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.
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- CAS No.: 3043797-88-9
- Formula: C39H34N2O9S
- Molecular Weight:706.76
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Biological Activity
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.
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Cell Line:MCF-7/ADR
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Concentration:10, 25, 50 nM
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Incubation Time:24 h
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Result:Population of apoptotic cells increased from 8.6 to 65.9% in a dose-dependent manner.
Up-regulated the expression of the pro-apoptotic protein Bax and down-regulated the expression of the anti-apoptotic protein Bcl-2 in a concentration-dependent manner.
Induced the cleavage of PARP1, and up-regulated the expression of caspase-3 and the ratio of PARP1/Cleaved-PARP1.
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Cell Line:MCF-7/ADR
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Concentration:10, 20, 40, 50 nM
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Incubation Time:12 d
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Result:Significantly reduced colony growth at 40 and 50 nM, demonstrated their long-term efficacy against MCF-7/ADR cells.
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Cell Line:MCF-7/ADR
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Concentration:20, 30, 40 nM
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Incubation Time:24 h
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Result:The number of cells in the G2/M phase changed from 11.2 to 18.1, 20.3, and 25.3% in dose-dependent manner.
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Cell Line:MCF-7, MCF-7/ADR, A549, A549/Taxol
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Concentration:25 nM, 50 nM, 100 nM in MCF-7 and MCF-7/ADR, 1 μM, 2 μM, 4 μM in A549, A549/Taxol
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Incubation Time:24 h
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Result:Served as a Pgp substrate but not regulated Pgp expression.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female BALB/c nude mice (weighing 18-20 g, 4-5 weeks) (established xenograft model using human MDR cell line A549/Taxol)[1]
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Dosage:1.25, 2.5, 5 mg/kg
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Administration:Intraperitoneal injection (i.p.), Once every 4 days for 21 days
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Result:Had antitumor activity, significantly inhibited tumor volume (62.7% decrease at 5 mg/kg)
Observed numerous cellular destruction and decreased Ki67 expression in a dose-dependent manner, suggesting that the tumors were inclined to die or become apoptotic or quiescent.
No substantial histological abnormalities or systemic toxicity were detected in the low-, medium-, and high-dose groups.
Chemical Information
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CAS No. 3043797-88-9
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Molecular Weight 706.76
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Formula C39H34N2O9S
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SMILES
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
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Lysosomal P-gp targeted agent 1 Related Classifications
HY-168953 Related Classifications
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