Analysis of roscovitine using novel high performance liquid chromatography and UV-detection method: pharmacokinetics of roscovitine in rat

Vita, Marina; Meurling, Lennart; Pettersson, Tommy; Cruz-Sidén, Mabel; Sidén, Å; Hassan, Manal M.

doi:10.1016/s0731-7085(03)00534-x

Cited by 23 publications

(15 citation statements)

References 13 publications

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“…12). Pharmacokinetic studies of (R)-roscovitine revealed a rather short half-life [30 min in rat (29,30), 1.19 h in mice (31 -34), and 2-5 h in man (35,36)]. Several metabolites have been identified, the major ones result from either rapid loss of the isopropyl group (M1), one or more oxidations (M2-M7), or conjugation of a glucose residue (M8).…”

Section: Introductionmentioning

confidence: 99%

N-&-N, a new class of cell death-inducing kinase inhibitors derived from the purine roscovitine

Bettayeb

Sallam

Ferandin

et al. 2008

Molecular Cancer Therapeutics

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Section: Introductionmentioning

confidence: 99%

N-&-N, a new class of cell death-inducing kinase inhibitors derived from the purine roscovitine

Bettayeb

Sallam

Ferandin

et al. 2008

Molecular Cancer Therapeutics

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“…The present LC-MS-MS method provides higher sensitivity and selectivity compared to previously published method [29].…”

Section: The Lc-ms-ms Methodsmentioning

confidence: 81%

Stability, pKa and plasma protein binding of roscovitine

Vita

Abdel‐Rehim

Nilsson

et al. 2005

Journal of Chromatography B

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“…Vehicle-treated SNx rats received DMSO (1 ml/kg). The plasma concentration of seliciclib was measured by high-performance liquid chromatography [19] (Cyclacel Pharmaceuticals Ltd, UK) from blood samples collected 30 min after seliciclib injection. …”

Section: Methodsmentioning

confidence: 99%

Seliciclib Inhibits Renal Hypertrophy but Not Fibrosis in the Rat following Subtotal Nephrectomy

Nutter¹,

Khwaja

Haylor³

2013

Nephron Exp Nephrol

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Background: 5/6 subtotal nephrectomy (SNx) is a non-immune stimulus used to induce renal fibrosis. The ability of seliciclib, a cyclin-dependent kinase inhibitor, to reduce kidney hypertrophy and extracellular matrix (ECM) deposition has been examined in the SNx rat. Methods: Wistar rats were subjected to SNx under isoflurane anaesthesia. The acute effect of seliciclib 28 mg/kg (5 days) on compensatory renal growth (CRG), kidney protein and DNA was determined. In chronic studies albuminuria, hypertension and GFR were monitored. Ki67, apoptag and α-smooth muscle actin were determined by immunohistochemistry together with Masson's trichrome staining. The effect of a maximum non-hypotensive dose of seliciclib 28 mg/kg (8 weeks) was determined. Results: Acutely, the remnant kidney developed CRG. Seliciclib 28 mg/kg inhibited both CRG by 45% and increased kidney protein by 48% without affecting increased kidney DNA. Chronically, SNx rats developed albuminuria, hypertension, low GFR with increased tubulointerstitial cell proliferation, apoptosis, myofibroblast accumulation and enhanced ECM deposition. Seliciclib 28 mg/kg (8 weeks) had no effect on either renal function or renal pathology. Plasma concentrations of seliciclib exceeded 5 µM throughout the study. Conclusions: Despite inhibition of early renal hypertrophy, a maximum non-hypotensive dose of seliciclib 28 mg/kg had no impact on the progression of kidney fibrosis in the SNx rat.

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Analysis of roscovitine using novel high performance liquid chromatography and UV-detection method: pharmacokinetics of roscovitine in rat

Cited by 23 publications

References 13 publications

N-&-N, a new class of cell death-inducing kinase inhibitors derived from the purine roscovitine

N-&-N, a new class of cell death-inducing kinase inhibitors derived from the purine roscovitine

Stability, pKa and plasma protein binding of roscovitine

Seliciclib Inhibits Renal Hypertrophy but Not Fibrosis in the Rat following Subtotal Nephrectomy

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