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Biotech / Medical : Biotech Valuation -- Ignore unavailable to you. Want to Upgrade?

To: Henrik who wrote (4252)	7/9/2001 10:59:53 PM
From: scaram(o)uche	Respond to of 52153

Progen (NAZDAQ:PGLAF - ASX:PGL) has seen some upwards price and volume activity both on Nasdaq and in Australia. Not readily apparent......... quote.yahoo.com Heparin binds to a variety of growth factors and facilitates growth factor signaling through specific receptors. At least two such growth factors are angiogenic factors, VEGF and bFGF. If one inhibits the interaction of heparin with these factors, tumor-directed angiogenesis is reduced. However, heparin interacts with a variety of additional "factors", and agents that inhibit such interactions -- in a general fashion -- have been ass'd with toxicity. For background and rationale, Repligen has an ancient project to construct heparin mimetic libraries, with the intent of discovering molecules that selectively inhibit cell activation by VEGF and bFGF. The Progen project? I'm betting against it, and the "market" obviously assigns little faith to the project. The folks at Repligen would be good constructive critics, so you might start there. Clin Appl Thromb Hemost 2001 Apr;7(2):131-40 Anticoagulant and antiprotease profiles of a novel natural heparinomimetic mannopentaose phosphate sulfate (PI-88). Demir M, Iqbal O, Hoppensteadt DA, Piccolo P, Ahmad S, Schultz CL, Linhardt RJ, Fareed J. Loyola University Medical Center, Maywood, IL 60153, USA. Heparinomimetic mannopentaose phosphate sulfate (PI-88) (Progen Industries Ltd. Brisbane, Australia), currently developed as an anticoagulant and antiproliferative agent, mainly is composed of a pentomannan. However, tetrasaccharide and disaccharide components are also present. The molecular profile and the anticoagulant potency of PI-88 are investigated in this study. Gel permeation chromatography and polyacrylamide gel electrophoresis analyses were carried out to determine the molecular profile and separation of components of PI-88, respectively. Potentiation of antithrombin III (ATIII) and heparin cofactor-II (HC-II) activity were measured using chromogenic substrate assay. In order to determine anticoagulant and antiprotease effects of PI-88, various global anticoagulant tests, such as the prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), Hep-test (Haemachem Inc., St. Louis), ecarin clotting time (ECT), activated clotting time (ACT), and thromboelastography (TEG) were used. Anti-Xa and anti-IIa activities also were measured. The effect of PI-88 on the release of tissue factor pathway inhibitor (TFPI) was performed in nonhuman primates who received PI-88 and in endothelial cell culture systems. The relative susceptibility of PI-88 to heparinase I, protamine sulfate (PS), and platelet factor 4 (PF4) also was evaluated. The high-performance liquid chromatography profiles of PI-88 showed that its average molecular weight is approximately 2300 Da. Separation and gradient electrophoretic patterns of PI-88 showed that it is composed of five different fractions. This agent activates HC-II through inhibiting the thrombin generation but not inhibiting ATIII. Although PI-88 produced a concentration-dependent prolongation of all of the clotting tests, ECT gave the best correlation in the dose-response curve (ECT, r2 = 0.94; TT, r2 = 0.84; APTT, r2 = 0.69). Heparinomimetic mannopentaose phosphate sulfate (PI-88) exhibited marked inhibition of FIIa, but not of FXa. Heparinase I failed to produce significant neutralization of PI-88 in all the assays used, whereas PS and PF4 partially neutralized the effects of this compound. Heparinomimetic mannopentaose phosphate sulfate (PI-88) produced fivefold increase in the TFPI levels at 15 minutes after intravenous (IV) injection to primates. The incubation of PI-88 in endothelial cell culture system also showed a strong effect on TFPI release. These results suggest that PI-88 exhibited strong antithrombotic and anticoagulant activity in addition to its known antiproliferative properties. Because of the molecular characteristics and the dual nature of the pharmacologic action of PI-88, this agent represents an attractive pharmacologic agent for the control of thrombotic and proliferative disorders.