrophobic interactions and hydrogen bond force dominated the binding process of HSA with 9-OHPhe. Specifically, 9-OHPhe formed hydrophobic interactions with LEU134, LEU139, ILE142, LEU154, PHE157, ALA158, and TYR161 and formed a 1.86 Å hydrogen bond with LEU135. Circular dichroism spectral analysis showed that the α-helical content of HSA decreased from 52.3 to 50.9% after adding 9-OHPhe with a ratio of 1:1. The obtained results are hoped to provide basic data for understanding the potential effects of the hydroxyl metabolites of PAHs on functional biomacromolecules.

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Section: Resultsmentioning

confidence: 98%

“… 40 When setting Δλ at 15 and 60 nm, the synchronous fluorescence spectra of HSA represent the characteristic information of Tyr and Trp residues, respectively. 41 The synchronous fluorescence spectra of HSA with various concentrations of 9-OHPhe were measured and are shown in Figure 5 .…”

Section: Resultsmentioning

confidence: 99%

Probing the Interaction between Human Serum Albumin and 9-Hydroxyphenanthrene: A Spectroscopic and Molecular Docking Study

et al. 2020

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“…UV‐Vis absorption spectroscopy was used to study the interaction between protein and ligand 49 . According to Figure.…”

Section: Resultsmentioning

confidence: 99%

Binding mechanism of lipase with Lentinus edodes mycelia polysaccharide by multi‐spectroscopic methods

Liu

Chen

et al. 2021

J of Molecular Recognition

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It is an effective strategy to avoid obesity by inhibiting the activity of lipase. In this study, the binding mechanism of lipase and Lentinus edodes mycelia polysaccharide (LMP) were explored with multi‐spectral methods, for example, three‐dimensional (3D) fluorescence, Fourier‐transformed infrared (FT‐IR), and Raman spectra. At 290 K, the binding constant was 2.44 × 105 L/mol, there was only one binding site between LMP and lipase. Static quenching was the quenching mechanism. The major forces were hydrogen bonding and van der Waals force. The binding of LMP to lipase impacted the microenvironment around tyrosine and tryptophan residues. The polarity around these residues was decreased and hydrophobicity was enhanced. This study not only revealed the binding mechanism of LMP on lipase but also provided scientific evidence for expanding the application of LMP in functional food industries.

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“…15 Such external signals from the leukemia microenvironment can supplement intrinsic oncogenic lesions, thereby promoting maintenance and expansion of the Chronic lymphocytic leukemia (CLL) clone. 14,[16][17] In reported Spectrofluorometric method, 18 observed fluorescence data resulting from the acalabrutinib (ACLB) -human serum albumin (HSA) interaction presented binding constants in the range of 6.65-7.54×10 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.…”

Section: Introductionmentioning

confidence: 99%

“…The method was linear over the concentration range of 25-150µg/ml with coefficient of correlation 0.999. Literature reviewdiscloses that very few different methods were reported for the analysis of ABN in bulk and formulations by fluorescence detection method 18 and RP-HPLC. [19][20] After detailed studies no method was reported to estimate ABN by Ultra Performance Liquid Chromatography (UPLC); hence our present plan is to develop a new, sensitive, economical method for its analysis in bulk and formulation and validated as per ICH norms.…”

Section: Introductionmentioning

confidence: 99%

Quantification and Stability Indicating UPLC Method Development and Validation of Acalabrutinib in Bulk and Pharmaceutical Dosage Form

Goud¹,

Singh²

2021

Int J Life Sci Pharm Res

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Acalabrutinib (ABN) is a Bruton tyrosine kinase inhibitor used to treat mantle cell lymphoma, chronic lymphocytic leukemia and small lymphocytic lymphoma. It has been used in the treatment of Hodgkin lymphoma, multiple myeloma and ovarian cancer. It is available in capsule dosage form, usually prescribed twice a day. The objective of the present study describes the ultra-performance liquid chromatography (UPLC) method development and validation for the estimation of the ABN in Capsule dosage form by following ICH guidelines because no methods were reported in this category. The column and Mobile phase were selected based on trial and error methods. For the estimation, the chromatogram BEH C18 (50 mm x 2.1 mm, 1.7µm) column was run through with Mobile phase 0.01N KH2PO4 : Methanol in the ratio of 50:50 at a flow rate of 0.3 ml/min. Temperature was maintained at 30°C. Optimized wavelength selected for the separation was 234nm. Retention time was achieved 1.148minute in optimized chromatogram. Theoretical plate count and tailing factor were obtained “as per recommendations of ICH limits”. The % RSD precision obtained was 0.7% and Intermediate precision obtained was 0.7% as the limit of Precision was less than 2. %Recovery obtained for marketed formulation was 99.23%. LOD, LOQ values obtained from the regression equation (y=9128.5x + 14854) of ABN were 0.18µg/ml and 0.55µg/ml respectively. Proposed method was linear over the concentration range25-150µg/ml. Different degradation studies (acid, alkali, oxidation, thermal, UV, water) were performed and all these samples passed the limits of degradation. Retention time and run time was decreased, so the method developed was simple and economical that can be adopted in regular quality control tests in Industries.

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

Cited by 20 publications

References 43 publications

Probing the Interaction between Human Serum Albumin and 9-Hydroxyphenanthrene: A Spectroscopic and Molecular Docking Study

Probing the Interaction between Human Serum Albumin and 9-Hydroxyphenanthrene: A Spectroscopic and Molecular Docking Study

Binding mechanism of lipase with Lentinus edodes mycelia polysaccharide by multi‐spectroscopic methods

Quantification and Stability Indicating UPLC Method Development and Validation of Acalabrutinib in Bulk and Pharmaceutical Dosage Form

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