Abstract: The present application discloses compounds of e.g. formulae (2), (1A), (1B) or (1C) as selective atypical chemokine receptor 3 (ACKR3) modulators for the treatment of e.g. cancer, atherosclerotic vascular disease, cardiovascular diseases, fibrosis (e.g. cardiac fibrosis), inflammatory or autoimmune diseases and conditions, conditions of excessive or abnormal vascularization (e.g. wound healing), stem cell differentiation and mobilization disorders, brain and neuronal dysfunctions (e.g. Alzheimer's disease, multiple sclerosis and demyelinating diseases), kidney dysfunction, renal dysfunction, preeclampsia, human immunodeficiency virus (HIV) infection and obesity. Further provided are said compounds for use in methods for in vitro or ex vivo diagnosis, prediction, prognosis and/or monitoring of a disease or condition characterized by an aberrant level of ACKR3 polypeptide, as well as for use in in vitro methods for identifying an agent useful as a therapeutic. An exemplary compound is e.g. WW-1.

Abstract: The application discloses a specific ACKR2 modulator for use in the treatment of a proliferative disease or disorder in a subject and/or for use in improving the response of a subject to anticancer immunotherapy. The application further discloses pharmaceutical compositions comprising such a specific ACKR2 modulator and one or more immune checkpoint modulators, preferably one or more immune checkpoint inhibitors.

Abstract: The application discloses selective ACKR3 modulating peptides comprising amino acid sequence FGGX1MRRX2 (SEQ ID NO: 1), wherein X1 is F or W; X2 is K, V or F; and wherein the peptides have a length of at most 15 amino acids; fusion proteins comprising the peptides as taught herein; nucleic acids encoding the peptides as taught herein; nucleic acid expression cassettes and vectors comprising the nucleic acid as taught herein; and pharmaceutical compositions comprising the peptide as taught herein or the nucleic acid as taught herein. Further provided are the peptide as taught herein for use as a medicament; methods for in vitro or ex vivo diagnosis, prediction, prognosis and/or monitoring of a disease or condition characterized by an aberrant level of ACKR3 polypeptide using the peptide as taught herein; and in vitro methods for identifying an agent useful as a therapeutic using the peptide as taught herein.

Abstract: The present invention relates to the field of structural biology. More specifically, the present invention relates to novel fusion proteins, their uses and methods in three-dimensional structural analysis of macromolecules, such as X-ray crystallography and high-resolution Cryo-EM, and their use in structure-based drug design and screening. Even more specifically, the invention relates to a functional fusion protein of a cytokine and a scaffold protein wherein the scaffold is a folded protein that interrupts the topology of the cytokine to form a rigid fusion protein that retains its receptor binding and activation capacity. More specifically, chemokine- and interleukin-based functional fusion proteins, and their production and uses, are disclosed herein.