scholarly journals Trafficking modulator TENin1 inhibits endocytosis, causes endomembrane protein accumulation at the pre-vacuolar compartment and impairs gravitropic response in Arabidopsis thaliana

2014 ◽  
Vol 460 (2) ◽  
pp. 177-185 ◽  
Author(s):  
Rupesh Paudyal ◽  
Adam Jamaluddin ◽  
James P. Warren ◽  
Siamsa M. Doyle ◽  
Stéphanie Robert ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Small Molecule ◽  
Protein Trafficking ◽  
Small Molecule Inhibitor ◽  
Protein Accumulation ◽  
Detailed Characterization ◽  
Gravitropic Response ◽  
Vacuolar Compartment ◽  
Molecule Inhibitor

In the present study a detailed characterization of a small molecule inhibitor of protein trafficking and gravitropic response is described. We also identified two Arabidopsis thaliana ecotypes that display resistance to this compound. The ecotypes and chemical provide useful tool to investigate protein trafficking.

398 POSTER Discovery and characterization of a small molecule inhibitor of human Cdc7 kinase

2006 ◽  
Vol 4 (12) ◽  
pp. 122
Author(s):  
C. Santocanale ◽  
A. Montagnoli ◽  
P. Tenca ◽  
M. Menichincheri ◽  
B. Valsasina ◽  
...  
Keyword(s):  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Molecule Inhibitor ◽  
Cdc7 Kinase

scholarly journals Rational design and characterization of a Rac GTPase-specific small molecule inhibitor

2004 ◽  
Vol 101 (20) ◽  
pp. 7618-7623 ◽  
Author(s):  
Y. Gao ◽  
J. B. Dickerson ◽  
F. Guo ◽  
J. Zheng ◽  
Y. Zheng
Keyword(s):  
Small Molecule ◽  
Rational Design ◽  
Small Molecule Inhibitor ◽  
Rac Gtpase ◽  
Molecule Inhibitor

Characterization of BMS-911543, a Functionally Selective Small Molecule Inhibitor of JAK2

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4112-4112 ◽  
Author(s):  
Ashok V Purandare ◽  
Animesh Pardanani ◽  
Theresa McDevitt ◽  
Marco Gottardis ◽  
Terra Lasho ◽  
...  
Keyword(s):  
Small Molecule ◽  
Cell Types ◽  
Small Molecule Inhibitor ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
In Vivo Models ◽  
Molecule Inhibitor ◽  
Transcriptional Changes ◽  
Dose Levels

Abstract Abstract 4112 We report the characterization of BMS-911543, a potent and functionally selective small molecule inhibitor of the Janus kinase family (JAK) member, JAK2. BMS-911543 is a reversible inhibitor of JAK2 with a biochemical IC50 of 0.001 μ M and Ki of 0.48 nM. It has over 74- and 350-fold selectivity against the other JAK family members, JAK3 and JAK1, respectively. Further, examination of > 450 other kinases did not reveal significant inhibitory activity for this JAK2 inhibitor. Functionally, BMS-911543 displayed potent anti-proliferative and pharmacodynamic (PD) effects in mutated JAK2-expressing cell lines dependent upon JAK2-STAT signaling and had little activity in cell types dependent upon other pathways such as JAK1 and JAK3. BMS-911543 was evaluated in colony growth assays using primary progenitor cells isolated from patients with JAK2V617F-positive myeloproliferative disease (MPD) and resulted in an increased anti-proliferative response in MPD cells as compared with those from healthy volunteers. Similar to these in vitro observations, BMS-911543 was also highly active in in vivo models of JAK2-pSTAT signaling in multiple species (mouse, rat, dog and monkey) with sustained pathway suppression being observed after a single oral dose. Additionally, BMS-911543 was evaluated for effects in a JAK2V617F-expressing SET-2 xenograft model system and displayed a minimally effective dose of <2 mg/kg on pSTAT5 pathway suppression, which lasted up to 8 hours. BMS-911543 was also compared to pan-JAK inhibitors in a mouse model of immunosuppression. At low dose levels active in JAK2-dependent PD models, no effects were observed on antigen-induced IgG and IgM production whereas a pan-JAK family inhibitor showed pronounced effects at all dose levels tested. The mechanistic selectivity of BMS-911543 to pan-JAK family inhibitors was extended through comparative analysis of these inhibitors in whole genome gene expression profiling experiments performed in sensitive cell types. In this comparison, BMS-911543 modulated a distinct subset of transcriptional changes as compared to pan-JAK inhibitors, thereby defining a minimal set of transcriptional changes underlying the pharmacologic effects of JAK2 inhibition. Collectively these results define the mechanistic basis for a differential therapeutic index between selective JAK2 and pan-JAK family inhibition pre-clinically and suggest a therapeutic rationale for the further characterization of BMS-911543 in patients with MPD and in other disorders characterized by constitutively active JAK2 signaling. Disclosures: Purandare: Bristol-Myers Squibb: Employment. McDevitt:Bristol-Myers Squibb: Employment. Gottardis:Bristol-Myers Squibb: Employment. You:Bristol-Myers Squibb: Employment. Lombardo:Bristol_Myers Squibb: Employment. Penhallow:Bristol-Myers Squibb: Employment. Vuppugalla:Bristol-Myers Squibb: Employment. Trainor:Bristol-Myers Squibb: Employment. Lorenzi:Bristol-Myers Squibb: Employment.

Pre-clinical characterization of CX-4945, a potent and selective small molecule inhibitor of CK2 for the treatment of cancer

2011 ◽  
Vol 356 (1-2) ◽  
pp. 37-43 ◽  
Author(s):  
Fabrice Pierre ◽  
Peter C. Chua ◽  
Sean E. O’Brien ◽  
Adam Siddiqui-Jain ◽  
Pauline Bourbon ◽  
...  
Keyword(s):  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Molecule Inhibitor

scholarly journals Characterization of EHop-016, Novel Small Molecule Inhibitor of Rac GTPase

2012 ◽  
Vol 287 (16) ◽  
pp. 13228-13238 ◽  
Author(s):  
Brenda L. Montalvo-Ortiz ◽  
Linette Castillo-Pichardo ◽  
Eliud Hernández ◽  
Tessa Humphries-Bickley ◽  
Alina De La Mota-Peynado ◽  
...  
Keyword(s):  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Rac Gtpase ◽  
Molecule Inhibitor
Sign in / Sign up

Export Citation Format

Share Document