| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg | |||
| Other Sizes |
| Targets |
SHP2 (PTPN11). SHP836 HCl allosterically inhibits SHP2, binding to a specific cleft distinct from the catalytic active site. This binding stabilizes the auto-inhibitory conformation of the enzyme, preventing its activation by growth factors or cytokines. This allosteric mechanism offers high selectivity over other phosphatases. Inhibition of SHP2 blocks downstream signaling pathways, primarily the RAS-ERK pathway, which is crucial for cell proliferation, differentiation, and survival. The IC₅0 for full-length SHP2 is 12 microM.
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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 HCl inhibits recombinant human SHP2 in non-cellular biochemical assays. The allosteric mechanism has been validated through surface plasmon resonance (SPR), confirming direct binding to the allosteric pocket. In cellular assays, treatment with the compound downregulates the expression of DUSP6 mRNA, a known transcriptional target and negative-feedback regulator of ERK signaling, confirming functional target engagement. This leads to decreased phosphorylation of ERK1/2 (p-ERK), a direct downstream effector of the RAS pathway. |
| ln Vivo |
Specific in vivo efficacy data for SHP836 HCl in animal models has not been extensively published in the search results. However, as an inhibitor of SHP2, it is expected to suppress tumor growth in xenograft mouse models of cancers driven by the RAS-ERK pathway (e.g., certain lung cancers, leukemias). A typical study would involve oral administration of the compound (due to its drug-like properties) to mice bearing patient-derived tumors, measuring tumor volume reduction and confirming p-ERK suppression in harvested tumor tissue by Western blot.
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| Enzyme Assay |
A non-radioactive phosphatase assay is performed. Purified recombinant full-length SHP2 protein is incubated with a surrogate phosphorylated tyrosine peptide substrate (e.g., DiFMUP or pNPP) in reaction buffer. Varying concentrations of SHP836 HCl are added, and the reaction is started by adding the substrate. Dephosphorylation is allowed to proceed for 30-60 minutes at room temperature. The reaction is terminated by the addition of NaOH, and the fluorescence (Ex: 360 nm, Em: 450 nm for DiFMUP) is measured to determine the IC₅0.
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| Cell Assay |
To assess cellular activity, cancer cell lines (e.g., KYSE-520 esophageal, NCI-H661 lung) are seeded in 6-well plates and treated with SHP836 HCl (0-50 microM) for 24-48 hours. Cells are then lysed, and protein concentration is normalized. Lysates are analyzed by Western blotting for total ERK1/2 and phosphorylated ERK1/2 (p-ERK) to assess pathway inhibition. Additionally, quantitative PCR (qRT-PCR) is performed to measure DUSP6 mRNA expression levels. Cell viability is assessed via CellTiter-Glo or MTT assay to calculate the GI₅0.
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| Animal Protocol |
A standard xenograft model is used. Female athymic nude mice are inoculated subcutaneously with 5 × 10⁶ cancer cells (e.g., NCI-H661) in Matrigel. When tumors reach ~150 mm3, mice are randomized and administered SHP836 HCl (e.g., 25, 50, or 100 mg/kg) or vehicle by oral gavage daily for 3-4 weeks. Tumor volumes are measured with calipers every 3 days. At the end of the study, tumors are excised, weighed, and analyzed for p-ERK levels and proliferative markers (Ki-67).
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| ADME/Pharmacokinetics |
Specific PK data for SHP836 HCl is not publicly detailed. As a drug-like allosteric inhibitor, it is expected to have suitable properties for oral administration, including moderate molecular weight (352.26) and good solubility in DMSO. General properties for SHP2 inhibitors include a moderate half-life (t1/2) to allow for daily dosing. The compound is soluble in DMSO (> 250 mg/mL) and has a stable solid powder form. It is formulated for in vivo use in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% saline.
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| Toxicity/Toxicokinetics |
Specific toxicity data for SHP836 HCl has not been reported in the search results. Given that SHP2 is a widely expressed phosphatase, systemic inhibition could potentially lead to non-specific organ toxicity or impair normal cell signaling in healthy tissues. However, clinical experience with other SHP2 inhibitors suggests that toxicities may be manageable. Standard handling precautions, such as avoiding inhalation and skin contact, are required. In vitro cell viability assays provide a preliminary assessment of cytotoxic potential.
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| References |
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| Additional Infomation |
SHP836 HCl is a research-grade compound, not a clinical drug, and has not received approval for human use. It is classified as a selective allosteric SHP2 inhibitor with anticancer activity. It can be synthesized with high purity (≥98%) and is available for chemical biology studies. This compound is particularly useful for probing the role of SHP2 in growth factor, cytokine, and oncogenic signaling in cancer research.
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| Molecular Formula |
C16H19CL2N5
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|---|---|
| Molecular Weight |
352.261560678482
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| Exact Mass |
351.102
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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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| 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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| 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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