Adezmapimod (SB203580)

製品コードS1076 バッチS107613

印刷

化学情報

Chemical Structure Synonyms RWJ 64809, PB 203580 Storage
(From the date of receipt)		 3 years-20°C （in the dark）powder
化学式

C21H16FN3OS
分子量 377.43 CAS No. 152121-47-6
Solubility (25°C)* 体外 DMSO (warmed with 50ºC water bath) 59 mg/mL (156.32 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
in vitro

Adezmapimod (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. It also inhibits IL-2-induced p70S6 kinase activation, although the concentration required is slightly higher with an IC50 above 10 μm. This compound inhibits the activity of PDK1 in a dose-dependent manner with an IC50 in the 3–10 μm range. [1] It inhibits p38-MAPK stimulation of MAPKAPK2 with an IC50 of approximately 0.07 μM, whereas it inhibits total SAPK/JNK activity with an IC50 of 3–10 μM. At higher concentrations, it activates the ERK pathway, which subsequently enhances NF-κB transcriptional activity. [2] It also induces autophagy in human hepatocellular carcinoma (HCC) cells. [3]
in vivo

Adezmapimod (SB203580) protects pig myocardium against ischemic injury in an in vivo model. [4]It is effective to prevent and treat the disease in MRL/lpr mice model of Systemic lupus erythematosus (SLE). [5]
特徴 First reported p38 inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ 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 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.
細胞アッセイ 細胞株 CT6 cell , BA/F3 F7 cell
濃度 0–30 μM
反応時間 1 hour
実験の流れ

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 Adezmapimod (SB203580) or vehicle control as indicated in figure legends. It is then used in subsequent steps where cells are 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.
動物実験 動物モデル Systemic lupus erythematosus (SLE) are established in female MRL/lpr mice and female C57BL/6 mice
投薬量 0.1 M/day
投与方法 Orally administered

参考

  • https://pubmed.ncbi.nlm.nih.gov/10702313/
  • https://pubmed.ncbi.nlm.nih.gov/10960075/
  • https://pubmed.ncbi.nlm.nih.gov/22170404/
  • https://pubmed.ncbi.nlm.nih.gov/10710135/
  • https://pubmed.ncbi.nlm.nih.gov/21549858/

カスタマーフィードバック

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]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Oncogenic RAS induces a distinctive form of non-canonical autophagy mediated by the P38-ULK1-PI4KB axis [ Cell Res, 2025, 10.1038/s41422-025-01085-9] PubMed: 40055523
The intrinsic expression of NLRP3 in Th17 cells promotes their protumor activity and conversion into Tregs [ Cell Mol Immunol, 2025, 22(5):541-556] PubMed: 40195474
First-in-class ultralong-target-residence-time p38α inhibitors as a mitosis-targeted therapy for colorectal cancer [ Nat Cancer, 2025, 6(2):259-277] PubMed: 39820127
A novel human specific lncRNA MEK6-AS1 regulates adipogenesis and fatty acid biosynthesis by stabilizing MEK6 mRNA [ J Biomed Sci, 2025, 32(1):6] PubMed: 39773638
FNDC5/irisin-enriched sEVs conjugated with bone-targeting aptamer alleviate osteoporosis: a potential alternative to exercise [ J Nanobiotechnology, 2025, 23(1):504] PubMed: 40652239
LL37 complexed to double-stranded RNA induces RIG-I-like receptor signalling and Gasdermin E activation facilitating IL-36γ release from keratinocytes [ Cell Death Dis, 2025, 16(1):198] PubMed: 40121229
Glycerophospholipid metabolism licenses IgE-mediated mast cell degranulation [ Cell Rep, 2025, 44(6):115742] PubMed: 40397574
Cannabinoid CB2 receptor controls chronic itch by regulating spinal microglial activation and synaptic transmission [ Cell Rep, 2025, 44(4):115559] PubMed: 40222011
Identification of chemical inhibitors targeting long noncoding RNA through gene signature-based high throughput screening [ Int J Biol Macromol, 2025, 292:139119] PubMed: 39722392
Lactobacillus reuteri NCHBL-005 improves wound healing by promoting the activation of fibroblasts through TLR2/MAPK signaling [ Inflamm Regen, 2025, 45(1):10] PubMed: 40211423

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人間や獣医の診断であるか治療的な使用のためにでない。

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