PHPS1 (Synonyms: PTP Inhibitor V) |
カタログ番号GC44637
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PHPS1は細胞通過性のホスホチロシン類似物であり、Srcホモドメイン含有ホスファターゼ（SHP2）を選択的に阻害し、IC50値は2.1µMであり、Ki値は0.73µMである。
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Cas No.: 314291-83-3
Sample solution is provided at 25 µL, 10mM.
PHPS1は細胞通過性のホスホチロシン類似物であり、Srcホモドメイン含有ホスファターゼ（SHP2）を選択的に阻害し、IC50値は2.1µMであり、Ki値は0.73µMである[1]。PHPS1はSHP2依存性の細胞機能と腫瘍細胞株の成長を阻害できる[2]。PHPS1はA549肺上皮細胞で、TGF-β1誘発の上皮間葉転換を効果的に阻害できる[3]。PHPS1はアレルギーのマウスで、気道の炎症と過剰反応を軽減できる[4]。
体外で、ヒト腫瘍細胞株（MDA-MB-435、HCT-15、PC-3、HT-29、NCI-H661細胞）をPHPS1（30µM）で6日間処理した結果、ヒト腫瘍細胞株の増殖とコロニーの形成を阻害した[5]。
体内で、動脈硬化性（AS）マウスに、PHPS1（3mg/kg）を1週間腹腔内投与した結果、体重、血清グルコースのレベルまたは脂質代謝を著しく影響せずに、動脈硬化性プラークの数を減らし、大動脈基部で新生内膜の形成、平滑筋細胞の増殖を阻害した[6]。PHPS1（15mg/kg）を膵臓癌モデルマウスに腹腔内投与した結果、腫瘍の成長を著しく阻害し、対照群と比べて、単独療法群における腫瘍の体積は約60%減少した[7]。
References:
[1] Ramamoorthy D. Synthesis of small molecule inhibitors targeting signal transduction pathways[J]. 2009.
[2] Kong J, Long Y Q. Recent advances in the discovery of protein tyrosine phosphatase SHP2 inhibitors[J]. RSC Medicinal Chemistry, 2022, 13(3): 246-257.
[3] Liu Y, Guan Y, Shen J, et al. RETRACTED ARTICLE: Shp2 positively regulates cigarette smoke-induced epithelial mesenchymal transition by mediating MMP-9 production[J]. Respiratory Research, 2020, 21(1): 161.
[4] Xu C, Wu X, Lu M, et al. Protein tyrosine phosphatase 11 acts through RhoA/ROCK to regulate eosinophil accumulation in the allergic airway[J]. The FASEB Journal, 2019, 33(11): 11706.
[5] Hellmuth K, Grosskopf S, Lum C T, et al. Specific inhibitors of the protein tyrosine phosphatase Shp2 identified by high-throughput docking[J]. Proceedings of the National Academy of Sciences, 2008, 105(20): 7275-7280.
[6] Chen J, Cao Z, Guan J. SHP2 inhibitor PHPS1 protects against atherosclerosis by inhibiting smooth muscle cell proliferation[J]. BMC cardiovascular disorders, 2018, 18(1): 72.
[7] Gomes E G, Connelly S F, Summy J M. Targeting the yin and the yang: combined inhibition of the tyrosine kinase c-Src and the tyrosine phosphatase SHP-2 disrupts pancreatic cancer signaling and biology in vitro and tumor formation in vivo[J]. Pancreas, 2013, 42(5): 795-806.
| 細胞実験[1]: | |
細胞株 | MDA-MB-435、HCT-15、PC-3、HT-29、NCI-H661、Caki-1細胞 |
準備方法 | 細胞を溶媒対照物または30µMのPHPS1で6日間処理した。細胞の数/標準偏差を標準MTTアッセイで測定した。これらの細胞株（未処理）の全体的な状態を、Shp2特異性の抗体を使い、ウエスタンブロットで分析した。 |
反応条件 | 30µM；6日間 |
アプリケーション | PHPS1は腫瘍細胞の成長をShp2依存的に阻害する。 |
| 動物実験 [2]: | |
動物モデル | Ldlr−/− (005061)マウス |
準備方法 | 12時間の昼夜循環のケージで、5匹のマウスを飼育し、水と飼料を自由に摂取させた。動物には1.25%のコレステロールを含有する高脂肪食を4週間投与した。0.5% DMSOを含有する生理食塩水でPHPS1を溶解した。30匹のマウスをランダムに三つのグループに分けた：動脈硬化症（AS）群、AS+溶媒群とAS+PHPS1群。AS+PHPS1群のマウスには、高脂肪食の最終週に、3mg/kgのPHPS1を毎日腹腔内（i.p.）注射し、同じ日に、AS+溶媒群のマウスに、0.5% DMSOを含有する等量の生理食塩水を投与した。 |
投与形態 | 3mg/kg；7日間；腹腔内注射 |
アプリケーション | PHPS1の処理は、動脈硬化性プラークの面積を著しく減らし、動脈硬化性プラークの形成を阻害した。PHPS1の処理は、血管平滑筋細胞の増殖を著しく阻害した。 |
References: | |
| Cas No. | 314291-83-3 | SDF | |
| 同義語 | PTP Inhibitor V | ||
| Chemical Name | 4-[2-[1,5-dihydro-3-(4-nitrophenyl)-5-oxo-1-phenyl-4H-pyrazol-4-ylidene]hydrazinyl]-benzenesulfonic acid | ||
| Canonical SMILES | O=C1N(C2=CC=CC=C2)N=C(C3=CC=C([N+]([O-])=O)C=C3)/C1=N\NC4=CC=C(S(O)(=O)=O)C=C4 | ||
| Formula | C21H15N5O6S | M.Wt | 465.4 |
| 溶解度 | 5mg/mL in DMSO, or in DMF | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1487 mL | 10.7434 mL | 21.4869 mL |
| 5 mM | 429.7 μL | 2.1487 mL | 4.2974 mL |
| 10 mM | 214.9 μL | 1.0743 mL | 2.1487 mL |
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 40 reference(s) in Google Scholar.)