Bovine serum albumin interaction modulates the cellular potency of the BUB1 inhibitor BAY-1816032: fluorescence, molecular docking, and mesothelioma cell evidence
- 1Izmir Biomedicine and Genome Center
Abstract
Albumin binding can substantially alter the unbound concentration and apparent cellular potency of small-molecule anticancer agents. BAY-1816032 is a selective BUB1 kinase inhibitor with activity in malignant pleural mesothelioma, but its interaction with serum albumin has not been defined. This study combined intrinsic bovine serum albumin (BSA) fluorescence measurements, molecular docking, and cell-viability assays to examine whether albumin association influences BAY-1816032 activity. BAY-1816032 produced pronounced quenching of BSA fluorescence at low drug-to-protein molar ratios, and the quenching response was greater at mildly acidic pH than at mildly basic pH. Docking to BSA (PDB 4F5S) placed the top-ranked pose in Sudlow site I (subdomain IIA), with a Vina score of -7.8 kcal/mol and predicted hydrogen-bond contacts with Tyr149, Arg256, and Asp450. In NCI-H28, NCI-H2052, NCI-H2452, and AB12 mesothelioma cells, supplementation of 10% fetal bovine serum medium with 2% (w/v; 20 mg/mL) BSA shifted BAY-1816032 concentration-response curves to the right. Relative to 10% serum alone, IC50 values increased from 2.4 to 11.1 uM in H28, 3.6 to 22.0 uM in H2052, 2.0 to 4.9 uM in H2452, and 2.4 to 11.1 uM in AB12. These data support an albumin-dependent reduction in the freely available drug fraction and identify site I as the leading computational binding-site hypothesis. Because fluorescence-intensity and docking data do not independently establish a dissociation constant or quenching mechanism, direct unbound-fraction measurements and competitive displacement experiments are required for quantitative confirmation.
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BibTeX
@misc{gorjipour2026bovine,
title = {{Bovine serum albumin interaction modulates the cellular potency of the BUB1 inhibitor BAY-1816032: fluorescence, molecular docking, and mesothelioma cell evidence}},
author = {F. Gorjipour and E. Cakiroglu and S. Senturk},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.03.756242},
url = {https://www.biorxiv.org/content/10.64898/2026.10.03.756242v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Bovine serum albumin interaction modulates the cellular potency of the BUB1 inhibitor BAY-1816032: fluorescence, molecular docking, and mesothelioma cell evidence
AU - F. Gorjipour
AU - E. Cakiroglu
AU - S. Senturk
PY - 2026
DA - 2026/10/03
PB - bioRxiv
DO - 10.64898/2026.10.03.756242
UR - https://www.biorxiv.org/content/10.64898/2026.10.03.756242v1
AB - Albumin binding can substantially alter the unbound concentration and apparent cellular potency of small-molecule anticancer agents. BAY-1816032 is a selective BUB1 kinase inhibitor with activity in malignant pleural mesothelioma, but its interaction with serum albumin has not been defined. This study combined intrinsic bovine serum albumin (BSA) fluorescence measurements, molecular docking, and cell-viability assays to examine whether albumin association influences BAY-1816032 activity. BAY-1816032 produced pronounced quenching of BSA fluorescence at low drug-to-protein molar ratios, and the quenching response was greater at mildly acidic pH than at mildly basic pH. Docking to BSA (PDB 4F5S) placed the top-ranked pose in Sudlow site I (subdomain IIA), with a Vina score of -7.8 kcal/mol and predicted hydrogen-bond contacts with Tyr149, Arg256, and Asp450. In NCI-H28, NCI-H2052, NCI-H2452, and AB12 mesothelioma cells, supplementation of 10% fetal bovine serum medium with 2% (w/v; 20 mg/mL) BSA shifted BAY-1816032 concentration-response curves to the right. Relative to 10% serum alone, IC50 values increased from 2.4 to 11.1 uM in H28, 3.6 to 22.0 uM in H2052, 2.0 to 4.9 uM in H2452, and 2.4 to 11.1 uM in AB12. These data support an albumin-dependent reduction in the freely available drug fraction and identify site I as the leading computational binding-site hypothesis. Because fluorescence-intensity and docking data do not independently establish a dissociation constant or quenching mechanism, direct unbound-fraction measurements and competitive displacement experiments are required for quantitative confirmation.
ER -