Abstract: The present invention relates to active agents or compounds as well as pharmaceutical compositions comprising said compounds, which are capable of reducing or inhibiting or blocking the enzymatic activity of the glutaminyl-peptide cyclotransferase (QPCT) protein, the glutaminyl-peptide cyclotransferase-like protein (QPCTL) protein, or combinations thereof or are capable of reducing or inhibiting the expression of QPCT gene, the QPCTL gene, or combinations thereof. Also provided are methods for screening or selecting for said compounds. The present invention further relates to a pharmaceutical composition comprising a first active agent for use in a method of treating a condition in a subject that would benefit from reducing the signaling or the binding between SIRP? and CD47 in the subject (e.g. cancer), wherein the method of treating comprises reducing expression or enzymatic activity of QPCTL, QPCT, or combinations thereof in the cell with CD47 on the surface.

Abstract: Disclosed herein is are conjugates that comprise a ubiquitin dimer or multimer, comprising a distal moiety conjugated to a proximal moiety. The distal moiety comprises a polypeptide comprising a distal ubiquitin at its C-terminus, said ubiquitin comprising at least one of the following mutations: K6X, K11X, K27X, K29X, K33X, K48X, K48X, K63X, or K63X, where X is selected from R, A or C. The proximal moiety comprises a polypeptide comprising either a proximal ubiquitin at its C-terminus or a proximal ubiquitin at its N-terminus; said ubiquitin comprising a blocked C-terminus. The distal moiety is conjugated to the proximal moiety via an amide bond from G76 of the distal ubiquitin to one of M1, K6, K11, K27, K29, K33, K48, or K63 of the proximal ubiquitin. Also provided are methods for the production of said conjugates, formulations comprising said conjugates and methods of using said conjugates.

Abstract: The present invention relates to active agents or compounds as well as pharmaceutical compositions comprising said compounds, which are capable of reducing or inhibiting or blocking the enzymatic activity of the glutaminyl-peptide cyclotransferase (QPCT) protein, the glutaminyl-peptide cyclotransferase-like protein (QPCTL) protein, or combinations thereof or are capable of reducing or inhibiting the expression of QPCT gene, the QPCTL gene, or combinations thereof. Also provided are methods for screening or selecting for said compounds. The present invention further relates to a pharmaceutical composition comprising a first active agent for use in a method of treating a condition in a subject that would benefit from reducing the signaling or the binding between SIRP? and CD47 in the subject (e.g. cancer), wherein the method of treating comprises reducing expression or enzymatic activity of QPCTL, QPCT, or combinations thereof in the cell with CD47 on the surface.