5.04293

SRPK Inhibitor, SRPIN340

• 別名: SRPK Inhibitor, SRPIN340, N-(2-Piperidin-1-yl-5-(trifluoromethyl)phenyl)isonicotinamide, Serine-Arginine-Rich Protein Kinase Inhibitor, SR Protein Kinase Inhibitor, SR Protein Phosphorylation Inhibitor 340, (SRPIN)340
• 実験式（ヒル表記法）: C₁₈H₁₈F₃N₃O
• CAS番号: 218156-96-8
• 分子量: 349.35
• MDL番号: MFCD00116244
• UNSPSCコード: 51111800
• NACRES: NA.77

特性

• アッセイ: ≥99% (HPLC)
• 品質水準: 100
• フォーム: powder
• メーカー／製品名: Calbiochem^®
• 保管条件: OK to freeze; protect from light
• 色: light beige
• 溶解性: DMSO: 100 mg/mL
• 保管温度: 2-8°C
• SMILES記法: FC(F)(F)c1cc(c(cc1)N3CCCCC3)NC(=O)c2ccncc2
• InChI: 1S/C18H18F3N3O/c19-18(20,21)14-4-5-16(24-10-2-1-3-11-24)15(12-14)23-17(25)13-6-8-22-9-7-13/h4-9,12H,1-3,10-11H2,(H,23,25)
• InChI Key: DWFGGOFPIISJIT-UHFFFAOYSA-N

詳細

詳細

A cell-permeable isonicotinamide that acts as an ATP-competitive SRPK1-selective inhibitor (IC₅₀ = 0.14 and 1.8 µM, respectively, against mSRPK1 and mSRPK2) with much reduced activity against 143 other kinases. Shown to effectively counteract IGF-1-induced anti-angiogenic to pro-angiogenic VEGF isoforms switch both in cultures in vitro (1 h 10 µM SRPIN340 prior to 12 h IGF-1 stimulation of PCIPs) and in a murine hypoxia-induced retinal neovascularization model in vivo (10 pmol/µL/eye intraocular SRPIN340 injection) by inhibiting PKC/SRPK signaling-dependent, alternate splicing factor ASF- (SF2; splicing factor 2) mediated VEGF pro-mRNA PSS (proximal splice site) selection. Suppresses RNA virus Sindbis propagation (IC₅₀ = 60 µM in Vero cultures) and HCV-JFH1 replication (1 & 10 µM SRPIN340 in Huh7.5.1 cultures). Exhibits no toxicity toward rats (2 g/kg p.o. for 2 wks), CHO (5 mg/mL for 24 h), or Huh7 (30 µM for 48 h).

AA cell-permeable isonicotinamide compound that acts as an ATP-competitive (K_i = 0.89 µM using mSRPK1), SRPK1-selective inhibitor (IC₅₀ = 0.14 and 1.8 µM, respectively, against mSRPK1- or mSRPK2-catalyzed SF2 RS domain peptide phosphorylation) with much reduced or no activity against 143 other kinases, including Clk1 and Clk4, even at concentrations as high as 10 µM. Shown to effectively counteract IGF-1-induced anti-angiogenic to pro-angiogenic VEGF isoforms switch both in cultures in vitro (pro/anti VEGF mRNA ratio = 1.26- and 4.48-times of control ratio, respectively, in 12 h IGF-1 stimulated PCIPs with or without 1 h 10 µM SRPIN340 pretreatment) and in a murine hypoxia-induced retinal neovascularization model in vivo (Relative retinal VEGF mRNA content = 0.3 vs. 1.1, respectively, with or without 10 pmol/µL/eye intraocular SRPIN340 injection upon 48 h room air exposure of 6-day 75% O₂-adopted P12 neonatal mice) by inhibiting PKC/SRPK signaling-dependent, alternate splicing factor ASF- (SF2; splicing factor 2) mediated VEGF pro-mRNA PSS (proximal splice site) selection. Suppresses RNA virus Sindbis propagation (IC₅₀ = 60 µM as determined by virus titre in 4 d-infected Vero cultures) and HCV-JFH1 replication (% HCV core protein-positive Huh7.5.1 48 h post infection = 18.2, 5.9, and 3.0, respectively, with 0. 1. 10 µM SRPIN340; MOI = 0.1). Exhibits no mutagenic effects by Salmonella typhimurium AMES test, nor toxicity toward rats (2 g/kg p.o. for 2 wks), CHO (5 mg/mL for 24 h), or Huh7 (30 µM for 48 h).

包装

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

再構成

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

その他情報

Karakama, Y., et al. 2010. Antimicrob. Agents Chemother.54, 3179.
Nowak, D.G., et al. 2010. J. Biol. Chem.285, 5532.
Fukuhara, T., et al. 2006. Proc. Natl. Acad. Sci. USA103, 11329.

法的情報

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

安全性情報

• 保管分類コード: 11 - Combustible Solids
• WGK: WGK 3
• 引火点(°F): Not applicable
• 引火点(℃): Not applicable