2. Academic Validation
  3. Employing a drug repurposing strategy to identify B-cell lymphoma-2 (BCL-2) inhibitors with anticancer potential: An in silico and in vitro based study

Employing a drug repurposing strategy to identify B-cell lymphoma-2 (BCL-2) inhibitors with anticancer potential: An in silico and in vitro based study

  • Bioorg Med Chem. 2025 Aug 20:130:118364. doi: 10.1016/j.bmc.2025.118364.
Ali M Alaseem 1,  Glowi Alasiri 2,  M Arockia Babu 3,  Thakur Gurjeet Singh 4,  Prawez Alam 5,  Mohammad Fareed 6,  Mohammad Suhail Akhter 7,  Nisha Bansal 8
Affiliations

Affiliations

  • 1 Department of Pharmacology, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13317, Saudi Arabia.
  • 2 Department of Biochemistry, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13317, Saudi Arabia.
  • 3 Institute of Pharmaceutical Research, GLA University, Mathura 281406, Uttar Pradesh, India.
  • 4 Centre of Research Impact and Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India.
  • 5 Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi Arabia.
  • 6 Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 13713, Saudi Arabia.
  • 7 MLT department, College of Nursing and Health Sciences, Jazan University, Jizan, Saudi Arabia.
  • 8 Department of Biotechnology, Graphic Era Deemed to be University, Dehradun, Uttarakhand 248002, India. Electronic address: bansalnisha314@gmail.com.
PMID: 40850194 DOI: 10.1016/j.bmc.2025.118364
Abstract

Bcl-2 (B-cell lymphoma-2) is a key protein overexpressed in numerous cancers. Further, its association with Cancer cell survival, prognosis, and ability to evade Apoptosis makes it an important drug target in Cancer chemotherapy. Venetoclax (ABP199) is the only FDA-approved Bcl-2 Inhibitor for chronic lymphocytic leukemia (CLL). Nevertheless, the Bcl-2 active domain mutations, toxicity, and chemoresistance associated with ABP199 further dampen its future efficacy and positive outcome. Considering the gap and quest for rapid drug discovery, we applied the drug repurposing utility on the database of 3584 drugs (HY-L066, from MedChemExpress (MCE)) from sources like USFDA, EMA, NMPA, PMDA, and Pharmacopeia to identify a plausible lead with the potency to inhibit Bcl-2. The HTVS, followed by molecular docking, mechanics using prime MMGB-SA free energy calculations, and MD simulation, led us to identify Stevioside A as a structural lead for the Bcl-2. Stevioside displayed a profound and robust interaction and the binding pose within the receptor catalytic site via hydrogen bonding with the ASP103 (hydroxyl group), GLN99 (via the oxygen atoms), and TYR202. TYR202 was also associated with the π-π stacking with the aromatic ring of stevioside, further stabilizing its orientation and affinity towards the receptor. Furthermore, in western blotting studies, the maximal impact of Stevioside was observed at 750 nM concentration, whereby it halved the Bcl-2 expression in comparison to the untreated control. This response was comparable to the venetoclax. The outcome hence presents a scope to explore Stevioside A and Other top hits in the biological arena and establish their impact as Bcl-2 antagonists.

Keywords

Anticancer; Drug repurposing; Molecular docking; Molecular dynamics; Stevioside.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z