title: Stem cell mobilizers targeting chemokine receptor CXCR4: renoprotective application in acute kidney injury.
abstract: We have discovered a novel series of quinazoline-based CXCR4 antagonists. Of these, compound 19 mobilized CXCR4(+) cell types, including hematopoietic stem cells and endothelial progenitor cells, more efficiently than the marketed 1 (AMD3100) with subcutaneous administration at the same dose (6 mg/kg) in mice. This series of compounds thus provides a set of valuable tools to study diseases mediated by the CXCR4/SDF-1 axis, including myocardial infarction, ischemic stroke, and cancer metastasis. More importantly, treatment with compound 19 significantly lowered levels of blood urea nitrogen and serum creatinine in rats with renal ischemia-reperfusion injury, providing evidence for its therapeutic potential in preventing ischemic acute kidney injury. CXCR4 antagonists such as 19 might also be useful to increase circulating levels of adult stem cells, thereby exerting beneficial effects on damaged and/or inflamed tissues in diseases that currently are not treated by standard approaches.
authors: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes , Miaoli, Miaoli County 35053, Taiwan R.O.C.
authors: Chien-Huang
authors: CH
authors: Wu
authors: Jen-Shin
authors: JS
authors: Song
authors: Kuei-Hua
authors: KH
authors: Chang
authors: Jiing-Jyh
authors: JJ
authors: Jan
authors: Chiung-Tong
authors: CT
authors: Chen
authors: Ming-Chen
authors: MC
authors: Chou
authors: Kai-Chia
authors: KC
authors: Yeh
authors: Ying-Chieh
authors: YC
authors: Wong
authors: Chen-Tso
authors: CT
authors: Tseng
authors: Szu-Huei
authors: SH
authors: Wu
authors: Ching-Fang
authors: CF
authors: Yeh
authors: Chung-Yu
authors: CY
authors: Huang
authors: Min-Hsien
authors: MH
authors: Wang
authors: Amit A
authors: AA
authors: Sadani
authors: Chun-Ping
authors: CP
authors: Chang
authors: Chia-Yi
authors: CY
authors: Cheng
authors: Lun K
authors: LK
authors: Tsou
authors: Kak-Shan
authors: KS
authors: Shia
mesh_terms: D058186:Acute Kidney Injury / Q000517:prevention & control*; D000818:Animals; D002633:Chemotaxis / Q000187:drug effects*; D005434:Flow Cytometry; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011799:Quinazolines / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D015427:Reperfusion Injury / Q000517:prevention & control*; D015398:Signal Transduction; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C000598572:N2-(1-(3-(3-cyclohexylaminopropylamino)propyl)-1H-(1,2,3)triazol-4-ylmethyl)-N4-piperidin-4-ylquinazoline-2,4-diamine; D011799:Quinazolines; D019718:Receptors, CXCR4; D014230:Triazoles