PMID- 23588307
OWN - NLM
STAT- MEDLINE
DCOM- 20130829
LR  - 20220408
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Linking)
VI  - 94
IP  - 1
DP  - 2013 Jul
TI  - Hematopoietic stem and progenitor cell mobilization in mice and humans by a 
      first-in-class mirror-image oligonucleotide inhibitor of CXCL12.
PG  - 150-7
LID - 10.1038/clpt.2013.58 [doi]
AB  - NOX-A12 is a PEGylated mirror-image oligonucleotide (a so-called Spiegelmer) that 
      binds to CXCL12 (stromal cell-derived factor-1, SDF-1) with high affinity thereby 
      inhibiting CXCL12 signaling on both its receptors, CXCR4 and CXCR7. In animals, 
      NOX-A12 mobilized white blood cells (WBCs) and hematopoietic stem and progenitor 
      cells (HSCs) into peripheral blood (PB). In healthy volunteers, single doses of 
      NOX-A12 had a benign safety profile and also dose-dependently mobilized WBCs and 
      HSCs into PB. HSC peak mobilization reached a plateau at five times the baseline 
      level at an i.v. dose of 5.4 mg/kg. In accordance with the plasma half-life of 
      38 h, the duration of the WBC and HSC mobilization was long lasting and increased 
      dose-dependently to more than 4 days at the highest dose (10.8 mg/kg). In 
      conclusion, NOX-A12 may be appropriate for therapeutic use in and beyond 
      mobilization of HSCs, e.g., in long-lasting mobilization and chemosensitization 
      of hematological cancer cells.
FAU - Vater, A
AU  - Vater A
AD  - NOXXON Pharma AG, Berlin, Germany. avater@noxxon.com
FAU - Sahlmann, J
AU  - Sahlmann J
FAU - Kroger, N
AU  - Kroger N
FAU - Zollner, S
AU  - Zollner S
FAU - Lioznov, M
AU  - Lioznov M
FAU - Maasch, C
AU  - Maasch C
FAU - Buchner, K
AU  - Buchner K
FAU - Vossmeyer, D
AU  - Vossmeyer D
FAU - Schwoebel, F
AU  - Schwoebel F
FAU - Purschke, W G
AU  - Purschke WG
FAU - Vonhoff, S
AU  - Vonhoff S
FAU - Kruschinski, A
AU  - Kruschinski A
FAU - Hubel, K
AU  - Hubel K
FAU - Humphrey, M
AU  - Humphrey M
FAU - Klussmann, S
AU  - Klussmann S
FAU - Fliegert, F
AU  - Fliegert F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130319
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Oligonucleotides)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Animals
MH  - Chemokine CXCL12/*antagonists & inhibitors/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - *Hematopoietic Stem Cell Mobilization
MH  - Hematopoietic Stem Cells/*metabolism
MH  - Humans
MH  - Leukocyte Count
MH  - Leukocytes/*metabolism
MH  - Macaca
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Models, Animal
MH  - Oligonucleotides/pharmacokinetics/*pharmacology
MH  - Young Adult
EDAT- 2013/04/17 06:00
MHDA- 2013/08/30 06:00
CRDT- 2013/04/17 06:00
PHST- 2013/04/17 06:00 [entrez]
PHST- 2013/04/17 06:00 [pubmed]
PHST- 2013/08/30 06:00 [medline]
AID - clpt201358 [pii]
AID - 10.1038/clpt.2013.58 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2013 Jul;94(1):150-7. doi: 10.1038/clpt.2013.58. Epub 2013 
      Mar 19.