5.04293

SRPK Inhibitor, SRPIN340

• 同義詞: 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
• 經驗公式（希爾表示法）: C₁₈H₁₈F₃N₃O
• CAS號碼: 218156-96-8
• 分子量：: 349.35
• MDL號碼: MFCD00116244
• 分類程式碼代碼: 51111800
• NACRES: NA.77

屬性

• 化驗: ≥99% (HPLC)
• 品質等級: 100
• 形狀: powder
• 製造商／商標名: Calbiochem^®
• 儲存條件: OK to freeze; protect from light
• 顏色: light beige
• 溶解度: DMSO: 100 mg/mL
• 儲存溫度: 2-8°C
• SMILES 字串: 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 密鑰: DWFGGOFPIISJIT-UHFFFAOYSA-N

描述

一般說明

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).

包裝

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

重構

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

其他說明

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.

法律資訊

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

安全資訊

• 儲存類別代碼: 11 - Combustible Solids
• 水污染物質分類（WGK）: WGK 3
• 閃點（°F）: Not applicable
• 閃點（°C）: Not applicable