XR 9051 HCl

XR9051 hydrochloride is an orally active and specific modulator of P-glycoprotein-mediated multidrug resistance (MDR)[1].

Research Areas >> Cancer

Signaling Pathways >> Membrane Transporter/Ion Channel >> P-glycoprotein

XR9051 is able to reverse resistance to a variety of cytotoxic drugs, including doxorubicin, etoposide and vincristine, which are associated with classical MDR[1]. XR9051 is highly active and gave at least a 15- to 20- fold decrease in the doxorubicin IC50, in the acquired resistance cell lines[1].

XR9051 (20-40 mg/kg, ip) shows significant modulatory activity in mice bearing MDR human ovarian (2780AD and CH1/DOXr) and SCLC (H69/LX) xenografts[2]. Animal Model: Female Balb/c mice (20-25 g)[2]. Dosage: I.V. Administration: 20 mg/kg at various times (5 min to 24 h). Result: The area under the concentration time curves (AUC) from time 0-∞ for plasma was 11.9 µg. h mL-1. The ratio between AUC for tissue:plasma for liver, heart and brain were 79.6, 16.9 and 0.3 respectively. Animal Model: MDR 2780AD ovarian carcinoma xenografts[2]. Dosage: I.P. Administration: 20, 30, 40 mg/kg daily with Epirubicin i.v. (10 mg/kg). Result: Significantly reduced growth rate of MDR 2780AD ovarian carcinoma xenografts compared with either drug alone.

[1]. I L Dale , et al. Reversal of P-glycoprotein-mediated multidrug resistance by XR9051, a novel diketopiperazine derivative. Br J Cancer. 1998 Oct;78(7):885-92.  

[2]. P Mistry, et al. In vivo efficacy of XR9051, a potent modulator of P-glycoprotein mediated multidrug resistance. Br J Cancer. 1999 Apr;79(11-12):1672-8.