397 POSTER A phase I dose escalation and pharmacokinetic study of the novel mitotic checkpoint inhibitor GSK923295A in patients with solid tumors

Fleming, Ronald A.; Holen, Kyle D.; Cyr, Tessa L. St.; Johnson, Bernadette; Gauvin, Jennifer; Lager, Joanne; Williams, Brett; Alberti, Dona; Weber, Benjamin; Chung, Vincent

doi:10.1016/s1359-6349(08)72331-0

European Journal of Cancer Supplements

2008

DOI: 10.1016/s1359-6349(08)72331-0

|View full text |Cite

397 POSTER A phase I dose escalation and pharmacokinetic study of the novel mitotic checkpoint inhibitor GSK923295A in patients with solid tumors

Ronald A. Fleming¹,

Kyle D. Holen²,

Tessa L. St. Cyr³

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2010

2013

Publication Types

Select...

Article2

Relationship

Self Cite0

Independent2

Authors

Journals

Cited by 2 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compound 1 exhibited half-lives in the rat and dog of 1.3 and 2.1 h, respectively. This has translated to dose-proportional PK profile in humans with a mean terminal elimination half-life of ∼12 h. 38 In summary, starting from a fragment based screening hit, benzoic acid 2, SAR studies culminated in the discovery of 1, a highly potent and selective inhibitor of CENP-E. Inhibition of CENP-E with 1 induces mitotic arrest in human tumor cells and tumor regressions in vivo. CENP-E inhibition is expected to have a beneficial effect on cancer therapy, and 1 is being evaluated in human clinical trials for the treatment of cancer.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Discovery of the First Potent and Selective Inhibitor of Centromere-Associated Protein E: GSK923295

Qian

McDonald

Zhou

et al. 2010

ACS Med. Chem. Lett.

View full text Add to dashboard Cite

Inhibition of mitotic kinesins represents a novel approach for the discovery of a new generation of anti-mitotic cancer chemotherapeutics. We report here the discovery of the first potent and selective inhibitor of centromere-associated protein E (CENP-E) 3-chloro-N-{(1S)-2-[(N,N-dimethylglycyl)amino]-1-[(4-{8-[(1S)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl}phenyl)methyl]ethyl}-4-[(1-methylethyl)oxy]benzamide (GSK923295; 1), starting from a high-throughput screening hit, 3-chloro-4-isopropoxybenzoic acid 2. Compound 1 has demonstrated broad antitumor activity in vivo and is currently in human clinical trials.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Discovery of the First Potent and Selective Inhibitor of Centromere-Associated Protein E: GSK923295

Qian

McDonald

Zhou

et al. 2010

ACS Med. Chem. Lett.

View full text Add to dashboard Cite

show abstract

Tumor Environmental Factors Glucose Deprivation and Lactic Acidosis Induce Mitotic Chromosomal Instability – An Implication in Aneuploid Human Tumors

et al. 2013

View full text Add to dashboard Cite

Mitotic chromosomal instability (CIN) plays important roles in tumor progression, but what causes CIN is incompletely understood. In general, tumor CIN arises from abnormal mitosis, which is caused by either intrinsic or extrinsic factors. While intrinsic factors such as mitotic checkpoint genes have been intensively studied, the impact of tumor microenvironmental factors on tumor CIN is largely unknown. We investigate if glucose deprivation and lactic acidosis – two tumor microenvironmental factors – could induce cancer cell CIN. We show that glucose deprivation with lactic acidosis significantly increases CIN in 4T1, MCF-7 and HCT116 scored by micronuclei, or aneuploidy, or abnormal mitosis, potentially via damaging DNA, up-regulating mitotic checkpoint genes, and/or amplifying centrosome. Of note, the feature of CIN induced by glucose deprivation with lactic acidosis is similar to that of aneuploid human tumors. We conclude that tumor environmental factors glucose deprivation and lactic acidosis can induce tumor CIN and propose that they are potentially responsible for human tumor aneuploidy.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

397 POSTER A phase I dose escalation and pharmacokinetic study of the novel mitotic checkpoint inhibitor GSK923295A in patients with solid tumors

Cited by 2 publications

References 0 publications

Discovery of the First Potent and Selective Inhibitor of Centromere-Associated Protein E: GSK923295

Discovery of the First Potent and Selective Inhibitor of Centromere-Associated Protein E: GSK923295

Tumor Environmental Factors Glucose Deprivation and Lactic Acidosis Induce Mitotic Chromosomal Instability – An Implication in Aneuploid Human Tumors

Contact Info

Product

Resources

About