| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
IC50: 70 nM (SHP2)[1]
SHP2 (PTPN11). SHP099 is an allosteric SHP2 inhibitor that binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, stabilizing the autoinhibited conformation and preventing SHP2 activation. |
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| ln Vitro |
SHP099's X-ray co-crystal with SHP2 demonstrates a novel interaction between the basic amine and the carbonyl of the Phe113 backbone. SHP099 exhibits a 1.4 μM IC50 in the KYSE-520 model, which inhibits cell proliferation. In Caco-2 cells, SHP099 exhibits great permeability and solubility with no discernible efflux[1]. Through an allosteric mechanism, SHP099 inhibits SHP2 activity by concurrently binding to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains. SHP099 prevents receptor-tyrosine-kinase-driven human cancer cells from proliferating by suppressing RAS-ERK signaling[2].
SHP099 monohydrochloride inhibits SHP2 with an IC50 of 70 nM in biochemical assays. It is a potent, selective, and orally bioavailable SHP2 inhibitor. In cellular assays, SHP099 inhibits RAS-MAPK signaling, reduces pERK levels, and suppresses cell proliferation in cancer cell lines with activated SHP2 or receptor tyrosine kinase (RTK) mutations. |
| ln Vivo |
The xenografts exhibit dose-dependent exposure and modification of the pharmacodynamic marker p-ERK following single doses of 30 and 100 mg/kg. An oral dosage of 10 mg/kg or 30 mg/kg per day inhibits tumor growth by 19% and 61%, respectively. 100 mg/kg is the threshold for tumor stasis [1].
SHP099 monohydrochloride is used in biochemical and cellular studies to probe SHP2-dependent signaling pathways. It has shown antitumor activity in mouse xenograft models of cancers driven by SHP2 activation, including RTK-mutant and RAS pathway-driven tumors. Oral administration reduces tumor growth and pERK levels in tumor tissue. SHP099 has been instrumental in validating SHP2 as a therapeutic target. |
| Enzyme Assay |
Cell-free SHP2 phosphatase activity assays are performed using recombinant SHP2 enzyme and a bis-phosphorylated IRS-1 peptide substrate. The reaction is carried out in 96-well plates in assay buffer (50 mM HEPES, pH 7.2, 100 mM NaCl, 5 mM DTT, 2 mM EDTA) with increasing concentrations of SHP099 (0.01-10,000 nM). After 30-60 min at 25degC, the reaction is terminated, and released phosphate is quantified using a malachite green phosphate detection kit or by measuring fluorescence of a fluorescently labeled substrate. IC50 is determined by nonlinear regression.
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| Cell Assay |
Human cancer cell lines with SHP2-dependent signaling (e.g., KYSE520 esophageal cancer, NCI-H441 lung cancer) are seeded and treated with SHP099 (0.1-10 uM) for 24-72 hours. Cell viability is assessed by MTT or CellTiter-Glo assay. pERK levels (downstream of RAS-MAPK) are measured by Western blot or phospho-flow cytometry. Apoptosis is measured by Annexin V/PI staining. Colony formation assays are performed over 7-14 days. IC50 values for growth inhibition are determined.
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| Animal Protocol |
SHP099 is administered orally to mice (10-100 mg/kg, once or twice daily) in tumor xenograft models (e.g., KYSE520, NCI-H441). Tumor volumes are measured with calipers every 2-3 days. Body weight is monitored. At study termination, tumors are excised for pERK measurement by Western blot or immunohistochemistry. Pharmacodynamic studies: blood and tumor samples are collected at various time points after dosing to assess SHP2 target engagement and pathway inhibition. SHP099 is formulated in 0.5% methylcellulose for oral gavage.
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| ADME/Pharmacokinetics |
PK: SHP099 is orally bioavailable. It is a potent, selective, and orally available SHP2 inhibitor with an IC50 of 70 nM. PK parameters: molecular weight 388.72 (C16H20Cl3N5). Solubility: DMSO 78 mg/mL (200.66 mM), water 6 mg/mL (15.44 mM), ethanol insoluble. Storage: -20degC. Detailed PK parameters (t1/2, Cmax, AUC, oral bioavailability) in rodents have been characterized but are not fully reported in the literature. The compound exhibits favorable PK properties for in vivo studies.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for SHP099 monohydrochloride. In published in vivo studies at doses up to 100 mg/kg orally, no overt signs of toxicity (significant weight loss, behavioral changes, or mortality) were observed. As an allosteric SHP2 inhibitor, its safety profile is expected to be favorable, but comprehensive toxicological assessments (hERG, Ames, repeat-dose toxicity in rats/dogs) have not been published. No FDA approval.
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| References |
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| Additional Infomation |
Other information: SHP099 monohydrochloride (CAS 2200214-93-1) is a research compound, not FDA-approved. It is a potent, selective, and orally bioavailable allosteric SHP2 inhibitor with an IC50 of 70 nM. It is used as a chemical probe to study SHP2-dependent signaling pathways in cancer and other diseases. The monohydrochloride salt is the hydrochloride salt of SHP099. Purity ≥98%. For research use only. Synonyms: SHP099 HCl, SHP099 hydrochloride.
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| Molecular Formula |
C16H20CL3N5
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|---|---|
| Molecular Weight |
388.7225
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| Exact Mass |
387.078
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| CAS # |
2200214-93-1
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| Related CAS # |
SHP099;1801747-42-1;SHP099 hydrochloride;1801747-11-4
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| PubChem CID |
121241170
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| Appearance |
Yellow to orange solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
24
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| Complexity |
402
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C(=C([H])C([H])=C([H])C=1C1C(N([H])[H])=NC(=C([H])N=1)N1C([H])([H])C([H])([H])C(C([H])([H])[H])(C([H])([H])C1([H])[H])N([H])[H])Cl.Cl[H]
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| InChi Key |
KHQHYRFUYAXWOQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H19Cl2N5.ClH/c1-16(20)5-7-23(8-6-16)12-9-21-14(15(19)22-12)10-3-2-4-11(17)13(10)18;/h2-4,9H,5-8,20H2,1H3,(H2,19,22);1H
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| Chemical Name |
6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3-dichlorophenyl)pyrazin-2-amine;hydrochloride
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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: 4.1 mg/mL (10.55 mM)
H2O: ≥ 2.5 mg/mL (6.43 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.43 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 25.0 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: 20 mg/mL (51.45 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5725 mL | 12.8627 mL | 25.7255 mL | |
| 5 mM | 0.5145 mL | 2.5725 mL | 5.1451 mL | |
| 10 mM | 0.2573 mL | 1.2863 mL | 2.5725 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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