PHPS1 (Synonyms: PTP Inhibitor V) |
Katalog-Nr.GC44637
One-Click Copy Product Info
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PHPS1 ist ein potenter und selektiver Shp2-Inhibitor mit Kis von 0,73, 5,8, 10,7, 5,8 und 0,47 μM fÜr Shp2, Shp2-R362K, Shp1, PTP1B bzw. PTP1B-Q.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 314291-83-3
Sample solution is provided at 25 µL, 10mM.
PHPS1 is a cell permeability, phosphotyrosine analog that selectively inhibits Src-homodomain-containing phosphatases (SHP2) with an IC50 value of 2.1µM and a Ki value of 0.73µM[1]. PHPS1 can inhibit SHP2-dependent cell function and tumor cell line growth[2]. PHPS1 can effectively inhibit TGF-β1-induced epithelial-mesenchymal transition in A549 lung epithelial cells[3]. PHPS1 can alleviate airway inflammation and airway hyperresponsiveness in allergic mice[4].
In vitro, treatment of human tumor cell lines (MDA-MB-435, HCT-15, PC-3, HT-29, NCI-H661 cells) with PHPS1 (30µM) for 6 days inhibited the proliferation and colony formation of human tumor cell lines[5].
In vivo, PHPS1 (3mg/kg) administered intraperitoneally to atherosclerotic (AS) mice for one week reduced the number of atherosclerotic plaques without significantly affecting body weight, serum glucose levels, or lipid metabolism, and inhibited the formation of neointima and the proliferation of smooth muscle cells at the aortic root[6]. PHPS1 (15mg/kg) administered intraperitoneally to pancreatic cancer model mice significantly inhibited tumor growth, with the tumor volume in the monotherapy group reduced by approximately 60% compared to the control group[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 RETRACTED ARTICLE: Shp2 positively regulates cigarette smoke-induced epithelial mesenchymal transition by mediating MMP-9 production[J].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.
| Cell experiment [1]: | |
Cell lines | MDA-MB-435、HCT-15、PC-3、HT-29、NCI-H661、Caki-1 cells |
Preparation Method | Cells were treated with a solvent control or 30µM PHPS1 for 6 days. Cell count/standard deviation was determined using a standardized MTT assay. The overall status of these cell lines (untreated) was analyzed by Western blotting using a Shp2-specific antibody. |
Reaction Conditions | 30µM; 6 days |
Applications | PHPS1 inhibits the growth of tumor cells in a Shp2-dependent manner. |
| Animal experiment [2]: | |
Animal models | Ldlr−/− (005061) mice |
Preparation Method | 5 mice were housed in a cage on a 12-h light/dark cycle with free access to water and food. The animals received a high-fat diet containing 1.25% cholesterol for 4 weeks. PHPS1 was dissolved in saline with 0.5% DMSO. 30 mice were randomly divided into three groups: an Atherosclerosis (AS) group, an AS+Vehicle group and an AS+PHPS1 group. Mice in the AS+PHPS1 group received an intraperitoneal (i.p.) injection of 3mg/kg PHPS1 every day during the last week on the high-fat diet, and those in the AS+Vehicle group received an equal volume of saline with 0.5% DMSO on the same days. |
Dosage form | 3mg/kg;7 days; i.p. |
Applications | PHPS1 treatment significantly reduced the atherosclerotic plaque area and inhibited the formation of atherosclerotic plaques. PHPS1 treatment inhibited the proliferation of vascular smooth muscle cells. |
References: | |
| Cas No. | 314291-83-3 | SDF | |
| Überlieferungen | 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 |
| Löslichkeit | 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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 40 reference(s) in Google Scholar.)