Adezmapimod (SB203580)

Catalog No.S1076 Batch:S107616

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Technical Data

Formula

C21H16FN3OS

Molecular Weight 377.43 CAS No. 152121-47-6
Solubility (25°C)* In vitro DMSO 38 mg/mL (100.68 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
4%DMSO 30%PEG300 5%Tween80 61%ddH2O
5.0mg/ml Taking the 1 mL working solution as an example, add 40 μL of 125 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 610 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Adezmapimod (SB203580, RWJ 64809, PB 203580) is a p38 MAPK inhibitor with IC50 of 0.3-0.5 μM in THP-1 cells, 10-fold less sensitive to SAPK3(106T) and SAPK4(106T) and blocks PKB phosphorylation with IC50 of 3-5 μM. SB203580 induces mitophagy and autophagy.
Targets
p38 MAPK [1]
(THP-1 cells)
PKB [1]
(THP-1 cells)
0.3 μM-0.5 μM 3 μM-5 μM
In vitro SB203580 inhibits the IL-2-induced proliferation of primary human T cells, murine CT6 T cells, or BAF F7 B cells with an IC50 of 3–5 μm. SB203580 also inhibits IL-2-induced p70S6 kinase activation, although the concentration required is slightly higher with an IC50 above 10 μm. SB203580 also inhibits the activity of PDK1 in a dose-dependent manner with an IC50 in the 3–10 μm range. [1] SB203580 inhibits p38-MAPK stimulation of MAPKAPK2 with an IC50 of approximately 0.07 μM, whereas inhibits total SAPK/JNK activity with an IC50 of 3–10 μM. SB203580 at higher concentrations activates the ERK pathway, which subsequently enhances NF-κB transcriptional activity. [2] SB203580 induces autophagy in human hepatocellular carcinoma (HCC) cells. [3]
In vivo SB203580 protects pig myocardium against ischemic injury in an in vivo model. [4]SB203580 is effective to prevent and treat the disease in MRL/lpr mice model of Systemic lupus erythematosus (SLE). [5]
Features First reported p38 inhibitor.

Protocol (from reference)

Kinase Assay:

[1]

  • Cellular receptor kinase phosphorylation assay

    4 μg of sheep anti-PKBα is immobilized on 25 μL of protein G-Sepharose overnight (or 1.5 hours) and washed in Buffer A (50 mm Tris, pH 7.5, 1 mm EDTA, 1 mm EGTA, 0.5 mm Na3VO4, 0.1% β-mercaptoethanol, 1% Triton X-100, 50 mm sodium fluoride, 5 mm sodium pyrophosphate, 0.1 mm phenylmethylsulfonyl fluoride, 1 μg/mL aprotinin, pepstatin, leupeptin, and 1 μm microcystin). The immobilized anti-PKB is then incubated with 0.5 ml of lysate (from 5 × 106 cells) for 1.5 hours and washed three times in 0.5 mL of Buffer A supplemented with 0.5 m NaCl, two times in 0.5 mL of Buffer B (50 mm Tris-HCl, pH 7.5, 0.03% (w/v) Brij-35, 0.1 mm EGTA, and 0.1% β-mercaptoethanol), and twice with 100 μl of assay dilution buffer; 5× assay dilution buffer is 100 mm MOPS, pH 7.2, 125 mm β-glycerophosphate, 25 mm EGTA, 5 mm sodium orthovanadate, 5 mm DTT. To the PKB enzyme immune complex is added 10 μL of assay dilution buffer, 40 μm protein kinase A inhibitor peptide, 100 μm PKB-specific substrate peptide, and 10 μCi of [γ-32P]ATP, all made up in assay dilution buffer. The reaction is incubated for 20 minutes at room temperature with shaking, then samples are pulse spun, and 40 μL of reaction volume are removed into another tube to which is added 20 μL of 40% trichloroacetic acid to stop the reaction. This is mixed and incubated for 5 minutes at room temperature, and 40 μL is transferred onto P81 phosphocellulose paper and allowed to bind for 30 seconds. The P81 piece is washed three times in 0.75% phosphoric acid then in acetone at room temperature. γ-32P incorporation is then measured by scintillation counting.

Cell Assay:

[1]

  • Cell lines

    CT6 cell , BA/F3 F7 cell

  • Concentrations

    0–30 μM

  • Incubation Time

    1 hour

  • Method

    CT6 cell and BA/F3 F7 cell are rested by washing three times in RPMI and culturing overnight in RPMI, 5% fetal calf serum in the absence of growth factor, antibiotics, or β-mercaptoethanol supplements. 2–5 × 106 rested CT6 cells are resuspended in 2 mL of RPMI, 5% fetal calf serum and preincubated with SB203580 or vehicle control as indicated in figure legends. Cells are then stimulated with 20 ng/ml recombinant human IL-2 for 5 minutes at 37  °C and pelleted in a minifuge for 30 seconds, medium is aspirated, and the pellet is lysed in the appropriate buffer. BA/F3 cells stably expressing deletion mutants of IL-2 receptor β chain are maintained in glutamine containing RPMI further supplemented with 5% fetal calf serum and 0.2 μg/mL G418. The cells are then washed extensively, rested overnight, and washed again before activating with IL-2; such cell preparations are >90% T cells. Cellular proliferation assays are performed by measurement of [3H]thymidine incorporation.

Animal Study:

[5]

  • Animal Models

    Systemic lupus erythematosus (SLE) are established in female MRL/lpr mice and female C57BL/6 mice

  • Dosages

    0.1 M/day

  • Administration

    Orally administered

Customer Product Validation

Data from [J Biol Chem, 2010, 285, 32824-32833]

Data from [J Biol Chem, 2010, 285, 32824–32833]

Data from [J Biol Chem, 2010, 285, 32824–32833]

Data from [Data independently produced by , , Science, 2018, 11(525), doi: 10.1126/scisignal.aao3428]

Selleck's Adezmapimod (SB203580) has been cited by 936 publications

Phosphorylation of human glioma-associated oncogene 1 on Ser937 regulates Sonic Hedgehog signaling in medulloblastoma [ Nat Commun, 2024, 15(1):987] PubMed: 38307877
Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src [ Nat Commun, 2024, 15(1):1300] PubMed: 38346942
Bactericidal/permeability-increasing protein instructs dendritic cells to elicit Th22 cell response [ Cell Rep, 2024, 43(3):113929] PubMed: 38457343
Ammonia stress-induced heat shock factor 1 enhances white spot syndrome virus infection by targeting the interferon-like system in shrimp [ mBio, 2024, e0313623.] PubMed: 38358252
Securinine inhibits the tumor growth of human bladder cancer cells by suppressing Wnt/β-catenin signaling pathway and activating p38 and JNK signaling pathways [ Biochem Pharmacol, 2024, 223:116125] PubMed: 38484850
ERK1/2-CEBPB Axis-Regulated hBD1 Enhances Anti-Tuberculosis Capacity in Alveolar Type II Epithelial Cells [ Int J Mol Sci, 2024, 25(4)2408] PubMed: 38397085
PCSK9 increases vulnerability of carotid plaque by promoting mitochondrial dysfunction and apoptosis of vascular smooth muscle cells [ CNS Neurosci Ther, 2024, 30(2):e14640] PubMed: 38402551
FGF18 alleviates sepsis-induced acute lung injury by inhibiting the NF-κB pathway [ Respir Res, 2024, 25(1):108] PubMed: 38419044
Licochalcone A induces mitochondria-dependent apoptosis and interacts with venetoclax in acute myeloid leukemia [ Eur J Pharmacol, 2024, 968:176418] PubMed: 38350590
Antioxidant and Antimelanogenic Activities of Lactobacillus kunkeei NCHBL-003 Isolated from Honeybees [ Microorganisms, 2024, 12(1)188] PubMed: 38258014

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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