Ligandability Assessment of IL-1β by Integrated Hit Identification Approaches.

Human interleukin-1β (IL-1β) is a pro-inflammatory cytokine that plays a critical role in the regulation of the immune response and the development of various inflammatory diseases. In this publication, we disclose our efforts toward the discovery of IL-1β binders that interfere with IL-1β signaling. To this end, several technologies were used in parallel, including fragment-based screening (FBS), DNA-encoded library (DEL) technology, peptide discovery platform (PDP), and virtual screening.

Discovery of a selective and biologically active low-molecular weight antagonist of human interleukin-1β.

Human interleukin-1β (hIL-1β) is a pro-inflammatory cytokine involved in many diseases. While hIL-1β directed antibodies have shown clinical benefit, an orally available low-molecular weight antagonist is still elusive, limiting the applications of hIL-1β-directed therapies. Here we describe the discovery of a low-molecular weight hIL-1β antagonist that blocks the interaction with the IL-1R1 receptor.

Blockade of activin type II receptors with a dual anti-ActRIIA/IIB antibody is critical to promote maximal skeletal muscle hypertrophy.

The TGF-β family ligands myostatin, GDF11, and activins are negative regulators of skeletal muscle mass, which have been reported to primarily signal via the ActRIIB receptor on skeletal muscle and thereby induce muscle wasting described as cachexia. Use of a soluble ActRIIB-Fc "trap," to block myostatin pathway signaling in normal or cachectic mice leads to hypertrophy or prevention of muscle loss, perhaps suggesting that the ActRIIB receptor is primarily responsible for muscle growth regulation. Genetic evidence demonstrates however that both ActRIIB- and ActRIIA-deficient mice display a hypertrophic phenotype.

Orthorhombic sphere packings. II. Bivariant lattice complexes.

All homogeneous sphere packings and all interpenetrating layers of spheres were derived that refer to the 22 orthorhombic bivariant lattice complexes. In total, sphere packings of 90 different types have been found. Only for 47 of these types is the maximal inherent symmetry of their sphere packings orthorhombic.

Orthorhombic sphere packings. I. Invariant and univariant lattice complexes.

All homogeneous sphere packings and all interpenetrating sphere packings were derived that refer to the 6 invariant and the 11 univariant lattice complexes belonging to the orthorhombic crystal system. In total, sphere packings of 38 types have been found. Only for 17 types is the maximal inherent symmetry of their sphere packings orthorhombic.

Atrial natriuretic peptide, a regulator of nuclear factor-kappaB activation in vivo.

Natriuretic peptides (NPs) comprise a family of vasoactive hormones that play important roles in the regulation of cardiovascular and renal homeostasis. Along this line, atrial NP (ANP) (international non-proprietary name: carperitide, HANP) is an approved drug for the treatment of acute heart failure. In recent years, evidence has been given that the NP system possesses a far broader biological spectrum than the regulation of blood pressure and volume homeostasis.

Hexagonal and trigonal sphere packings. IV. Trivariant lattice complexes of trigonal space groups.

The 13 trivariant lattice complexes with trigonal symmetry are compatible with 218 types of homogeneous sphere packings, 7 types of interpenetrating sphere packings and one type of interpenetrating layers of spheres. Altogether, the lattice complexes with trigonal characteristic space group (with 0, 1, 2 or 3 degrees of freedom) give rise to 225 types of sphere packing. 110 of these types are compatible exclusively with one of the 13 trivariant lattice complexes, 31 in addition with some of the invariant, univariant or bivariant lattice complexes, whereas 6 types occur solely in such a lattice complex.

Interpenetration of homogeneous sphere packings and of two-periodic layers of spheres.

All systems of interpenetrating sphere packings that occur with highest symmetry in the cubic, hexagonal or tetragonal crystal family are tabulated. Homogeneous sphere packings belonging to 49 different types may be intertwined to systems of interpenetrating sphere packings belonging to 74 types. For all compatible lattice complexes, the coordinate and lattice parameters are given.

Alpha-lipoic acid preconditioning reduces ischemia-reperfusion injury of the rat liver via the PI3-kinase/Akt pathway.

In liver resection and transplantation ischemia-reperfusion injury (IRI) is one of the main causes of organ dys- or nonfunction. The aim of the present study was to determine whether alpha-lipoic acid (LA) is able to attenuate IRI. Rat livers were perfused with Krebs-Henseleit buffer with or without LA (+/-wortmannin), followed by ischemia (1 h, 37 degrees C) and reperfusion (90 min).