Tiplaxtinin, a novel, orally efficacious inhibitor of plasminogen activator inhibitor-1: design, synthesis, and preclinical characterization

H Elokdah, M Abou-Gharbia, JK Hennan… - Journal of medicinal …, 2004 - ACS Publications
Indole oxoacetic acid derivatives were prepared and evaluated for in vitro binding to and
inactivation of human plasminogen activator inhibitor-1 (PAI-1). SAR based on biochemical, …

Enhanced clearance of Aβ in brain by sustaining the plasmin proteolysis cascade

…, TA Comery, RL Martone, H Elokdah… - Proceedings of the …, 2008 - National Acad Sciences
The amyloid hypothesis states that a variety of neurotoxic β-amyloid (Aβ) species contribute
to the pathogenesis of Alzheimer's disease. Accordingly, a key determinant of disease onset …

[HTML][HTML] Mechanism of inactivation of plasminogen activator inhibitor-1 by a small molecule inhibitor

NV Gorlatova, JM Cale, H Elokdah, D Li, K Fan… - Journal of biological …, 2007 - ASBMB
The inactivation of plasminogen activator inhibitor-1 (PAI-1) by the small molecule PAI-1
inhibitor PAI-039 (tiplaxtinin) has been investigated using enzymatic analysis, direct binding …

Pharmacological inhibition and genetic deficiency of plasminogen activator inhibitor-1 attenuates angiotensin II/salt-induced aortic remodeling

…, JP Griffin, DL Crandall, H Elokdah… - … , and vascular biology, 2005 - Am Heart Assoc
… that PAI-039 exhibited a lack of significant toxicity such that the no toxic effect level was
set at a dose of 2000 mg/kg per day, which resulted in a 24- hour exposure of 1508 μg·h/mL, …

Design, synthesis, and biological evaluation of thio-containing compounds with serum HDL-cholesterol-elevating properties

H Elokdah, TS Sulkowski… - Journal of medicinal …, 2004 - ACS Publications
… Animals were fasted for 4 h and dosed the last time 2 h prior to sacrifice. Animals were
weighed prior to collection of blood and liver. Multiple dose studies were performed in the same …

Pivotal role of PAI-1 in a murine model of hepatic vein thrombosis

LH Smith, JD Dixon, JR Stringham, M Eren, H Elokdah… - Blood, 2006 - ashpublications.org
Hepatic veno-occlusive disease (VOD) is a common complication of high-dose chemotherapy
associated with bone marrow transplantation. While the pathogenesis of VOD is uncertain, …

[HTML][HTML] Characterization and comparative evaluation of a structurally unique PAI‐1 inhibitor exhibiting oral in‐vivo efficacy

DL Crandall, H Elokdah, L Di, JK Hennan… - Journal of Thrombosis …, 2004 - Elsevier
Plasminogen activator inhibitor‐1 (PAI‐1) is the major physiological inhibitor of both tissue‐type
plasminogen activator (tPA) and urokinase‐type plasminogen activator (uPA). Elevated …

Efficient one-pot synthesis of substituted 2-amino-1, 3, 4-oxadiazoles

ELP Chekler, HM Elokdah, J Butera - Tetrahedron Letters, 2008 - Elsevier
A convenient one-pot method for the preparation of substituted 2-amino-1,3,4-oxadiazoles
has been developed. The method is a significant improvement over previously reported …

Evaluation of PAI-039 [{1-benzyl-5-[4-(trifluoromethoxy) phenyl]-1H-indol-3-yl}(oxo) acetic acid], a novel plasminogen activator inhibitor-1 inhibitor, in a canine model …

JK Hennan, H Elokdah, M Leal, A Ji… - … of Pharmacology and …, 2005 - ASPET
… 1 h at room temperature. The structure of PAI-039 was previously published under the name
tiplaxtinin (Elokdah et … Based on the pharmacokinetics of PAI-039 and a C max at 1.8 h, we …

[HTML][HTML] Mapping of a conformational epitope on plasminogen activator inhibitor-1 by random mutagenesis: Implications for serpin function

NV Gorlatova, H Elokdah, K Fan, DL Crandall… - Journal of Biological …, 2003 - ASBMB
The mechanism for the conversion of plasminogen activator inhibitor-1 (PAI-1) from the active
to the latent conformation is not well understood. Recently, a monoclonal antibody, 33B8, …