Affiliation: Novartis Institutes for BioMedical Research
- Synthesis and biological evaluation of a potent E-selectin antagonistG Thoma
Novartis Pharma AG, P O Box, CH 4002 Basel, Switzerland, and GlycoTech Corporation, 14915 Broschart Road, Rockville, Maryland 10850, USA
J Med Chem 42:4909-13. 1999..The assays are predictive for the in vivo efficacy of test compounds as indicated by a marked inhibitory effect of 2 in a thioglycollate induced peritonitis model of acute inflammation in mice (ED(50) approximately 15 mg/kg)...
- Synthesis and biological evaluation of a sialyl Lewis X mimic with significantly improved E-selectin inhibitionG Thoma
Novartis Pharma AG, Basel, Switzerland
Bioorg Med Chem Lett 11:923-5. 2001..Furthermore, compound 5 was highly active (IC50 = 10 microM) in a dynamic non-equilibrium assay in which sLe(x) did not inhibit neutrophil rolling at up to 1000 microM...
- Novel glycodendrimers self-assemble to nanoparticles which function as polyvalent ligands in vitro and in vivoGebhard Thoma
Novartis Pharma AG, P O Box, 4002, Basel, Switzerland
Angew Chem Int Ed Engl 41:3195-8. 2002
- Orally bioavailable competitive CCR5 antagonistsGebhard Thoma
Novartis Institutes for BioMedical Research, Lichtstrasse 35, WSJ 507 4 12, CH 4056 Basel, Switzerland
J Med Chem 47:1939-55. 2004..One of these compounds, i.e., 26n, has good PK properties in cynos, and its overall favorable profile makes it a promising candidate for in vivo profiling in transplantation and other disease models...
- The chemokine receptor Cxcr3 is not essential for acute cardiac allograft rejection in mice and ratsH G Zerwes
Autoimmunity, Transplantation and Inflammation, Novartis Institutes for BioMedical Research, Basel, Switzerland
Am J Transplant 8:1604-13. 2008..In summary, Cxcr3 deficiency or pharmacologic blockade does not diminish graft infiltration, tempo and severity of rejection. Thus, Cxcr3 does not appear to play a pivotal role in the allograft rejection models described here...
- Removal of anti-Galalpha1,3Gal xenoantibodies with an injectable polymerAndreas G Katopodis
Novartis Institutes for BioMedical Research, Transplantation Research, Basel, Switzerland
J Clin Invest 110:1869-77. 2002..Furthermore there was no apparent acute or chronic toxicity associated with GAS914 treatment in primates. We conclude that GAS914 may be used therapeutically for the specific removal of alphaGal Ab's...
- Non-covalent polyvalent ligands by self-assembly of small glycodendrimers: a novel concept for the inhibition of polyvalent carbohydrate-protein interactions in vitro and in vivoGebhard Thoma
Novartis Institutes for BioMedical Research, Lichtstrasse 35, 4056 Basel, Switzerland
Chemistry 12:99-117. 2005..The synthesis and characterization of these glycodendrimers is described in detail. Furthermore, we report on the characterization of the non-covalent nanoparticles formed and on their biological evaluation...
- Reduced cardiac side-effect potential by introduction of polar groups: discovery of NIBR-1282, an orally bioavailable CCR5 antagonist which is active in vivoGebhard Thoma
Novartis Institutes for BioMedical Research, Forum 1, Novartis Campus, CH 4002 Basel, Switzerland
Bioorg Med Chem Lett 18:2000-5. 2008..Administration of NIBR-1282 in combination with a non-efficacious dose of CsA led to significant prolongation of kidney allograft survival in cynomolgus monkeys...
- Polymers bearing sLex-mimetics are superior inhibitors of E-selectin-dependent leukocyte rolling in vivoMajid Ali
Cardiovascular Research Group, Clinical Sciences Centre, Northern General Hospital, Sheffield S5 7AU, UK
FASEB J 18:152-4. 2004..In spite of greatly enhanced activity against E-selectin compared with monovalent inhibitor, the multivalent inhibitor had no measurable effect on P- or L-selectin-dependent leukocyte rolling...