Doramapimod (BIRB 796)

製品コードS1574 バッチS157406

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C31H37N5O3
分子量 527.66 CAS No. 285983-48-4
Solubility (25°C)* 体外 DMSO 100 mg/mL (189.51 mM)
Ethanol 100 mg/mL (189.51 mM)
Water 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.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 5.000mg/ml (9.48mM) Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Doramapimod (BIRB 796) is a pan-p38 MAPK inhibitor with IC50 of 38 nM, 65 nM, 200 nM and 520 nM for p38α/β/γ/δ in cell-free assays, and binds p38α with Kd of 0.1 nM in THP-1 cells, 330-fold greater selectivity versus JNK2, weak inhibition for c-RAF, Fyn and Lck, insignificant inhibition of ERK-1, SYK, IKK2.
in vitro

Doramapimod (BIRB 796) shows no significant inhibition to ERK-1, SYK, IKK2β, ZAP-70, EGF receptor kinase, HER2, protein kinase A (PKA), PKC, PKC-α, PKC-β (I and II) and PKC-γ. It greatly improves binding affinity by forming a hydrogen bond between the morpholine oxygen and the ATP-binding domain of p38α. This compound represents one of the most potent and slowest dissociating inhibitors against human p38 MAP kinase now known. [1]

It potently inhibits c-Raf-1 and Jnk2α2 with IC50 of 1.4 and 0.1 nM, respectively. [2]

It also inhibits the activity and the activation of SAPK3/p38γ at a higher concentration than it does in p38α. It blocks the stress-induced phosphorylation of the scaffold protein SAP97, which is a physiological substrate of SAPK3/p38γ. It blocks JNK1/2 activation and activity in HEK293 cells, while not inhibits the activation and activity of ERK1/ERK2 in Hela cells. Moreover, the binding of this compound to the p38 MAPKs or JNK1/2 is impairing their phosphorylation by the upstream kinase MKK6 or MKK4 rather than enhancing their dephosphorylation. [3]

It blocks baseline and upregulation of p38 MAPK and Hsp27 phosphorylation, thereby enhancing cytotoxicity and caspase activation. It downregulates IL-6 and VEGF secretion in BMSCs triggered by TNF-α and TGF-β1. [4]

It has a pyrazole scaffold that places a lipophilic t-butyl group into the lower selectivity site and a tolyl ring into the upper selectivity site. It also inhibits B-Raf and Abl with IC50 of 83 nM and 14.6 μM, respectively. [5]
in vivo

Doramapimod (BIRB 796) (30 mg/kg) inhibits 84% of TNF-α in LPS-stimulated mice and demonstrates efficacy in a mouse model of established collagen-induced arthritis. [1]

It has good pharmacokinetic performance even after oral administration in mice. [2]
特徴 The first p38 MAPK inhibitor to be tested in a phase III clinical trial.

プロトコル(参考用のみ)

キナーゼアッセイ Procedures for the THP-1 cellular assay for inhibition of LPS-stimulated TNF-α production
THP-1 cells are preincubated in the presence and absence of Doramapimod (BIRB 796) for 30 min. The cell mixture is stimulated with LPS (1 μg/mL final) and incubation continued overnight (18−24 hours) as above. Supernatant is analyzed for human TNF-α by a commercially available ELISA. Data are combined and analyzed by nonlinear regression using a three parameter logistic model to obtain an EC50 value. It is analyzed in each experiment and the 95% confidence intervals for the EC50 are between 16 and 22 nM.
細胞アッセイ 細胞株 Cell-free assays
濃度
反応時間
実験の流れ
動物実験 動物モデル Collagen-induced arthritis in female Balb/c mice
投薬量 1 mg/kg (intravenous) or 10 mg/kg (oral)
投与方法 Intravenous injection or by oral

参考

  • https://pubmed.ncbi.nlm.nih.gov/11896401/
  • https://pubmed.ncbi.nlm.nih.gov/12086485/
  • https://pubmed.ncbi.nlm.nih.gov/15755732/
  • https://pubmed.ncbi.nlm.nih.gov/17173546/
  • https://pubmed.ncbi.nlm.nih.gov/20621496/
  • https://pubmed.ncbi.nlm.nih.gov/14561087/

カスタマーフィードバック

Data from [Data independently produced by Int J Cancer, 2014, 134(3), 575-86]

Data from [Data independently produced by Biochem J, 2014, 449(2), 497-506]

Data from [Data independently produced by Blood, 2012, 119(26), 6255-8]

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：

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
p38 mediated ACSL4 phosphorylation drives stress-induced esophageal squamous cell carcinoma growth through Src myristoylation [ Nat Commun, 2025, 16(1):3319] PubMed: 40195298
Heparan sulfate regulates myofibroblast heterogeneity and function to mediate niche homeostasis during alveolar morphogenesis [ Nat Commun, 2025, 16(1):1834] PubMed: 39979343
Inhibition of DEK restores hematopoietic stem cell function in Fanconi anemia [ J Exp Med, 2025, 222(3)e20241248] PubMed: 39836085
Drug screening in 3D microtumors reveals DDR1/2-MAPK12-GLI1 as a vulnerability in cancer-associated fibroblasts [ Cell Rep Med, 2025, S2666-3791(25)00430-6] PubMed: 40975064
Tumor cell-released autophagosomes (TRAPs) induce PD-L1-decorated NETs that suppress T-cell function to promote breast cancer pulmonary metastasis [ J Immunother Cancer, 2024, 12(6)e009082] PubMed: 38926151
Vitamin D3 inhibits p38 MAPK and senescence-associated inflammatory mediator secretion by senescent fibroblasts that impacts immune responses during ageing [ Aging Cell, 2024, e14093.] PubMed: 38287646
Lack of p38 activation in T cells increases IL-35 and protects against obesity by promoting thermogenesis [ EMBO Rep, 2024, 10.1038/s44319-024-00149-y] PubMed: 38730210
Cetylpyridinium chloride triggers paraptosis to suppress pancreatic tumor growth via the ERN1-MAP3K5-p38 pathway [ iScience, 2024, 27(8):110598] PubMed: 39211547
Reporter cell lines to screen for inhibitors or regulators of the KRAS-RAF-MEK1/2-ERK1/2 pathway [ Biochem J, 2024, 481(6):405-422] PubMed: 38381045

長期の保管のために-20°Cの下で製品を保ってください。

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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