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| Targets |
PHPS1 targets Src homology region 2 domain-containing phosphatase-2 (SHP2). SHP2 is a ubiquitously expressed protein tyrosine phosphatase that regulates growth factor signaling and plays essential roles in development. PHPS1 inhibits SHP2 with a Ki of 0.73 µM and an IC50 of 2.1 µM. It shows selectivity for SHP2 over SHP1 (Ki = 10.7 µM), PTP1B (Ki = 5.8 µM), and PTP1B-Q (Ki = 0.47 µM).
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| ln Vitro |
Erk1/2 phosphorylation is quantitatively regulated by PHPS1 (5–20 μM; 5-360 min), but not by Akt or Stat3 [1]. test for viability[1]
PHPS1 (30 µM; 6 days) inhibits proliferation of human tumor cells. It inhibits Erk1/2 phosphorylation in a dose-dependent manner (5-20 µM; 5-360 minutes) but does not inhibit Akt and Stat3 phosphorylation. PHPS1 also efficiently inhibits activation of Erk1/2 by the leukemia-associated SHP2 mutant SHP2-E76K and blocks the anchorage-independent growth of a variety of human tumor cell lines. It inhibits ECPTP, PTP1B, SHP-1, and mycobacterium MptpA at relatively higher concentrations (IC50s = 5.4, 19, 30, and 39 µM, respectively). |
| ln Vivo |
During the final week of a high-fat diet, PHPS1 (3 mg/kg; i.p.) reduces the risk of atherosclerosis in Ldlr-/-mice [2].
PHPS1 (3 mg/kg; i.p. injection; every day during the last week on a high-fat diet) renders Ldlr-/- mice less susceptible to atherosclerosis development. It has been shown to inhibit SHP-2-dependent cellular signaling and tumor cell colony formation in vivo. By targeting SHP2, PHPS1 modulates signaling pathways involved in cancer progression and immune regulation. |
| Enzyme Assay |
Phosphatase inhibition assays are performed using recombinant SHP2 enzyme and a fluorogenic substrate (e.g., DiFMUP or 6,8-difluoro-4-methylumbelliferyl phosphate). The enzyme is incubated with the substrate in assay buffer (50 mM HEPES pH 7.5, 100 mM NaCl, 1 mM EDTA, 1 mM DTT) at 37°C for 30-60 minutes. The dephosphorylated product generates a fluorescent signal measured at excitation 360 nm, emission 460 nm. PHPS1 is serially diluted and added to the reaction mixture. IC50 and Ki values are determined by non-linear regression analysis. Each concentration is tested in duplicate.
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| Cell Assay |
Viability assay[1]
Cell Types: human cancer cell lines MDA-MB-435, HCT-116 (colon cancer), HCT-15 (colon cancer), PC-3 (prostate cancer) HT-29 (colon cancer), NCI -H661 (lung cancer) and Caki-1 (kidney cancer) Tested Concentrations: 30 μM Incubation Duration: 6 days Experimental Results: Caused a reduction in cell number from 0% (Caki-1) to 74% (HT-29). Western Blot Analysis[1] Cell Types: Madin-Darby canine kidney (MDCK) Cell Tested Concentrations: 5, 10, 20 μM Incubation Duration: 5, 15, 60, 120, 360 minutes Experimental Results: Inhibition of HGF/SF (1 unit/mL )) induces phosphorylation, thereby activating Erk1/2 over a period of 15 minutes to 6 hrs (hours). In contrast, transient phosphorylation of Erk1/2 was unaffected after 5 min. There was no effect on HGF/SF-induced activation of PI3K/Akt or Stat3. Cellular SHP2 inhibition is evaluated in cancer cell lines (e.g., HeLa, MCF-7). Cells are cultured in appropriate media at 37°C with 5% CO2 and treated with PHPS1 at various concentrations (1-50 µM) for 24-72 hours. SHP2 activity in cell lysates is measured using phosphatase assays. Erk1/2 phosphorylation is measured by Western blotting using phospho-specific antibodies. Cell viability and proliferation are assessed using MTT or CellTiter-Glo assays. Each experiment includes known phosphatase inhibitors as positive controls and vehicle controls. |
| Animal Protocol |
Animal/Disease Models: Ldlr-/- (005061) mice[2]
Doses: 3 mg/kg Route of Administration: intraperitoneal (ip) injection; adhere to a high-fat diet every day for the past week. Experimental Results: The size of aortic atherosclerotic plaques was Dramatically diminished compared with the other two groups. In vivo efficacy is evaluated in mouse models, such as atherosclerosis models using Ldlr-/- mice. PHPS1 is administered via intraperitoneal injection at 3 mg/kg daily. Disease progression is monitored by assessing atherosclerotic lesion development. Tissue samples are collected for histopathological analysis. In cancer models, tumor growth is monitored by caliper measurements. Sample sizes typically range from 8-12 animals per group. Detailed protocols are available in the literature. |
| ADME/Pharmacokinetics |
PHPS1 has a molecular weight of 465.44 g/mol and a molecular formula of C21H15N5O6S. Chemical name: 4-{2-[5-(4-nitrophenyl)-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl]diazen-1-yl}benzene-1-sulfonic acid. Solubility: soluble in DMSO. Purity: typically ≥98%. Storage: dry, dark, and -20°C for 1 year. Appearance: solid powder.
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| Toxicity/Toxicokinetics |
Limited toxicology data are available for PHPS1. As a research compound, it is not intended for human use. In animal studies, it is generally well-tolerated at the tested doses (3 mg/kg). Standard toxicology studies would include acute and subchronic toxicity in rodents, genotoxicity screening, and evaluation of effects on the immune system. No clinical trials have been reported for this compound.
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| References |
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| Additional Infomation |
PHPS1 is also known as PTP Inhibitor V and PHPS-1. Its IUPAC name is 4-[(2E)-2-[3-(4-nitrophenyl)-5-oxo-1-phenylpyrazol-4-ylidene]hydrazinyl]benzenesulfonic acid. It is a potent and selective SHP2 inhibitor with a Ki of 0.73 µM. It is a valuable tool for studying SHP2 biology and validating it as a therapeutic target in cancer and immune-related diseases. No clinical trials or regulatory approvals have been reported.
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| Molecular Formula |
C21H15N5O6S
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| Molecular Weight |
465.44
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| Exact Mass |
493.106
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| Elemental Analysis |
C, 54.19; H, 3.25; N, 15.05; O, 20.62; S, 6.89
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| CAS # |
314291-83-3
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| Related CAS # |
PHPS1 sodium;1177131-02-0
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| PubChem CID |
3109390
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| Appearance |
Red to reddish brown solid powder
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| LogP |
4.247
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
33
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| Complexity |
902
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C=CC(=CC=1)/N=N/C1C(N(C2C=CC=CC=2)NC=1C1C=CC(=CC=1)[N+](=O)[O-])=O)(=O)(=O)O
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| InChi Key |
IYPHPQODKSHEHV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H15N5O6S/c27-21-20(23-22-15-8-12-18(13-9-15)33(30,31)32)19(14-6-10-17(11-7-14)26(28)29)24-25(21)16-4-2-1-3-5-16/h1-13,24H,(H,30,31,32)
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| Chemical Name |
4-[[5-(4-nitrophenyl)-3-oxo-2-phenyl-1H-pyrazol-4-yl]diazenyl]benzenesulfonic acid
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| Synonyms |
PHPS-1; PHPS 1; PHPS1
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~53.71 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1485 mL | 10.7425 mL | 21.4850 mL | |
| 5 mM | 0.4297 mL | 2.1485 mL | 4.2970 mL | |
| 10 mM | 0.2149 mL | 1.0743 mL | 2.1485 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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