2. Academic Validation
  3. Olaparib-Cediranib Hybrid as Dual PARP-VEGFR3 Inhibitor Elicits Antitumor Efficacy: Rational Design, Synthesis, Biological Evaluation and Construction of a Charge Convertible pH Responsive Nanoformulation

Olaparib-Cediranib Hybrid as Dual PARP-VEGFR3 Inhibitor Elicits Antitumor Efficacy: Rational Design, Synthesis, Biological Evaluation and Construction of a Charge Convertible pH Responsive Nanoformulation

  • Bioorg Chem. 2025 Oct:165:109035. doi: 10.1016/j.bioorg.2025.109035.
Mandeep Rana 1,  N VijayKamasewara Rao 1,  Zih-Yao Yu 2,  Ram Sharma 1,  Jacob Mathew 3,  Yu-Wen Chen 2,  Sung-Bau Lee 2,  Ankush Bansode 4,  Tai-Ju Hsu 2,  Ajmer Singh Grewal 5,  Chun Hsu Pan 2,  Santosh Guru 4,  Kunal Nepali 6
Affiliations

Affiliations

  • 1 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110031, Taiwan.
  • 2 Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taiwan.
  • 3 Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei 106335, Taiwan.
  • 4 Department of Biological Sciences, National Institute of Pharmaceutical Education and Research, Hyderabad, India.
  • 5 Department of Pharmaceutical Sciences, Guru Gobind Singh College of Pharmacy, Near Guru Nanak Khalsa College, Yamuna Nagar, 135001, Haryana, India.
  • 6 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110031, Taiwan; Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taiwan. Electronic address: nepali@tmu.edu.tw.
PMID: 41056654 DOI: 10.1016/j.bioorg.2025.109035
Abstract

Tempted by the clinical outcomes attained with the combination of poly(ADP-ribose) polymerase (PARP) and vascular endothelial growth factor receptor (VEGFR) inhibitors, a compendium of dual PARP-VEGFR inhibitory assemblages based on structural commonalities of Olaparib (PARP Inhibitor) and Cediranib (VEGFR Inhibitor) was furnished. The aforementioned efforts culminated into a strikingly potent antitumor agent 18 exerting remarkable cell growth inhibitory effects [IC50 = 0.37 μM (HL60); 0.56 μM (A549); 0.80 μM (MDA-MB-231)] through a balanced inhibition of PARP and VEGFR. Specifically, 18 displayed magnificent PARP1, PARP2, and VEGFR3 inhibitory profiles with an IC50 value of 0.0763 nM, 0.0366 nM, and 4.25 nM, respectively. Further, a charge-convertible polymer-based nanoformulation (18-PEG-PLL/DMMA nanoparticles) for targeted drug delivery of 18 was developed. Encouragingly, the nanoformulation demonstrated a cytotoxicity-devoid profile towards normal cells owing to its pH-sensitive behavior and manifested selective cell growth inhibition against solid tumor cells, possibly due to the EPR effect.

Keywords

Leukemia; Lung cancer; Nanoformulation; PARP inhibitors; VEGFR inhibitors.

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