Pharmacological Characterization of SDX-7320/Evexomostat: A Novel Methionine Aminopeptidase Type 2 Inhibitor with Anti-tumor and Anti-metastatic Activity.

Methionine aminopeptidase type 2 (METAP2) is a ubiquitous, evolutionarily conserved metalloprotease fundamental to protein biosynthesis which catalyzes removal of the N-terminal methionine residue from nascent polypeptides. METAP2 is an attractive target for cancer therapeutics based upon its over-expression in multiple human cancers, the importance of METAP2-specific substrates whose biological activity may be altered following METAP2 inhibition, and additionally, that METAP2 was identified as the target for the anti-angiogenic natural product, fumagillin. Irreversible inhibition of METAP2 using fumagillin analogues has established the anti-angiogenic and anti-tumor characteristics of these derivatives; however, their full clinical potential has not been realized due to a combination of poor drug-like properties and dose-limiting central nervous system (CNS) toxicity.

First-in-human study of a pharmacological duodenal exclusion therapy shows reduced postprandial glucose and insulin and increased bile acid and gut hormone concentrations.

Aims: To address the need for noninvasive alternatives to metabolic surgery or duodenal exclusion devices for the management of type 2 diabetes (T2D) and obesity by developing an orally administered therapeutic polymer, GLY-200, designed to bind to and enhance the barrier function of mucus in the gastrointestinal tract to establish duodenal exclusion noninvasively.

Materials And Methods: A Phase 1, randomized, double-blind, placebo-controlled, single- (SAD) and multiple-ascending-dose (MAD) healthy volunteer study was conducted. In the SAD arm, four cohorts received a single dose of 0.

Elucidating complex triplet-state dynamics in the model system isopropylthioxanthone.

We introduce techniques for probing the dynamics of triplet states. We employ these tools, along with conventional techniques, to develop a detailed understanding of a complex chemical system: a negative-tone, radical photoresist for multiphoton absorption polymerization in which isopropylthioxanthone (ITX) is the photoinitiator. This work reveals that the same color of light used for the 2-photon excitation of ITX, leading to population of the triplet manifold through intersystem crossing, also depletes this triplet population via linear absorption followed by reverse intersystem crossing (RISC).

2-Colour photolithography.

Photolithography is a crucial technology for both research and industry. The desire to be able to create ever finer features has fuelled a push towards lithographic methods that use electromagnetic radiation or charged particles with the shortest possible wavelength. At the same time, the physics and chemistry involved in employing light or particles with short wavelengths present great challenges.

Sevelamer, a phosphate-binding polymer, is a non-absorbed compound.

Objective: To examine the absorption, distribution and excretion of sevelamer hydrochloride in rats and humans.

Participants: Twelve male Sprague-Dawley rats were used in the animal study, and twenty human volunteers participated in the clinical trial.

Methods: In the animal study, six rats received a single oral dose of [(3)H]sevelamer and six rats were pretreated with unlabelled sevelamer in the diet for 28 days followed by a single dose of [(3)H]sevelamer on day 29.

Determination of the binding parameter constants of Renagel capsules and tablets utilizing the Langmuir approximation at various pH by ion chromatography.

Sevelamer hydrochloride is a cross-linked polymeric amine; it is the active ingredient in Renagel capsules and tablets. Sevelamer hydrochloride is indicated for the control of hyperphosphatemia in patients with end-stage renal disease. The binding parameter constants of sevelamer hydrochloride were determined using the Langmuir approximation for three different dosage forms at pH 4.