title: Derivatives of erythropoietin that are tissue protective but not erythropoietic.
abstract: Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype-selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a potency and efficacy comparable to EPO.
authors.affiliation: H. Lundbeck A/S, 2500 Valby, Denmark.
authors.forename: Marcel
authors.initials: M
authors.lastname: Leist
authors.forename: Pietro
authors.initials: P
authors.lastname: Ghezzi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grasso
authors.forename: Roberto
authors.initials: R
authors.lastname: Bianchi
authors.forename: Pia
authors.initials: P
authors.lastname: Villa
authors.forename: Maddalena
authors.initials: M
authors.lastname: Fratelli
authors.forename: Costanza
authors.initials: C
authors.lastname: Savino
authors.forename: Marina
authors.initials: M
authors.lastname: Bianchi
authors.forename: Jacob
authors.initials: J
authors.lastname: Nielsen
authors.forename: Jens
authors.initials: J
authors.lastname: Gerwien
authors.forename: Pekka
authors.initials: P
authors.lastname: Kallunki
authors.forename: Anna Kirstine
authors.initials: AK
authors.lastname: Larsen
authors.forename: Lone
authors.initials: L
authors.lastname: Helboe
authors.forename: Søren
authors.initials: S
authors.lastname: Christensen
authors.forename: Lars O
authors.initials: LO
authors.lastname: Pedersen
authors.forename: Mette
authors.initials: M
authors.lastname: Nielsen
authors.forename: Lars
authors.initials: L
authors.lastname: Torup
authors.forename: Thomas
authors.initials: T
authors.lastname: Sager
authors.forename: Alessandra
authors.initials: A
authors.lastname: Sfacteria
authors.forename: Serhat
authors.initials: S
authors.lastname: Erbayraktar
authors.forename: Zubeyde
authors.initials: Z
authors.lastname: Erbayraktar
authors.forename: Necati
authors.initials: N
authors.lastname: Gokmen
authors.forename: Osman
authors.initials: O
authors.lastname: Yilmaz
authors.forename: Carla
authors.initials: C
authors.lastname: Cerami-Hand
authors.forename: Qiao-Wen
authors.initials: QW
authors.lastname: Xie
authors.forename: Thomas
authors.initials: T
authors.lastname: Coleman
authors.forename: Anthony
authors.initials: A
authors.lastname: Cerami
authors.forename: Michael
authors.initials: M
authors.lastname: Brines
mesh_terms: D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D002478:Cells, Cultured; D003929:Diabetic Neuropathies / Q000188:drug therapy; D015195:Drug Design; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy; D004920:Erythropoiesis; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006400:Hematocrit; D006801:Humans; D008024:Ligands; D051379:Mice; D008809:Mice, Inbred C3H; D016296:Mutagenesis; D009422:Nervous System Diseases / Q000188:drug therapy*; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017467:Receptors, Erythropoietin / Q000378:metabolism; D011994:Recombinant Proteins; D015398:Signal Transduction; D013117:Spinal Cord Compression / Q000188:drug therapy; D020521:Stroke / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D018696:Neuroprotective Agents; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; C488171:carbamylated erythropoietin; D004921:Erythropoietin