| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
SHP2 (PTPN11), a non-receptor protein tyrosine phosphatase that transduces signals from receptor tyrosine kinases and cytokine receptors to the RAS-ERK pathway. SHP836 is an allosteric inhibitor, stabilizing SHP2 in its inactive closed conformation.
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| ln Vitro |
SHP836 maintains SHP2's active conformation, which prevents the catalytic site from accessing the substrate and blocks it [1].
SHP836 inhibits the phosphatase activity of full-length SHP2 with an IC50 of 12 uM. It downregulates DUSP6 mRNA, a downstream target of the RAS-ERK pathway, indicating pathway inhibition. The compound is a selective allosteric inhibitor of SHP2. By stabilizing the inactive closed conformation of SHP2, it prevents substrate access to the catalytic site. |
| ln Vivo |
In vivo, SHP836 is expected to have antitumor activity by inhibiting SHP2-mediated signaling. It may be used in combination with other targeted therapies (e.g., MEK inhibitors, KRAS G12C inhibitors) to overcome resistance mechanisms in RAS-ERK pathway-driven cancers. Specific in vivo efficacy data are limited.
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| Enzyme Assay |
SHP2 phosphatase activity assay: Recombinant full-length SHP2 (10-20 nM) is incubated with a fluorogenic substrate (e.g., 6,8-difluoro-4-methylumbelliferyl phosphate, DiFMUP, 10-50 uM) and varying concentrations of SHP836 (0.1-1000 uM) in assay buffer (50 mM HEPES pH 7.4, 150 mM NaCl, 5 mM DTT, 0.01% Triton X-100) for 30-60 minutes at 37degC. The increase in fluorescence (excitation 358 nm, emission 455 nm) due to substrate dephosphorylation is measured. IC50 is calculated from dose-response curves.
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| Cell Assay |
Cell signaling assay: Cancer cells (e.g., cells with RTK or RAS pathway activation) are treated with SHP836 (1-100 uM) for 4-24 hours. Cell lysates are prepared and analyzed by Western blot for phosphorylated ERK (p-ERK), total ERK, and other downstream markers to assess pathway inhibition. DUSP6 mRNA levels are measured by qRT-PCR as a pharmacodynamic marker of RAS-ERK pathway inhibition.
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| Animal Protocol |
Mouse xenograft models: SHP836 could be tested in tumor-bearing mice (e.g., NSCLC or other cancers with RAS pathway activation) with administration via oral gavage or intraperitoneal injection. Tumor growth inhibition and pharmacodynamic effects (p-ERK, DUSP6 mRNA) would be assessed.
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| ADME/Pharmacokinetics |
Pharmacokinetic data are limited. As a small molecule (MW 352.26), it is expected to have reasonable oral bioavailability. Detailed PK parameters (Cmax, AUC, t½) are not extensively reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported. As a research compound, comprehensive toxicological profiling has not been performed.
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| References |
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| Additional Infomation |
This is a research compound, not an approved drug. It is a tool for studying SHP2 biology and evaluating SHP2 inhibition as a cancer therapeutic strategy. CAS number: 1957276-35-5. Also known as SHP-836. It is a novel selective allosteric SHP2 inhibitor.
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| Molecular Formula |
C16H19CL2N5
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|---|---|
| Molecular Weight |
352.261560678482
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| Exact Mass |
351.101
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| CAS # |
1957276-35-5
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| PubChem CID |
76966642
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| Appearance |
Light green to green solid powder
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
23
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| Complexity |
389
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| Defined Atom Stereocenter Count |
2
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| SMILES |
ClC1C(=CC=CC=1C1C=NC(=NC=1N)N1C[C@@H](C)N[C@@H](C)C1)Cl
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| InChi Key |
SKFRRNOLFFQBQU-AOOOYVTPSA-N
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| InChi Code |
InChI=1S/C16H19Cl2N5/c1-9-7-23(8-10(2)21-9)16-20-6-12(15(19)22-16)11-4-3-5-13(17)14(11)18/h3-6,9-10,21H,7-8H2,1-2H3,(H2,19,20,22)/t9-,10+
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| Chemical Name |
5-(2,3-dichlorophenyl)-2-[(3S,5R)-3,5-dimethylpiperazin-1-yl]pyrimidin-4-amine
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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 |
| 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 : ~250 mg/mL (~709.70 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (17.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 6.25 mg/mL (17.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 6.25 mg/mL (17.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8388 mL | 14.1941 mL | 28.3881 mL | |
| 5 mM | 0.5678 mL | 2.8388 mL | 5.6776 mL | |
| 10 mM | 0.2839 mL | 1.4194 mL | 2.8388 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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