174630-04-7

Basic information

• Product Name: REVERSIN 121
• Synonyms: BOC-ASP(OBZL)-LYS(Z)-OTBU;REVERSIN 121
• CAS NO: 174630-04-7
• Molecular Formula: C34H47N3O9
• Molecular Weight: 641.75
• Mol File: 174630-04-7.mol
• Article Data: 2

Chemical Properties

• Appearance: white/powder
• Storage Temp.: −20°C
• Solubility: DMSO or ethanol: soluble
• CAS DataBase Reference: REVERSIN 121(CAS DataBase Reference)
• NIST Chemistry Reference: REVERSIN 121(174630-04-7)
• EPA Substance Registry System: REVERSIN 121(174630-04-7)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 174630-04-7(Hazardous Substances Data)

Usage

Description

Reversin 121 is a hydrophobic peptide chemosensitizer and an analog of reversin, which is a dipeptide derivative. It is known for its ability to reverse P-glycoprotein-mediated multidrug resistance by binding to the P-glycoprotein multidrug transporter (MDR1) with a Kd value of 77 nM. Reversin 121 modulates P-glycoprotein ATPase activity in various systems, including Sf9 insect cell membranes expressing human MDR1, plasma membrane vesicles from multidrug-resistant cells, reconstituted proteoliposomes, and MDR1-expressing intact tumor cells.

Uses

Used in Pharmaceutical Industry:
Reversin 121 is used as a chemosensitizer for overcoming P-glycoprotein-mediated multidrug resistance in cancer treatment. Its ability to bind and modulate the activity of P-glycoprotein helps in enhancing the efficacy of chemotherapeutic drugs, particularly in cases of drug-resistant tumors.
Used in Research Applications:
Reversin 121 is used as a research tool to determine the activity of P-glycoprotein in human retinal pigment epithelium and other cell types. This helps in understanding the mechanisms of multidrug resistance and developing strategies to counteract it in cancer therapy.

Biochem/physiol Actions

Peptide chemosensitizer, inhibitor of P-glycoprotein.

Upstream product

• 5978-22-3 N(ε)-benzoyloxycarbonyl-L-lysine tert-butyl ester hydrochloride 
• 7536-58-5 BOC-L-aspartic acid 4-benzyl ester 

Relevant articles and documents

Synthesis of Poly[ N -(2-hydroxypropyl)methacrylamide] conjugates of inhibitors of the ABC transporter that overcome multidrug resistance in doxorubicin-resistant P388 cells in vitro

The effects of novel polymeric therapeutics based on water-soluble N-(2-hydroxypropyl)methacrylamide copolymers (P(HPMA)) bearing the anticancer drug doxorubicin (Dox), an inhibitor of ABC transporters, or both, on the viability and the proliferation of the murine monocytic leukemia cell line P388 (parental cell line) and its doxorubicin-resistant subline P388/MDR were studied in vitro. The inhibitor derivatives 5-methyl-4-oxohexanoyl reversin 121 (MeOHe-R121) and 5-methyl-4-oxohexanoyl ritonavir ester (MeOHe-RIT), showing the highest inhibitory activities, were conjugated to the P(HPMA) via the biodegradable pH-sensitive hydrazone bond, and the ability of these conjugates to block the ATP driven P-glycoprotein (P-gp) efflux pump was tested. The P(HPMA) conjugate P-Ahx-NH-N=MeOHe-R121 showed a dose-dependent increase in the ability to sensitize the P388/MDR cells to Dox from 1.5 to 24μM, and achieved an approximately 50-fold increase in sensitization at 24μM. The P(HPMA) conjugate P-Ahx-NH-N=MeOHe-RIT showed moderate activity at 6μM (～10 times higher sensitization) and increased sensitization by 50-fold at 12μM. The cytostatic activity of the P(HPMA) conjugate P-Ahx-NH-N=MeOHe-R121(Dox) containing Dox and the P-gp inhibitor MeOHe-R121, both bound via hydrazone bonds to the P(HPMA) carrier, was almost 30 times higher than that of the conjugate P-Ahx-NH-N=Dox toward the P388/MDR cells in vitro. A similar result was observed for P-Ahx-NH-N=MeOHe-RIT(Dox), which exhibited almost 10 times higher cytostatic activity than P-Ahx-NH-N=Dox.