Abstract: The invention is based on a method of modulating the activation or inhibition of Mixed lineage kinase domain-like (MLKL) protein, or a MLKL variant protein, via modulating the intramolecular interaction between the C-terminal helix (Hc) of the psK domain and a hydrophobic groove in the MLKL protein. The invention provides methods and compounds for to selectively target the herein firstly disclosed intramolecular interaction of MLKL protein. Based on the herein disclosed essential intramolecular rearrangement of MLKL, the invention provides small molecules capable of specifically inhibiting mouse or human MLKL. The invention provides uses, including medical applications such as treatments, of MLKL driven conditions including necroptosis, cell trafficking, pathological immune responses and/or inflammation.

Abstract: The invention provides novel treatments (methods, uses and compositions) for treating inflammatory disease based on administering to the subject a combination of at least three agents targeting multiple death-receptor inducing systems, the combination comprising: (1) a first agent that neutralises the receptor TNFR1 or a ligand thereof; and (2) a second agent that neutralises either of: (2a) TRAIL-R, or a ligand thereof; or (2b) CD95, or a ligand thereof; and: (3) a third agent that neutralises any of: (3a) TLR3, or TLR4, or a ligand of either; or (3b) a further, different, receptor which is a TNF Receptor superfamily member shown in Table 1, or a ligand thereof; (3c) Caspase; (3d) RIPK1.

Abstract: The present invention relates to methods and materials for treating an individual with KRAS-mutated cancer or a cancer in which ROCK is inhibited independently of mutated KRAS. The invention is based on the prevention or disruption of the binding of TRAIL-Receptor to its ligand, TRAIL, in vivo, for example by use of an agent that neutralizes TRAIL and/or a the TRAIL-Receptor (such TRAIL-R2) and/or diminishes TRAIL/TRAIL-Receptor activity, thereby reducing cancer cell transformation, migration and metastasis, prolonging survival of patients.

Abstract: The present invention relates to methods and materials for treating an individual with KRAS-mutated cancer or a cancer in which ROCK is inhibited independently of mutated KRAS. The invention is based on the prevention or disruption of the binding of TRAIL-Receptor to its ligand, TRAIL, in vivo, for example by use of an agent that neutralises TRAIL and/or a the TRAIL-Receptor (such TRAIL-R2) and/or diminishes TRAIL/TRAIL-Receptor activity, thereby reducing cancer cell transformation, migration and metastasis, prolonging survival of patients.

Abstract: The present invention relates to an agent for use as a modulator of apoptosis-factor-associated cell death, apoptosis, cell survival, migration and/or proliferation, a method of diagnosing or monitoring apoptosis-factor-associated conditions or disorders as well as a method of identifying a modulator of apoptosis-factor-associated cell death, apoptosis, cell survival, migration and/or proliferation. Preferably, the invention relates to TRAIL-induced cell death and/or TRAIL-induced apoptosis. Preferably the agents are used to stimulate and/or enable TRAIL-induced cell death or to inhibit TRAIL-induced cell death. The preferable use of the diagnostic tools is to diagnose sensitivity or resistance to TRAIL-induced cell death or induction of sensitivity or resistance to TRAIL-induced cell death by an agent.

Abstract: The invention relates to fusion proteins comprising at least a first domain and a second domain selected from a constant Fc immunoglobulin domain; wherein there is at least one amino acid overlap between the first domain and the second domain in the fusion region. In a preferred embodiment of the invention, the first domain is a ligand-binding receptor domain comprising the extra-cellular domain of a membrane-anchored receptor or a ligand-binding fragment thereof.

Abstract: The invention relates to fusion proteins comprising at least a first domain and a second domain selected from a constant Fc immunoglobulin domain.

Abstract: A protein designated TRAIL receptor binds the protein known as TNF-Related Apoptosis-Inducing Ligand (TRAIL). The TRAIL receptor finds use in purifying TRAIL or inhibiting activities thereof. Isolated DNA sequences encoding TRAIL-R polypeptides are provided, along with expression vectors containing the DNA sequences, and host cells transformed with such recombinant expression vectors. Antibodies that are immunoreactive with TRAIL-R are also provided.

Abstract: A protein designated TRAIL receptor binds the protein known as TNF-Related Apoptosis-Inducing Ligand (TRAIL). The TRAIL receptor finds use in purifying TRAIL or inhibiting activities thereof. Isolated DNA sequences encoding TRAIL-R polypeptides are provided, along with expression vectors containing the DNA sequences, and host cells transformed with such recombinant expression vectors. Antibodies that are immunoreactive with TRAIL-R are also provided.

Abstract: The invention relates to fusion proteins comprising at least a first domain and a second domain selected from a constant Fc immunoglobulin domain.

Abstract: This invention relates to compositions for inhibiting apoptosis, containing one to all components of: (a) an APO-1-inhibiting compound; (b) a compound inhibiting and catching, respectively, the APO-1 ligand; and (c) a compound inhibiting the intracellular APO-1 signalling pathway, the component(s) being not considered foreign in an individual, as well as conventional excipients. Furthermore, this invention relates to compounds suitable for inhibiting apoptosis and having at least one extracellular APO-1 domain and a carrier, the domain(s) and the carrier being not considered foreign in an individual.

Abstract: The present invention relates to a method of monitoring and/or modulating disease-associated activatory procceses which are mediated by caspase-10 or caspase-10 isoforms.

Abstract: A protein designated TRAIL receptor binds the protein known as TNF-Related Apoptosis-Inducing Ligand (TRAIL). The TRAIL receptor finds use in purifying TRAIL or inhibiting activities thereof. Isolated DNA sequences encoding TRAIL-R polypeptides are provided, along with expression vectors containing the DNA sequences, and host cells transformed with such recombinant expression vectors. Antibodies that are immunoreactive with TRAIL-R are also provided.

Abstract: A protein designated TRAIL receptor binds the protein known as TNF-Related Apoptosis-Inducing Ligand (TRAIL). The TRAIL receptor finds use in purifying TRAIL or inhibiting activities thereof. Isolated DNA sequences encoding TRAIL-R polypeptides are provided, along with expression vectors containing the DNA sequences, and host cells transformed with such recombinant expression vectors. Antibodies that are immunoreactive with TRAIL-R are also provided.

Abstract: A protein designated TRAIL receptor binds the protein known as TNF-Related Apoptosis-Inducing Ligand (TRAIL). The TRAIL receptor finds use in purifying TRAIL or inhibiting activities thereof. Isolated DNA sequences encoding TRAIL-R polypeptides are provided, along with expression vectors containing the DNA sequences, and host cells transformed with such recombinant expression vectors. Antibodies that are immunoreactive with TRAIL-R are also provided.