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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
SHP099 HCl, the HCl salt of SHP-099, is an orally bioavailable, and allosteric SHP2 inhibitor with antitumor and anti-inflammatory effects. The inhibitor has an IC50 of 70 nM and inhibits SHP2 [Src homology-2 domain containing protein tyrosine phosphatase-2]. The PTPN11 gene encodes SHP2, a nonreceptor protein tyrosine phosphatase (PTP) that is involved in cell growth and differentiation through the MAPK signaling pathway. Additionally, SHP2 is said to be crucial to the PD-1/PD-L1 pathway, which causes programmed cell death. SHP099 functions as an allosteric modulator (inhibitor) of SHP2, stabilizing the autoinhibited conformation. The binding location in a previously unidentified allosteric binding pocket was identified by X-ray crystallography.
| Targets |
SHP-2 (IC50 = 0.07 μM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
Biochemical assay. The binding of bis-tyrosylphorphorylated peptides to SHP2's Src Homology 2 (SH2) domains causes allosteric activation of the protein. The release of SHP2's auto-inhibitory interface during the latter activation step makes the SHP2 PTP active and ready for substrate recognition and reaction catalysis. The surrogate substrate DiFMUP was used in a prompt fluorescence assay format to track the catalytic activity of SHP2. Phosphatase reactions were carried out in a 384-well black polystyrene plate with a flat bottom, low flange, and non-binding surface (Corning, Cat# 3575) at room temperature. A final reaction volume of 25 μL was used, and the assay buffer conditions were as follows: pH 7.2, 75 mM NaCl, 75 mM KCl, 1 mM EDTA, 0.05% P-20, and 5 mM DTT are all present in 60 mM HEPES. Using an assay where 0.5 nM of SHP2 was incubated with 0.5 μM of peptide IRS1_pY1172(dPEG8)pY1222 (sequence:H2NLN(pY)IDLDLV(dPEG8)LST(pY)ASINFQK-amide), the inhibitory effect of the tested compounds (concentrations ranging from 0.003 – 100 μM) was observed. The reaction was incubated at 25 oC for 30 minutes (200 μM for 2-593, 100 μM for 1-525 construct) after the surrogate substrate DiFMUP (Invitrogen, cat# D6567, 200 μM) was added. The next step involved adding 5 μL of a 160 μM bpV(Phen) solution (Enzo Life Sciences cat# ALX-270-204) to quench the reaction. At excitation and emission wavelengths of 340 nm and 450 nm, respectively, the fluorescence signal was observed using a microplate reader (Envision, Perki-Elmer). Normalized IC50 regression curve fitting with control-based normalization was used to analyze the inhibitor dose response curves.
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| Cell Assay |
In a 96-well plate culture, KYSE-520 cells (30,000 cells/well) are grown overnight and then treated with SHP2 inhibitors for two hours at 37 °C at concentrations of 20, 6.6, 2.2, 0.74, 0.24, 0.08, and 0.027 μM. 30 μL of the lysis buffer included with the SureFire p-ERK assay kit is added to end the incubations.
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| Animal Protocol |
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| References |
| Molecular Formula |
C16H19CL2N5.HCL
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| Molecular Weight |
388.72
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| Exact Mass |
351.10
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| Elemental Analysis |
C, 49.44; H, 5.19; Cl, 27.36; N, 18.02
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| CAS # |
1801747-11-4
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| Related CAS # |
SHP099;1801747-42-1;SHP099 monohydrochloride;2200214-93-1
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| Appearance |
Yellow solid powder
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| SMILES |
CC1(CCN(CC1)C2=CN=C(C(=N2)N)C3=C(C(=CC=C3)Cl)Cl)N.Cl
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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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| Synonyms |
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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 |
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| 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) |
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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 | 2.5725 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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