| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| 10mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
SHP394 targets SHP2 (protein tyrosine phosphatase non-receptor type 11), a phosphatase that mediates signaling downstream of receptor tyrosine kinases, including the RAS-MAPK pathway. SHP2 is an oncogenic driver and a resistance mechanism to targeted kinase inhibitors. SHP394 acts as a selective allosteric inhibitor, binding to an allosteric site on SHP2 to lock it in an auto-inhibited conformation.
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| ln Vitro |
SHP394 has an IC50 of 297 nM, which suppresses the growth of Caco-2 cells[1]. In vitro, SHP394 has anti-proliferative action (IC50= 1.38 μM) against the Detroit-562 pharyngeal cancer cell line [1]. In KYSE520 cells, SHP394 lowers p-ERK with an IC50 of 18 nM [1].
SHP394 blocks SHP2-dependent signaling, reducing p-ERK in KYSE520 cells with an IC50 of 18 nM. It inhibits proliferation of Caco-2 colorectal cells (IC50 297 nM) and Detroit-562 pharyngeal carcinoma cells (IC50 1.38 μM). These data demonstrate potent on-target activity and antiproliferative effects in cancer cell lines driven by SHP2 signaling. |
| ln Vivo |
Tumor volume is reduced by SHP394 (20–80 mg/kg; oral gavage; twice daily) in a dose-dependent manner [1]. Within 14 days, SHP394 (80 mg/kg; oral gavage; twice daily) caused a 34% tumor regression and decreased the body weight of the mice [1].
SHP394 shows in vivo efficacy in tumor-bearing mice. Twice-daily oral dosing at 20-80 mg/kg leads to dose-dependent tumor volume reduction, with 80 mg/kg producing approximately 34% regression over 14 days. These results confirm that SHP394 is orally bioavailable and efficacious in vivo, supporting its use as a tool compound for studying SHP2 biology and as a potential therapeutic candidate. |
| Enzyme Assay |
SHP2 inhibition is assessed using biochemical phosphatase assays with purified recombinant SHP2 protein and a synthetic phosphopeptide substrate. The enzymatic activity of SHP2 is measured by monitoring the release of phosphate using a malachite green or coupled enzyme assay. SHP394 is incubated with SHP2 at various concentrations, and IC50 values are calculated from dose-response curves. Selectivity profiling is performed using a panel of related phosphatases (e.g., SHP1, PTP1B) to confirm selectivity.
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| Cell Assay |
Cellular activity is evaluated in KYSE520 esophageal cancer cells (which are SHP2-dependent). Cells are treated with SHP394 at various concentrations, and p-ERK levels are measured by Western blot or phospho-specific ELISA to assess inhibition of SHP2-dependent signaling. Antiproliferative effects are assessed in Caco-2 colorectal and Detroit-562 pharyngeal carcinoma cells using cell viability assays such as MTT or CellTiter-Glo after 72-96 hours of treatment. IC50 values for proliferation inhibition are calculated.
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| Animal Protocol |
Animal/Disease Models: Sixweeks old female athymic NU/nu (nude) mice were subcutaneously (sc) (sc) inoculated with Detroit-562 pharyngeal cancer cells [1].
Doses: 20, 40 and 80 mg/kg Route of Administration: po (oral gavage); twice (two times) daily Experimental Results: Demonstrated significant dose-dependent reduction in tumor volume. SHP394 is administered orally to tumor-bearing mice at doses of 20, 40, and 80 mg/kg twice daily. Tumor volumes are measured twice weekly using calipers, and body weight is monitored for tolerability. Treatment typically continues for 14 days or until tumors reach a predefined endpoint. Tumor growth inhibition (TGI) and regression are calculated relative to vehicle controls. Pharmacodynamic studies may include measurement of p-ERK levels in tumor tissue to confirm target engagement. |
| ADME/Pharmacokinetics |
SHP394 has a molecular weight of 470.51 and molecular formula C20H25F3N6O2S. It is an orally active compound suitable for oral dosing in preclinical studies. Powder formulations are stable at -20°C for up to 3 years, and in solvent at -80°C for 1 year. Shipping is typically performed with blue ice or at ambient temperature. The compound is soluble in DMSO. SHP394 is a selective allosteric SHP2 inhibitor.
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| Toxicity/Toxicokinetics |
SHP394 is an orally active, selective allosteric inhibitor of SHP2 with an IC50 of 23 nM. It is useful for interrogating SHP2-driven oncogenic pathways and resistance mechanisms to targeted kinase inhibitors. SHP394 represents a valuable tool for studying SHP2 biology and validating SHP2 as a therapeutic target in cancer. The compound is for research use only.
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| References | |
| Additional Infomation |
Preclinical toxicity studies of SHP394 have not been extensively reported in the literature. However, as a potent SHP2 inhibitor, the primary mechanism-based toxicities may include effects on hematopoietic cell development and immune function, given the role of SHP2 in cytokine signaling. Body weight monitoring in tumor-bearing mice at doses up to 80 mg/kg twice daily suggests that the compound is tolerated at efficacious doses. Further toxicological characterization is required for clinical development.
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| Molecular Formula |
C20H25F3N6O2S
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|---|---|
| Molecular Weight |
470.511712789536
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| Exact Mass |
470.171
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| CAS # |
2055757-40-7
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| PubChem CID |
124150499
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| Appearance |
White to off-white solid powder
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| LogP |
0.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
32
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| Complexity |
812
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| Defined Atom Stereocenter Count |
2
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| SMILES |
S(C1=CC=CN=C1C(F)(F)F)C1=C(N)N=C(N(C)C1=O)N1CCC2(CO[C@@H](C)[C@H]2N)CC1
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| InChi Key |
QZHZIDHAIVAHMD-SMDDNHRTSA-N
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| InChi Code |
InChI=1S/C20H25F3N6O2S/c1-11-14(24)19(10-31-11)5-8-29(9-6-19)18-27-16(25)13(17(30)28(18)2)32-12-4-3-7-26-15(12)20(21,22)23/h3-4,7,11,14H,5-6,8-10,24-25H2,1-2H3/t11-,14+/m0/s1
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| Chemical Name |
6-amino-2-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-3-methyl-5-((2-(trifluoromethyl)pyridin-3-yl)thio)pyrimidin-4(3H)-one
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| Synonyms |
SHP394 SHP-394 SHP 394
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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 (e.g. under nitrogen), 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 : ~24 mg/mL (~51.01 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (13.28 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 (13.28 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 (13.28 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 | 2.1254 mL | 10.6268 mL | 21.2535 mL | |
| 5 mM | 0.4251 mL | 2.1254 mL | 4.2507 mL | |
| 10 mM | 0.2125 mL | 1.0627 mL | 2.1254 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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