Current Bioactive Compounds - Volume 7, Issue 1, 2011

PROLOGUE Coupling of low-molecular weight anticancer drugs to synthetic polymers or serum proteins through a cleavable linker has been an effective method for improving their therapeutic index through active and targeting approaches and convincing proofof- concepts have been obtained preclinically for a substantial number of prodrug candidates [1]. Drug conjugates with synthetic polymers or serum proteins th Read More

EZN-2208 (PEG-SN38) is a polymeric prodrug of anticancer agent SN38 (7-ethyl-10-hydroxyl-camptothecin) which is prepared by coupling a 40 kDa, 4-arm polyethylene glycol (PEG) with SN38, through a glycine spacer. The coupling strategy was developed to selectively link the 20-OH group of SN38, thus stabilizing the E-ring of SN38 in the active lactone form. EZN-2208 markedly increased the solubility of SN38 by about 1,000 f Read More

CRLX101 (formerly IT-101) is a first-in-class nanopharmaceutical, currently in Phase 2a development, which has been developed by covalently conjugating camptothecin (CPT) to a linear, cyclodextrin-polyethylene glycol (CDPEG) co-polymer that self-assembles into nanoparticles. As a nanometer-scale drug carrier system, the cyclodextrin polymeric nanoparticle technology, referred to as “CDP”, has unique design featu Read More

XMT-1001 is a conjugate of camptothecin (CPT) and Fleximer®, a biodegradable stealth polymer (poly [1- hydroxymethylethylene hydroxymethylformal], also called PHF). CPT is covalently linked to PHF via a hydrolizable linker. The conjugation of CPT with PHF increases the solubility of CPT. XMT-1001 releases CPT via intermediates camptothecin-20-O-(N-succinimidoglycinate) (CPT-SI) and camptothecin-20-O Read More

ProLindac™ (AP5346) is a 25 kDa polymer delivery vehicle based on hydroxypropylmethacrylamide (HPMA) to which DACH (diaminocyclohexane) platinum is bound. DACH platinum is the active moiety in the approved chemotherapeutic, oxaliplatin. The AP5346 polymer prodrug is currently in phase II clinical development. The polymer targets the drug to tumors and a pH-sensitive linker releases platinum more rapidly in low pH Read More

Hyaluronan receptors (CD44, RHAMM) are over-expressed in a wide variety of cancers including bladder and ovarian tumors. Based on this rationale, a hyaluronic acid paclitaxel conjugate, ONCOFID™-P, was developed for the treatment of refractory bladder cancer and peritoneal carcinosis. ONCOFID™-P has demonstrated improved in vitro and in vivo efficacy in hyaluronan receptor-positive tumor models and a fa Read More

The (6-maleimidocaproyl)hydrazone derivative of doxorubicin (INNO-206, formerly DOXO-EMCH) is a prodrug of the anticancer agent doxorubicin which is selectively bound to the cysteine-34 position of endogenous albumin within a few minutes after intravenous administration planned for 2011. Preclinically as well as clinically, the albuminbound form of INNO-206 has a large AUC, a small volume of distribution and low clear Read More

Urinary tract infections (UTIs) represent a recurrent health problem especially for women. More than 50% of women will suffer from a UTI at least once in their lifetime. Cranberries have long been used for their beneficial effects in preventing symptomatic UTIs in several published studies. However, cranberry products used in these clinical studies do not indicate the amount of active ingredients delivered that help to preven Read More

Triterpenoid alkaloids are one of the most important classes that have been studied. Buxus alkaloids are such a type of triterpenoid alkaloids of cycloartenol skeleton with a degraded C-20 side chain, and with the nitrogen containing substituents at C-3 and/or C-20. 219 Buxus alkaloids have been reported so far. This review article focuses on the structural characters, plant sources and biological activities of Buxus alkaloids. T Read More