Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT


Dubreuil P, Letard S, Ciufolini M, Gros L, Humbert M, Castéran N, Borge L, Hajem B, Lermet A, Sippl W, Voisset E, Arock M, Auclair C, Leventhal PS, Mansfield CD, Moussy A, Hermine O
PLoS ONE - vol. 4 (2009)

BACKGROUND: The stem cell factor receptor, KIT, is a target for the treatment of cancer, mastocytosis, and inflammatory diseases. Here, we characterise the in vitro and in vivo profiles of masitinib (AB1010), a novel phenylaminothiazole-type tyrosine kinase inhibitor that targets KIT.nnMETHODOLOGY/PRINCIPAL FINDINGS: In vitro, masitinib had greater activity and selectivity against KIT than imatinib, inhibiting […]

A High-Throughput Method to Identify Novel Senescene-Inducing Compounds

J Biomol Screen

Ewald JA, Peters N, Desotelle JA, Hoffmann FM, Jarrard DF
J Biomol Screen - vol. 14 853-858 (2009)

Quantitative high-throughput screening identifies inhibitors of anthrax-induced cell death

Bioorganic and Medicinal Chemistry

Zhu PJ, Hobson JP, Southall N, Qiu C, Thomas CJ, Lu J, Inglese J, Zheng W, Leppla SH, Bugge TH, Austin CP, Liu S
Bioorganic and Medicinal Chemistry - vol. 17 5139-5145 (2009)

Here, we report the results of a quantitative high-throughput screen (qHTS) measuring the endocytosis and translocation of a β-lactamase-fused-lethal factor and the identification of small molecules capable of obstructing the process of anthrax toxin internalization. Several small molecules protect RAW264.7 macrophages and CHO cells from anthrax lethal toxin and protected cells from an LF-Pseudomonas exotoxin […]

Nonaminoglycoside compounds induce readthrough of nonsense mutations.

The Journal of experimental medicine

Du L, Damoiseaux R, Nahas S, Gao K, Hu H, Pollard JM, Goldstine J, Jung ME, Henning SM, Bertoni C, Gatti RA
The Journal of experimental medicine - vol. 206 2285-2297 (2009)

Large numbers of genetic disorders are caused by nonsense mutations for which compound-induced readthrough of premature termination codons (PTCs) might be exploited as a potential treatment strategy. We have successfully developed a sensitive and quantitative high-throughput screening (HTS) assay, protein transcription/translation (PTT)-enzyme-linked immunosorbent assay (ELISA), for identifying novel PTC-readthrough compounds using ataxia-telangiectasia (A-T) as a […]

NIH Public Access

Manuscript A, Formation HTF
- vol. 358 1-6 (2009)

Identification and characterization of novel sirtuin inhibitor scaffolds

Bioorganic and Medicinal Chemistry

Sanders BD, Jackson B, Brent M, Taylor AM, Dang W, Berger SL, Schreiber SL, Howitz K, Marmorstein R
Bioorganic and Medicinal Chemistry - vol. 17 7031-7041 (2009)

The sirtuin proteins are broadly conserved NAD+-dependent deacetylases that are implicated in diverse biological processes including DNA recombination and repair, transcriptional silencing, longevity, apoptosis, axonal protection, insulin signaling, and fat mobilization. Because of these associations, the identification of small molecule sirtuin modulators has been of significant interest. Here we report on high throughput screening against […]

The 10th European symposium on calcium-binding proteins in normal and transformed cells.

Biochimica et biophysica acta

Haiech J, Heizmann CW, Krebs J
Biochimica et biophysica acta - vol. 1793 931-2 (2009)

Deciphering the antitumoral activity of quinacrine: Binding to and inhibition of Bcl-xL

Bioorganic and Medicinal Chemistry Letters

Orzáez M, Mondragón L, García-Jareño A, Mosulén S, Pineda-Lucena A, Pérez-Payá E
Bioorganic and Medicinal Chemistry Letters - vol. 19 1592-1595 (2009)

From the screening of a unique collection of 880 off-patent small organic molecules, we have found that quinacrine inhibits the interaction between a BH3 domain-derived peptide and the antiapoptotic protein Bcl-xL. Nuclear magnetic resonance spectroscopy confirmed that quinacrine binds to the hydrophobic groove that Bcl-xL uses for interacting with the BH3 domain of proapoptotic proteins. […]

Chemical genetics reveals bacterial and host cell functions critical for type IV effector translocation by Legionella pneumophila

PLoS Pathogens

Charpentier X, Gabay JE, Reyes M, Zhu JW, Weiss A, Shuman HA
PLoS Pathogens - vol. 5 (2009)

Delivery of effector proteins is a process widely used by bacterial pathogens to subvert host cell functions and cause disease. Effector delivery is achieved by elaborate injection devices and can often be triggered by environmental stimuli. However, effector export by the L. pneumophila Icm/Dot Type IVB secretion system cannot be detected until the bacterium encounters […]

Simulating henipavirus multicycle replication in a screening assay leads to identification of a promising candidate for therapy.

Journal of Virology

Porotto M, Orefice G, Yokoyama CC, Mungall BA, Realubit R, Sganga ML, Aljofan M, Whitt M, Glickman F, Moscona A
Journal of Virology - vol. 83 5148-5155 (2009)

Nipah (NiV) and Hendra (HeV) viruses are emerging zoonotic paramyxoviruses that cause encephalitis in humans, with fatality rates of up to 75%. We designed a new high-throughput screening (HTS) assay for inhibitors of infection based on envelope glycoprotein pseudotypes. The assay simulates multicycle replication and thus identifies inhibitors that target several stages of the viral […]