SDZ PSC 833 and SDZ 280–446 are the most active of various resistance-modifying agents in restoring rhodamine-123 retention within multidrug resistant P388 cells

Pourtier-Manzanedo, Albin; Didier, Agnès; C, Muller; Loor, Francis

doi:10.1097/00001813-199208000-00017

Cited by 19 publications

(6 citation statements)

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“…Nevertheless, the overall ranking from strong over weak to none P‐gp inhibition and affinity was: SDZ‐PSC833 > atorvastatin methyl ester atorvastatin lactone > verapamil > simvastatin lactone ∼percnt; lovastatin lactone ∼percnt; atorvastatin acid > pravastatin ∼percnt; fluvastatin. This ranking was comparable for both methods and consistent with results of other groups for known inhibitors ( Pourtier‐Manzanedo et al ., 1992 ).…”

Section: Discussionsupporting

confidence: 90%

“…In order to compare the two above described methods, verapamil and SDZ – PSC833, well‐characterized P‐gp inhibitors ( Pourtier‐Manzanedo et al ., 1992 ), were analysed. Figure 2 shows the concentration‐dependent inhibition of R123 efflux in P388/MDR cells, pre‐incubated with 1 μ M R123, by SDZ – PSC833 and verapamil.…”

Section: Resultsmentioning

confidence: 99%

“…In vitro screening methods for detection of P‐gp affinity are numerous and include primary cell culture systems ( Drewe et al ., 1999 ), fresh tissue ( Fricker et al ., 1999 ), over‐expressing cell lines ( Pourtier‐Manzanedo et al ., 1992 ), membrane vesicles ( Shapiro et al ., 1997 ), purified P‐gp on h.p.l.c. columns ( Zhang et al ., 2000 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

HMG‐CoA reductase inhibitors and P‐glycoprotein modulation

Bogman¹,

Peyer²,

Török³

et al. 2001

British J Pharmacology

182

100

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1 Five 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), (e.g. atorvastatin,¯uvastatin, lovastatin, pravastatin and simvastatin), were investigated for their ability to reverse P-glycoprotein (P-gp) mediated rhodamine 123 (R123) transport in a murine monocytic leukaemia cell line that over-expresses the multi-drug resistance protein 1a/b (mdr1a/1b). 2 P-gp modulation was studied by a¯uorimetric assay and confocal microscopy by means of R123 eux and uptake experiments, respectively. 3 Atorvastatin acid, methyl ester and lactone, lovastatin lactone and simvastatin lactone inhibited R123 transport in a concentration-dependent manner. Lovastatin acid, simvastatin acid,¯uvastatin and pravastatin did not show a signi®cant inhibition of the R123 transport in our cell system. Atorvastatin methyl ester and lactone showed the highest anities for P-gp and results were comparable for both methods. 4 In conclusion, monitoring of R123 transport in living cells by confocal microscopy in addition tō uorimetric assay is a sensitive tool to study P-gp anity in drug screening that is especially useful for early phases of drug development.

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

HMG‐CoA reductase inhibitors and P‐glycoprotein modulation

Bogman¹,

Peyer²,

Török³

et al. 2001

British J Pharmacology

182

100

View full text Add to dashboard Cite

show abstract

“…It should be noted that the use of some P‐gp modulators, especially those belonging to the first generation, has been associated with significant toxicity and side effects (verapamil, cardiotoxicity and cyclosporin A, nephrotoxicity). Observations of impaired biliary and renal excretion mediated by first and second generation MDR modulators are consistent with clinical observations with a variety of MDR modulators and anticancer drugs where increases in anticancer drug plasma exposure (i.e., increased elimination half‐lives and AUC) are hematological toxicities warranted dose reduction 177–184. P‐gp functioning at the BBB led to concern that inhibitors might damage the CNS 80.…”

Section: Clinical Implications Of P‐gp Inhibitionsupporting

confidence: 64%

Enaminones: Exploring Additional Therapeutic Activities

Edafiogho

Kombian

Ananthalakshmi

et al. 2007

Journal of Pharmaceutical Sciences

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“…PSC 833, a non-immunosuppressive cyclosporin is currently being tested as a chemosensitizer in myeloma and other malignancies. 3,10 In this study we show that for ex vivo myeloma cells, CsA, PSC 833, CsG or SDZ 280-446, a semisynthetic cyclopeptolide, 24,25 and some primary CsA and CsG metabolites effectively inhibit P-gp at concentrations expected to be achieved during in vivo infusion of chemosensitizers.…”

Section: Introductionmentioning

confidence: 66%

Drug resistance in multiple myeloma: cyclosporin A analogues and their metabolites as potential chemosensitizers

Pilarski¹,

Rw²,

Murphy³

et al. 1998

Leukemia

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In vivo, cyclosporins are rapidly and almost completely converted to metabolites. AM1 and AM4N, primary metabolites of CsA, mediated inhibition of transport, as did CsG metabolites GM1, GM4N and GM9. AM1 and GM9 are known to reach steady-state in vivo levels that exceed the inhibitory concentration identified here by 1.1-to 1.9-fold. Thus, cyclosporin metabolites, which accumulate in the blood during infusion of CsA and other cyclosporins, are shown here to be effective chemosensitizers for normally drugresistant myeloma cells in vitro. Cyclosporin metabolites are considered to be less toxic than the parent drugs, suggesting that novel chemosensitization strategies designed to minimize concentrations of parent drug and maximize accumulation of primary metabolites in vivo may optimize cytotoxicity to the malignant clone in myeloma.

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SDZ PSC 833 and SDZ 280–446 are the most active of various resistance-modifying agents in restoring rhodamine-123 retention within multidrug resistant P388 cells

Cited by 19 publications

References 0 publications

HMG‐CoA reductase inhibitors and P‐glycoprotein modulation

HMG‐CoA reductase inhibitors and P‐glycoprotein modulation

Enaminones: Exploring Additional Therapeutic Activities

Drug resistance in multiple myeloma: cyclosporin A analogues and their metabolites as potential chemosensitizers

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