Phase I evaluation of seliciclib (R-roscovitine), a novel oral cyclin-dependent kinase inhibitor, in patients with advanced malignancies

Tourneau, Christophe Le; Faivre, Sandrine; Laurence, Valérie; Delbaldo, Catherine; Vera, Karina; Girre, V.; Chiao, Judy; Armour, Sian; Frame, Sheelagh; Green, Simon R.; Gianella‐Borradori, Athos; Dièras, Véronique; Raymond, Éric

doi:10.1016/j.ejca.2010.08.001

Cited by 150 publications

(80 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…48 Cdk5 is highly expressed in a variety of tumors 47,[50][51][52] and several clinical trials studying the use of roscovitine and other nonselective Cdk5 inhibitors in patients with cancer have either been completed or are ongoing. [60][61][62][63][64][65][66] Our studies demonstrated that the Cdk5-specific inhibitor CIP resulted in a dosedependent reduction in tumor cell proliferation and an increase in the percentage of early apoptotic cells in culture ( Figure 6). The optimal formulation of CIP for in vivo administration has yet to be determined.…”

Section: /2cmentioning

confidence: 99%

Cyclin-dependent kinase 5 activity is required for allogeneic T-cell responses after hematopoietic cell transplantation in mice

Askew

Pareek

Eid

et al. 2017

Blood

View full text Add to dashboard Cite

show abstract

Section: /2cmentioning

confidence: 99%

Cyclin-dependent kinase 5 activity is required for allogeneic T-cell responses after hematopoietic cell transplantation in mice

Askew

Pareek

Eid

et al. 2017

Blood

View full text Add to dashboard Cite

show abstract

“…Emesis and reversible abnormal liver function were also observed. In another phase I clinical trial, one patient with hepatocellular carcinoma showed partial response and six patients achieved tumor (two patients with NSCLC, one with parotid cylindroma, one with corticosurrenaloma, one with thymic carcinoma and one with adenocarcinoma of unknown primary) (Le Tourneau et al 2010). DAEs included nausea, vomiting, asthenia and hypokalemia.…”

Section: Broad-range Inhibitorsmentioning

confidence: 99%

The CDK inhibitors in cancer research and therapy

Cicenas

Valius²

2011

J Cancer Res Clin Oncol

220

176

View full text Add to dashboard Cite

Chemical compounds that interfere with an enzymatic function of kinases are useful for gaining insight into the complicated biochemical processes in mammalian cells. Cyclin-dependent kinases (CDK) play an essential role in the control of the cell cycle and/or proliferation. These kinases as well as their regulators are frequently deregulated in diVerent human tumors. Aberrations in CDK activity have also been observed in viral infections, Alzheimer's, Parkinson's diseases, ischemia and some proliferative disorders. This led to an intensive search for small-molecule CDK inhibitors not only for research purposes, but also for therapeutic applications. Here, we discuss seventeen CDK inhibitors and their use in cancer research or therapy. This review should help researchers to decide which inhibitor is best suited for the speciWc purpose of their research. For this purpose, the targets, commercial availability and IC 50 values are provided for each inhibitor. The review will also provide an overview of the clinical studies performed with some of these inhibitors.

show abstract

“…A single patient with a hepatocellular carcinoma had a partial response and other patients had periods of stable disease. The recommended dose for subsequent studies was concluded to be 1250mg twice per day for 5 days in a 21 day cycle, or 1600mg of Seliciclib twice per day for 3 days in a 14 day cycle [167].…”

Section: Clinical Results From Investigation Of Seliciclib In Clinicamentioning

confidence: 99%

From Roscovitine to CYC202 to Seliciclib – from bench to bedside: discovery and development

Zhelev

Trifonov²,

Wang³

et al. 2013

Biodiscovery

View full text Add to dashboard Cite

This monograph reviews the discovery and development of the cyclindependent kinase inhibitor roscovitine (R-roscovitine, CYC202, Seliciclib). The authors summarise the in vitro and in vivo data that have formed the basis for clinical investigation of Seliciclib as an anti-cancer drug. Kinase selectivity, cellular effects and the pharmacological properties of the drug are discussed in addition to the clinical results of Seliciclib being reviewed. Novel results on the effect of the drug in cardiac hypertrophy are summarized and potential applications of Seliciclib in other therapeutic areas, including, inflammation, virology, glomerulonephritis and polycystic kidney disease, are discussed. Finally the authors argue that optimisation of the therapeutic effect of kinase inhibitors such as Seliciclib can be enhanced using a systems biology approach involving mathematical modelling of the molecular pathways regulating cell growth and division. Seliciclib -discovery and developmentBioDiscovery 2 December 2013 | Issue 10 | 1

show abstract

Phase I evaluation of seliciclib (R-roscovitine), a novel oral cyclin-dependent kinase inhibitor, in patients with advanced malignancies

Cited by 150 publications

References 20 publications

Cyclin-dependent kinase 5 activity is required for allogeneic T-cell responses after hematopoietic cell transplantation in mice

Cyclin-dependent kinase 5 activity is required for allogeneic T-cell responses after hematopoietic cell transplantation in mice

The CDK inhibitors in cancer research and therapy

From Roscovitine to CYC202 to Seliciclib – from bench to bedside: discovery and development

Contact Info

Product

Resources

About