ST 2825
ST 2825 is a specific inhibitor of MyD88 dimerization [1].
ST 2825 is a synthetic compound which mimics the structure of the heptapeptide in the BB-loop of the MyD88-TIR domain and interferes the homodimerization of MyD88. ST 2825 was proved to specifically inhibit the homodimerization of MyD88 TIR domains without affecting the homodimerization of death domains. In HEK293T cells transfected with Flag-MyD88 and Myc-MyD88, ST 2825 inhibited the interaction of the two MyD88 by 80% at the concentration of 10 μM. This inhibition resulted in the subsequent interference of the IRAK1 and IRAK4 recruitment. Besides that, administration of ST 2825 significantly inhibited the IL-6 production stimulated by IL-1β at doses of 100 and 200 mg/kg in mice. Furthermore, 8 μM ST 2825 completely blocked the TLR9-induced B cell proliferation. ST2825 also suppressed the generation of plasma cells induced by CpG dose-dependently [1].
References:
[1] Loiarro M, Capolunghi F, Fantò N, et al. Pivotal Advance: Inhibition of MyD88 dimerization and recruitment of IRAK1 and IRAK4 by a novel peptidomimetic compound. Journal of leukocyte biology, 2007, 82(4): 801-810.
- 1. Yu Cao, Minghui Chen, et al. "Neutrophil extracellular traps mediate the crosstalk between plaque microenvironment and unstable carotid plaque formation." Exp Mol Med. 2024 Aug 1 PMID: 39085350
- 2. Sergio Ramirez-Perez, Rushi Vekariya, et al. "MyD88 dimerization inhibitor ST2825 targets the aggressiveness of synovial fibroblasts in rheumatoid arthritis patients." Arthritis Res Ther. 2023 Sep 25;25(1):180. PMID: 37749630
- 3. Katia Beider, Valeria Voevoda-Dimenshtein, et al. "CXCL13 chemokine is a novel player in multiple myeloma osteolytic microenvironment, M2 macrophage polarization, and tumor progression." J Hematol Oncol. 2022 Oct 10;15(1):144. PMID: 36217194
- 4. Alyson B. Barnes, Rachel M. Keener, et al. "Human genetic diversity regulating the TLR10/TLR1/TLR6 locus confers increased cytokines in response to Chlamydia trachomatis." HGG Adv. 2021 Nov 25;3(1):100071. PMID: 35047856
- 5. Zhao C, Zhou J, et al. "DHA Sensor GPR120 in Host Defense Exhibits the Dual Characteristics of Regulating Dendritic Cell Function and Skewing the Balance of Th17/Tregs." Int J Biol Sci. 2020 Jan 1;16(3):374-387. PMID: 32015675
- 6. Pantaleão L, Rocha GHO, et al. "Connections of annexin A1 and translocator protein-18 kDa on toll like receptor stimulated BV-2 cells." Exp Cell Res. 2018 Jun 15;367(2):282-290. PMID: 29649428
- 7. Janda J, Burkett NB, et al. "Resatorvid-based Pharmacological Antagonism of Cutaneous TLR4 Blocks UV-induced NF-κB and AP-1 Signaling in Keratinocytes and Mouse Skin." Photochem Photobiol. 2016 Nov;92(6):816-825. PMID: 27859308
- 8. Wang SH, Wang SC, et al. "Induction of cyclooxygenase-2 gene by Candida albicans through EGFR, ERK, and p38 pathways in human urinary epithelium." Med Mycol. 2016 Sep 23. PMID: 27664170
- 9. Hu LT, et al. "Role of TREM-1 in response to Aspergillus fumigatus infection in corneal epithelial cells.." Int Immunopharmacol.2014 Sep 18. pii:S1567-5769(14)00363-4. PMID: 25242387
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 591.51 |
| Cas No. | 894787-30-5 |
| Formula | C27H28Cl2N4O5S |
| Synonyms | ST2825;ST-2825 |
| Solubility | Soluble in DMSO |
| Chemical Name | (4R,7R,8aR)-1'-[2-[4-[[2-(2,4-dichlorophenoxy)acetyl]amino]phenyl]acetyl]-6-oxospiro[3,4,8,8a-tetrahydro-2H-pyrrolo[2,1-b][1,3]thiazine-7,2'-pyrrolidine]-4-carboxamide |
| SDF | Download SDF |
| Canonical SMILES | C1CC2(CC3N(C2=O)C(CCS3)C(=O)N)N(C1)C(=O)CC4=CC=C(C=C4)NC(=O)COC5=C(C=C(C=C5)Cl)Cl |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: | |
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Cell lines |
HEK 293T and HeLa cell [1], B cells and plasmacytoid dendritic cells [1] |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
6-7 h (HEK 293T cell), 15 min (HeLa cell), 5 days (B cell culture) [1] |
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Applications |
In HEK293T cells, ST2825 specifically inhibited homodimerization of MyD88 TIR domains with 40% inhibition of dimerization at 5 μM and 80% inhibition at 10 μM. This effect was specific for homodimerization of the TIR domains and did not affect homodimerization of the death domains. Moreover, ST2825 interfered with recruitment of IRAK1 and IRAK4 by MyD88, causing inhibition of IL-1-mediated activation of NF-κB transcriptional activity [1]. B cell proliferation and differentiation into plasma cells in response to CpG-induced activation of TLR9 were also suppressed by ST2825 (> 8 μM). These results showed that ST2825 blocked IL-1R/TLR signaling by interfering with MyD88 homodimerization and suggested that it may have therapeutic potential in treatment of chronic inflammatory diseases [1]. TLR9-induced plasma cell (PC) generation was blocked by ST2825 in Peripheral blood mononuclear cells from SLE patients [3]. |
| Animal experiment: | |
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Animal models |
C57BL female mice [1] |
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Dosage form |
Orally taken at 100 or 200 mg/kg/day [1]; injection at 25 mg/kg/day [2] |
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Preparation method |
ST2825 dissolved in 0.5% carboxymethylcellulose [1] |
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Applications |
IL-1 beta-induced production of IL-6 was dose-dependently inhibited by ST2825 (100 or 200mg/kg daily) in treated mice [1]. In a murine model of non-reperfused acute myocardial infarction，ST2825 (25 mg/kg) protected left ventricular from dilatation and hypertrophy. No measurable reduction in infarct size was found [2]. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Loiarro M, Capolunghi F, Fantò N et al. Pivotal advance: inhibition of MyD88 dimerization and recruitment of IRAK1 and IRAK4 by a novel peptidomimetic compound. Journal of Leukocyte Biology (2007), 82(4), 801-810. [2]. Van Tassell BW, Seropian IM, Toldo S et al. Pharmacologic Inhibition of Myeloid Differentiation Factor 88 (MyD88) Prevents Left Ventricular Dilation and Hypertrophy After Experimental Acute Myocardial Infarction in the Mouse. Journal of Cardiovascular Pharmacology (2010), 55(4), 385-390. [3]. Capolunghi F1, Rosado MM, Cascioli S et al., Pharmacological inhibition of TLR9 activation blocks autoantibody production in human B cells from SLE patients. Rheumatology (Oxford). 2010 Dec;49(12):2281-9. |
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| Description | ST 2825 is an inhibitor of MyD88 pharmacologic | |||||
| Targets | MyD88 | |||||
| IC50 | ||||||
Quality Control & MSDS
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Purity = 98.00%
- COA (Certificate Of Analysis)
- MSDS (Material Safety Data Sheet)
- Datasheet
Chemical structure
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