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505763
Sigma-AldrichProRS Inhibitor, Halofuginone - CAS 64924-67-0 - Calbiochem
A cell-permeable racemic mixture of Halofuginone that inhibits of prolyl-tRNA synthetase.
More>>A cell-permeable racemic mixture of Halofuginone that inhibits of prolyl-tRNA synthetase. Less<<
MSDS (material safety data sheet) or SDS, CoA and CoQ, dossiers, brochures and other available documents.
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Description
Overview
A cell-permeable racemic mixture of Halofuginone whose D-(+)/(2R, 3S) enantiomer serves as the active inhibitor against ProRS-mediated aminoacylation by simultaneously preventing ProRS-catalyzed Pro-AMP formation and the subsequent Pro transfer from Pro-AMP to tRNAPro. Proline, but not other NEAA, is able to reverse the inhibitory effect of HF in in vitro rabbit reticulocyte lysate translations (1 µM HF; 1 mM Pro) and prevent HF-induced cellular AAR pathway activation (100 nM HF/2 mM Pro/MEF; 10 nM HF/1 mM Pro/Murine CD4+ CD25- T cells). Shown to inhibit bFGF-induced neovascularization in a murine corneal angiogenesis model (5 mg/kg/d via food intake) and significantly reduce the severity of MOG33-55-induced EAE in mice (2 µg/mouse/d i.p.) in vivo. Unlike AA-AMP mimetics, HF does not compete against ATP for ProRS binding.
Zhou, H., et al. 2013, Nature494, 121. Keller, T.L., et al. 2012, Nat. Chem. Biol.12, 311. Sundrud, M.S., et al. 2009, Science324, 1334. Elkin, M., et al. 2000, FASEB J.14, 2477. Elkin, M., et al. 1999, Clin. Cancer Res.5, 1982.
Zhou, H., et al. 2013, Nature494, 121. Keller, T.L., et al. 2012, Nat. Chem. Biol.12, 311. Sundrud, M.S., et al. 2009, Science324, 1334. Elkin, M., et al. 2000, FASEB J.14, 2477. Elkin, M., et al. 1999, Clin. Cancer Res.5, 1982.
Data Sheet
Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.
A cell-permeable racemic mixture of Halofuginone, a halogenated derivative of the Dichroa febriguga alkaloid Febrifugine, whose D-(+)/(2R, 3S) enantiomer serves as the active inhibitor against ProRS- (prolyl-tRNA synthetase) mediated aminoacylation by simultaneously targeting/blocking ProRS Proline-binding pocket with its hydroxypiperidine and tRNA 3′ end adenosine-binding site with its halogenated 4-quinazolinone, preventing not only ProRS-catalyzed prolyl adenylation (Pro-AMP formation), but also the subsequent Pro transfer from Pro-AMP to tRNAPro. Consistently, only proline, but not other NEAA, is able to reverse the inhibitory effect of HF in in vitro rabbit reticulocyte lysate translations (1 µM HF; 1 mM Pro) and prevent HF-induced cellular AAR (amino acid response) pathway activation (100 nM HF/2 mM Pro/MEF; 10 nM HF/1 mM Pro/Murine CD4+ CD25- T cells). Shown to inhibit bFGF-induced neovascularization in a murine corneal angiogenesis model (5 mg/kg/day via food intake) and significantly reduce the severity of myelin antigen MOG33-55-induced autoimmune EAE/encephalomyelitis in mice (2 µg/mouse/day i.p.) in vivo. Unlike AA-AMP mimetics, HF does not compete against ATP for ProRS binding. ATP, in its ProRS bound state, actually helps stabilize HF via hydrogen bond interactions.
Form
White powder
Intert gas (Yes/No)
Packaged under inert gas
CAS number
64924-67-0
Chemical formula
C₁₆H₁₇BrClN₃O₃•HBr
Structure formula
Purity
≥98% by HPLC
Solubility
DMSO (100 mg/ml)
Storage
Protect from light
+2°C to +8°C
Do Not Freeze
Ok to freeze
Special Instructions
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Toxicity
Standard Handling
References
Zhou, H., et al. 2013, Nature494, 121. Keller, T.L., et al. 2012, Nat. Chem. Biol.12, 311. Sundrud, M.S., et al. 2009, Science324, 1334. Elkin, M., et al. 2000, FASEB J.14, 2477. Elkin, M., et al. 1999, Clin. Cancer Res.5, 1982.