5.05763

ProRS Inhibitor, Halofuginone

• 동의어(들): ProRS Inhibitor, Halofuginone, STENOROL, HF, Hydrobromide, prolyl-tRNA synthetase Inhibitor, trans-(±)-7-Bromo-6-chloro-3-[3-(3-hydroxy-2-piperidinyl)-2-oxopropyl]-4(3H)-quinazolinone hydrobromide
• 실험식(Hill 표기법): C₁₆H₁₇BrClN₃O₃ · xHBr
• CAS Number: 64924-67-0
• Molecular Weight: 414.68 (free base basis)
• MDL number: MFCD23843776
• UNSPSC 코드: 12352200
• NACRES: NA.77

속성

• 분석: ≥98% (HPLC)
• Quality Level: 100
• 형태: powder
• 효능: 18 nM IC₅₀
• 제조업체/상표: Calbiochem^®
• 저장 조건: OK to freeze; protect from light
• 색상: white
• solubility: DMSO: 100 mg/mL
• 저장 온도: 2-8°C
• InChI: 1S/C16H17BrClN3O3.BrH/c17-11-6-13-10(5-12(11)18)16(24)21(8-20-13)7-9(22)4-14-15(23)2-1-3-19-14;/h5-6,8,14-15,19,23H,1-4,7H2;1H/t14?,15-;/m1./s1
• InChI key: SJUWEPZBTXEUMU-NUNOUFIPSA-N

설명

일반 설명

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 tRNA^Pro. 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.

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 tRNA^Pro. 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.

생화학적/생리학적 작용

Primary Target
prolyl-tRNA synthetase

포장

Packaged under inert gas

경고

Toxicity: Standard Handling (A)

재구성

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

기타 정보

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.

법적 정보

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

안전성 정보

• 픽토그램: GHS06,GHS09
• 신호어: Danger
• 유해 및 위험 성명서: H300 + H310 + H330 - H315 - H319 - H410
• 예방조치 성명서: P262 - P264 - P273 - P280 - P302 + P352 + P310 - P304 + P340 + P310
• Hazard Classifications: Acute Tox. 1 Dermal - Acute Tox. 2 Inhalation - Acute Tox. 2 Oral - Aquatic Acute 1 - Aquatic Chronic 1 - Eye Irrit. 2 - Skin Irrit. 2
• Storage Class Code: 6.1A - Combustible, acute toxic Cat. 1 and 2 / very toxic hazardous materials
• WGK: WGK 3
• Flash Point (°F): Not applicable
• Flash Point (°C): Not applicable