Phase 1 Trial of Orally Administered Pentosan Polysulphate (Pps) in Patients With Advanced Malignancies

Chronic Progression of Tubulointerstitial Damage in Proteinuric Renal Disease Is Mediated by Complement Activation

“…Polysaccharide pentosan polysulfate has been shown to prevent complement-mediated myocardial injury in the rabbit isolated perfused heart model (54). Unlike other glycosaminoglycans, it is orally bioavailable and has undergone phase I testing as an orally administered drug in patients with advanced cancer (55). Compound 7 (based on the structure of FUT-175 or nafamostat mesilate), a newly synthesized inhibitor of active center-directed trypsinlike serine proteases such as C1r and C1s, has been reported to exhibit greater potency and stability in vivo than FUT-175 as an inhibitor of both the classical and alternative complement activation pathways (56).…”

A novel role of fibroblast growth factor-2 and pentosan polysulfate in the pathogenesis of intestinal bleeding in mice

“…In addition, children affected with the hemolytic uremic syndrome show high levels of circulating FGF-2 (23,24) and are at high risk of intestinal bleeding. Thus these findings might have wider clinical implications for patients treated systemically with PPS and other heparinoids for angiogenic tumors, ulcers, and intestinal inflammatory-angiogenic disorders (5,16,30,34). In contrast, patients treated orally with PPS for cystitis are not likely to be at higher risk of bleeding, since FGF-2 is not accumulated in the bladder, and PSS given orally should not induce anticoagulant changes in the bladder.…”

“…Pentosan polysulfate (PPS), a semisynthetic sulfated heparinoid polysaccharide, can antagonize the binding of FGF-2 to its cell surface receptors and has been shown to modulate the angiogenic activity of FGF-2 in human and mouse tumors (16,22,30,34). However, its use as an antiangiogenic agent in humans is limited by its heparin-like anticoagulant activity, which leads to the development of bleeding disorders in several tissues, including the intestine (16,22).…”

“…However, its use as an antiangiogenic agent in humans is limited by its heparin-like anticoagulant activity, which leads to the development of bleeding disorders in several tissues, including the intestine (16,22). To date, the mechanism by which PPS induces intestinal bleeding in humans remains unclear.…”

Complement Inhibitors And Glomerulonephritis

“…Several have been developed, including synthetic, low-molecular weight molecules such as compastatin, a C3-binding peptide that inhibits C3 activation and generation of C5a and C5b-9 (19), and polysaccharide pentosan sulfate (PPS), which inhibits the alternative complement pathway and generation of C5b-9 (20). Because of their size, both of these may be effective orally, and PPS is now in clinical trial in cancer patients (21). But neither has been tested in kidney disease.…”