Preclinical toxicity and toxicokinetics of GTI-2040, a phosphorothioate oligonucleotide targeting ribonucleotide reductase R2.

Purpose: GTI-2040, a 20-mer phosphorothioate oligonucleotide, was designed to hybridize to the mRNA sequence of human ribonucleotide reductase R2. GTI-2040 has been shown to inhibit human cancer cell proliferation by downregulation of R2 expression in vitro and to significantly inhibit tumor growth in xenograft models of human cancer in mice. As part of the safety evaluation for human clinical trials, the toxicity and toxicokinetics of GTI-2040 were determined in Sprague-Dawley rats and rhesus monkeys.

Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue.

TH9507, an analogue of human growth hormone-releasing factor (hGRF1-44NH2) minimally modified by addition of a trans-3-hexenoyl moiety to Tyr1 of the amino acid sequence, was found to be resistant to dipeptidyl aminopeptidase-IV deactivation. Compared to natural hGRF1-44NH2, the modification slowed the in vitro degradation of the peptide in rat, dog and human plasma and prolonged the in vivo plasma elimination kinetics of immunoreactive TH9507. Plasma growth hormone and insulin-like growth factor-1 (IGF-1) markedly increased in pigs, rats and dogs after daily repeat intravenous or subcutaneous injections of TH9507 at doses up to 600 microg/kg.

Pulmonary delivery of TH9507, a growth hormone releasing factor analogue, in the dog.

A modified growth hormone releasing factor (GRF; TH9507), a 44 amino acid peptide analogue of natural human growth hormone releasing factor, is being developed for the treatment of age-associated conditions resulting from diminished growth hormone (GH) secretion. The inhalation route of administration is being considered as an alternative to subcutaneous injection. A study was undertaken in dogs to investigate the absorption of TH9507 following pulmonary delivery.

Virulizin(R) - A review of its antineoplastic activity.

Virulizin(R) (registered trademark of Lorus Therapeutics, Inc.) is a novel biological response modifier (BRM) that enhances cell-mediated immune response to tumour cells by direct macrophage activation. The agent, an aqueous solution containing a 5% (w/v) solid material mixture comprised of inorganic salts (95 - 99% of the dry weight) and organic compounds of molecular weight < 3000 Daltons (1 - 5% of the dry weight), is provided as a sterile, injectable formulation.

Virulizin-2gamma, a novel immunotherapeutic agent, in treatment of human pancreatic cancer xenografts.

Virulizin-2gamma, a novel biological response modifier extracted from bovine bile, has shown in clinical studies a significant antitumor activity against pancreatic cancer. We report here the results of preclinical evaluation of Virulizin-2gamma in treatment of human pancreatic cancer xenograft in nude mice. In this in vivo study, 14 daily bolus intraperitoneal administrations of Virulizin-2gamma (0.