SHP099 |
Catalog No.GC44887
One-Click Copy Product Info
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SHP099 is a highly potent, selective, orally bioavailable SHP2 inhibitor, with an IC50 value of 0.071μM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1801747-42-1
Sample solution is provided at 25 µL, 10mM.
SHP099 is a highly potent, selective, orally bioavailable SHP2 inhibitor, with an IC50 value of 0.071μM [1]. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism [2]. SHP099, widely used to inhibit the in vitro proliferation of various cancer cells, has been employed as an anti-cancer agent in mouse tumor xenograft models[3].
In vitro, SHP099 significantly inhibited the proliferation of PC9 cells and PC9GR cells within 24 hours, with IC50 values of 7.536 and 8.900μM, respectively[4]. Treatment with 20μM SHP099 for one week significantly inhibited the phosphorylation of ERK protein in synovial mesenchymal stem cells (SMSCs), promoted the expression of SOX9 and COL2, and reduced the expression of the COL10 without affecting cell viability[5]. Treatment with 5µM SHP099 for 3 days significantly promoted the accumulation of proteins related to induced cell death (including cleaved caspase-3) in human umbilical vein endothelial cells (HUEVCs), and reduced the decrease of pro-survival proteins (including Survivin), significantly inducing cell death[6].
In vivo, SHP099 treatment via intraperitoneal injection at 5mg/kg/day for 17 days inhibited the tumor growth of CT-26 cell xenograft BALB/c mice, without affecting body weight of mice[7]. A single intraperitoneal injection of 15mg/kg of SHP099 for 12 hours significantly inhibited the pulmonary inflammatory response in the acute lung injury mouse model and increased the survival rate of the mice[8].
References:
[1] Wu J, Zhang H, Zhao G, et al. Allosteric inhibitors of SHP2: an updated patent review (2015-2020)[J]. Current Medicinal Chemistry, 2021, 28(19): 3825-3842.
[2] Wang M, Li T, Ouyang Z, et al. SHP2 allosteric inhibitor TK-453 alleviates psoriasis-like skin inflammation in mice via inhibition of IL-23/Th17 axis[J]. Iscience, 2022, 25(4).
[3] Sang Y, Hou Y, Cheng R, et al. Targeting PDGFRα-activated glioblastoma through specific inhibition of SHP-2–mediated signaling[J]. Neuro-oncology, 2019, 21(11): 1423-1435.
[4] Xia L, Yang F, Wu X, et al. SHP2 inhibition enhances the anticancer effect of Osimertinib in EGFR T790M mutant lung adenocarcinoma by blocking CXCL8 loop mediated stemness[J]. Cancer Cell International, 2021, 21(1): 337.
[5] Sun Z, Xu X, Lv Z, et al. Intraarticular injection of SHP2 inhibitor SHP099 promotes the repair of rabbit full-thickness cartilage defect[J]. Journal of Orthopaedic Translation, 2022, 32: 112-120.
[6] Wang Y, Salvucci O, Ohnuki H, et al. Targeting the SHP2 phosphatase promotes vascular damage and inhibition of tumor growth[J]. EMBO Molecular Medicine, 2021, 13(7): e14089.
[7] Zhao M, Guo W, Wu Y, et al. SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade[J]. Acta Pharmaceutica Sinica B, 2019, 9(2): 304-315.
[8] Ye S, Zuo B, Xu L, et al. Inhibition of SHP2 by the small molecule drug SHP099 prevents lipopolysaccharide-induced acute lung injury in mice[J]. Inflammation, 2023, 46(3): 975-986.
| Cell experiment [1]: | |
Cell lines | PC9 cells |
Preparation Method | The PC9 cells were all cultured in Dulbecco’s Modified Eagle Medium (DMEM) containing 10% fetal bovine serum (FBS), 100U/mL penicillin and 100mg/mL streptomycin. The cells were cultured at 37℃ and 5% CO2. 2×103 cells were inoculated into each well of a 96-well plate, and 200µL of the medium was added to each well. The cells were incubated with different concentrations of SHP099 (0, 0.625, 1.25, 2.5, 5, 10, and 20μM) for 24h. 50µL of MTT solution was added to the bottom of each well, and the cells were incubated for 4 hours. The absorbance was measured at 490nm using a microplate reader. |
Reaction Conditions | 0, 0.625, 1.25, 2.5, 5, 10, and 20μM; 24h |
Applications | SHP099 significantly inhibited the viability of PC9 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Female BALB/c mice |
Preparation Method | Female BALB/c mice (6-8 weeks old) were housed in a specific pathogen-free (SPF) facility with a 12-hour daily cycle, and had free access to food and water. CT-26 cells were inoculated subcutaneously into BALB/c mice (1×106). The tumor size was measured every day after inoculation, and tumor size was calculated as 0.5×length×width2. Mice with similar tumor sizes were randomly divided into 5 groups and received PBS, 5-Fu, or SHP099. SHP099 was administered intraperitoneally at 5mg/kg daily, and anti-PD-1 antibody was administered intraperitoneally at 5mg/kg every 3 days. After 17 days, the mice were sacrificed and the tumor tissues were collected for analysis. |
Dosage form | 5mg/kg/day for 17 days; i.p. |
Applications | SHP099 treatment inhibited the tumor growth of CT-26 cell xenograft BALB/c mice, and caused the shrinking, sparse arrangement and fragmentation of tumor cells. |
References: | |
| Cas No. | 1801747-42-1 | SDF | |
| Canonical SMILES | ClC1=C(Cl)C(C2=NC=C(N3CCC(C)(N)CC3)N=C2N)=CC=C1 | ||
| Formula | C16H19Cl2N5 | M.Wt | 352.3 |
| Solubility | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS(pH 7.2) (1:2): 0.33 mg/ml,Ethanol: 10 mg/ml | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.8385 mL | 14.1924 mL | 28.3849 mL |
| 5 mM | 567.7 μL | 2.8385 mL | 5.677 mL |
| 10 mM | 283.8 μL | 1.4192 mL | 2.8385 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 23 reference(s) in Google Scholar.)