Lysosomal P-gp targeted agent 1 

Lysosomal P-gp targeted agent 1 (Compound 14) is an anti-tumor agent targeting lysosomal P-glycoprotein (Pgp). Lysosomal P-gp targeted agent 1 is selectively transported into lysosomes by overexpressed Pgp, release nitric oxide (NO) to generate reactive oxygen species (ROS), resulting in lysosomal membrane permeabilization (LMP) and inducing apoptosis. Lysosomal P-gp targeted agent 1 can overcome P-glycoprotein-mediated drug resistance and lead to cell cycle arrest, but relatively low toxicity to normal cells. Lysosomal P-gp targeted agent 1 has antitumor activity, significantly inhibits tumor volume^[1].

Lysosomal P-gp targeted agent 1 (48h) has potent anti-Multidrug resistance (MDR) activity against MCF-7/ADR and A549/Taxol cells, exhibits potent antitumor activity against MCF-7/ADR (IC₅₀ = 0.024 μM) and PC-3 cells (IC₅₀ = 3.36 μM), and inhibitory activity and cytotoxicity against drug-resistant A549/Taxol cells (IC₅₀ = 1.43 μM), exhibited toxicity against HepG2 cells (IC₅₀ = 6.57 μM), weak inhibitory activity against MCF-7 cells (IC₅₀ = 21.20 μM) and weak antitumor activity against A549 cells (IC₅₀ =23.75 μM), displays low cytotoxicity to MCF10A (IC₅₀ = 14.32 μM) and BEAS-2B (IC₅₀ = 14.80 μM) cells^[1].
Lysosomal P-gp targeted agent 1 (100 μM) produces higher levels of NO in MCF-7/ADR than in MCF-7 cells, the amounts of NO released intracellularly were associated with their antitumor activity^[1].
Lysosomal P-gp targeted agent 1 (100 nM in MCF-7/ADR, 5 μM in A549/Taxol; 1 h or 3 h ) can be selectively pumped into the lysosomes by overexpressed-Pgp and released NO in a time-dependent manner^[1].
Lysosomal P-gp targeted agent 1 (25 nM, 50 nM, 100 nM in MCF-7 and MCF-7/ADR, 1 μM, 2 μM, 4 μM in A549, A549/Taxol ; 24 h) serves as a Pgp substrate but not regulated Pgp expression^[1].
Lysosomal P-gp targeted agent 1 (25-50 nM) up-regulates the expression of the pro-apoptotic protein Bax and down-regulates the expression of the anti-apoptotic protein Bcl-2 in a concentration-dependent manner, induces the cleavage of PARP1, and up-regulates the expression of caspase-3 and the ratio of PARP1/Cleaved-PARP1, induces apoptosis in MCF-7/ADR cells^[1].
Lysosomal P-gp targeted agent 1 (10-50 nM; 24 h) make the total population of apoptotic cells increased from 8.6 to 65.9% in a dose-dependent manner^[1].
Lysosomal P-gp targeted agent 1 (10-50 nM; 12d) reduces colony growth at 40 and 50 nM, demonstrating their long-term efffcacy against MCF-7/ADR cells^[1].
Lysosomal P-gp targeted agent 1 (20-40 nM; 24 h) interferes with DNA formation and lead to cell cycle arrest^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Lysosomal P-gp targeted agent 1 (1.25-5 mg/kg; i.p.; once every 4 days for 21 days) has antitumor activity, significantly inhibits tumor volume, and tumors are inclined to die or become apoptotic or quiescent, no substantial histological abnormalities or systemic toxicity are detected^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

706.76

C₃₉H₃₄N₂O₉S

3043797-88-9

OC1=CC=C(C=C1OC2=CC=C(C=C2)CCC3=CC=CC(OCCCOC4=NO[N+]([O-])=C4S(=O)(C5=CC=CC=C5)=O)=C3O6)CCC7=CC6=CC=C7

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Sun JY, et al. Design, Synthesis, and Biological Evaluation of Marchantin C-NO Donor Hybrids for Overcoming Pgp-Mediated Drug Resistance by Targeting Lysosome. J Med Chem. 2025 Mar 13;68(5):5503-5528.  [Content Brief]