IF 13
PMID: 34569725 ↗SHP099
Catalog No.: GC44887Purity:>99.50%
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
10mM (in 1mL DMSO)In Stock
$62.00
1
5mgIn Stock
$56.00
1
10mgIn Stock
$102.00
1
25mgIn Stock
$165.00
1
50mgIn Stock
$251.00
1
100mgIn Stock
$350.00
1
| Pack Size | Price | Availability | Quantity | Action |
|---|---|---|---|---|
| 10mM (in 1mL DMSO) | $62.00 | In Stock | 1 | |
| 5mg | $56.00 | In Stock | 1 | |
| 10mg | $102.00 | In Stock | 1 | |
| 25mg | $165.00 | In Stock | 1 | |
| 50mg | $251.00 | In Stock | 1 | |
| 100mg | $350.00 | In Stock | 1 |
Tel: (909) 407-4943 / (909) 689-7124Email: sales@glpbio.com
Citations
1 publicationsPublications from researchers using this productDescription
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.
Protocol
| 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: | |
Product Documents
Purity:>99.50%Appearance:A solid
Chemical Properties
CAS No.
1801747-42-1
SMILES
ClC1=C(Cl)C(C2=NC=C(N3CCC(C)(N)CC3)N=C2N)=CC=C1
Molecular Formula
C16H19Cl2N5
Molecular Weight
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
Select a suitable solvent according to the product solubility data. Once prepared, aliquot the stock solution to avoid repeated freeze-thaw cycles.
Use stock solutions within 6 months when stored at -80°C or within 1 month when stored at -20°C.
To improve solubility, warm the tube to 37°C and sonicate it for an appropriate period.
Use stock solutions within 6 months when stored at -80°C or within 1 month when stored at -20°C.
To improve solubility, warm the tube to 37°C and sonicate it for an appropriate period.
Shipping Condition
Evaluation samples are shipped with blue ice. Other available sizes are shipped at room temperature or with blue ice upon request.
CalculatorsMolarity / Dilution / Molecular Weight / Unit Conversion / In Vivo Formulation / Solubility
g/mol
Reviews
Review for SHP099
Rating: 5
- 5 Star100%
- 4 Star0%
- 3 Star0%
- 2 Star0%
- 1 Star0%