Reversan

Reversan (CBLC4H10) inhibits drug efflux mediated by P-glycoprotein (Pgp) and multidrug resistance protein 1 (MRP1), and exhibits oral activity. Reversan shows activity against glioblastoma multiforme and neuroblastoma models^[1][2]. IC50 & Target:Multidrug resistance-associated protein 1, P-glycoprotein^[1] In Vitro:Reversan (15 μM; 7 h) pre-treatment of A172 and U251 GBM cell lines significantly enhances temozolomide-, vincristine-, and etoposide-induced cell death, as measured by reduced cell viability in MTT assays^[1].
Reversan (15 μM; 7 h) pre-treatment of MZ-327 and MZ-18 primary GBM cell lines significantly enhances temozolomide-, vincristine-, and etoposide-induced cell death, as measured by reduced cell viability in MTT assays^[1].
Reversan (15 μM; 7 h) pre-treatment of MZ-304 and MZ-256 recurrent GBM cell lines significantly enhances temozolomide-, vincristine-, and etoposide-induced cell death, as measured by reduced cell viability in MTT assays^[1].
Reversan (15 μM; 7 h) pre-treatment of U251, MZ-327, and MZ-256 GBM cell lines does not significantly affect cell proliferation rates^[1].
Reversan (15 μM; 7 h) pre-treatment of U251, MZ-327, and MZ-256 GBM cell lines does not significantly alter cell migration as measured by 2D wound closure assays^[1].
Reversan (10 μM; 24 h) induces MRP1 inhibition in MRP1-overexpressing MCF7/VP-LacZ cells, as measured by increased doxorubicin-mediated p53-responsive reporter activity^[2].
Reversan (10 μM; 10 min pre-incubation plus 100 min co-incubation with daunorubicin) selectively increases accumulation of the MRP1 substrate daunorubicin in MRP1-overexpressing MCF7/VP cells but not parental MCF7 cells^[2].
Reversan (5 μM; 18 h co-incubation with chemotherapeutic drugs) selectively sensitizes MRP1-overexpressing MCF7/VP cells to MRP1 substrate drugs, with 14.6-fold sensitization to vincristine, 11.6-fold to etoposide, and 3.8-fold to doxorubicin, but no effect on non-MRP1 substrates^[2].
Reversan (10 μM; 18 h co-incubation with chemotherapeutic drugs) sensitizes multiple MRP1-expressing human tumor cell lines to MRP1 substrate drugs, with the strongest effect in SK-RC45 cells treated with vincristine^[2].
Reversan (10 μM; 18 h co-incubation with substrate drugs) does not inhibit MRP2, MRP3, MRP4, or MRP5, but does inhibit P-gp to significantly sensitize P-gp-overexpressing cells to vincristine^[2].
Reversan (10 μM; 18 h co-incubation with etoposide) is a potent MRP1 inhibitor, increasing MCF7/VP cell sensitivity to etoposide 25-fold and demonstrating 6-8 times greater potency than most tested reference MRP1 modulators^[2]. In Vivo:Reversan (25-100 mg/kg; i.p.; single dose) is non-toxic at single i.p. doses up to 100 mg/kg and Reversan (10 mg/kg; i.p.; daily; 5 consecutive days) does not exacerbate vincristine-induced toxicity in BALB/c mice^[2].
Reversan (10 mg/kg; i.p./p.o.; daily; 5 consecutive days) significantly increases the survival of hMYCN transgenic mice with neuroblastoma when co-administered with vincristine or etoposide, doubling to tripling survival time relative to chemotherapy alone^[2].
Reversan (10 mg/kg; i.p.) in combination with etoposide increases neutrophil counts (protecting against etoposide-induced neutropenia) and enhances etoposide's efficacy against BE(2)-C human neuroblastoma xenografts in nude mice^[2].