SPD304 |
Katalog-Nr.GC33133
One-Click Copy Product Info
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SPD304 ist ein selektiver TNF-α-Inhibitor, der die Dissoziation von TNF-Trimeren fÖrdert und somit die Interaktion von TNF und seinem Rezeptor blockiert. SPD304 hat einen IC50-Wert von 22 μM zur Hemmung der In-vitro-TNF-Rezeptor-1 (TNFR1)-Bindung an TNF-α.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 869998-49-2
Sample solution is provided at 25 µL, 10mM.
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SPD304 is a selective inhibitor of tumor necrosis factor α (TNF-α), with an IC50 value of 22μM[1]. SPD304 promotes dissociation of TNF trimers and therefore blocks the interaction of TNF and the related receptor [2]. SPD304 has been widely used to block the TNF-α/NF-κB/CUL4B pathway to induce cell cycle arrest in S phase [3].
In vitro, SPD304 treatment at 30µM for 24h significantly induced HEK293T cell death[4]. Treatment with 25µM SPD304 for 24h significantly inhibited TNFα activity and reduced L929 cell viability[5]. Treatment of GH3 cells with 8µM SPD304 for 48h inhibited TNFα-induced upregulation of MAPK pathway proteins and inhibited cell proliferation, migration, and invasion[6]. Preincubation with 1µM SPD304 for 24 hours significantly inhibited IL-8 and IL-6 levels in human dermal fibroblasts (HDFs)[7].
In vivo, SPD304 treatment (5µg; dissolved in 10µl artificial cerebrospinal fluid containing 5% DMSO) via intracerebroventricular injection for 5min inhibited the increase in blood pressure, heart rate, and renal sympathetic activity induced by TACE (TNF-α–converting enzyme) in heart failure rats[8].
References:
[1] He M M, Smith A S, Oslob J D, et al. Small-molecule inhibition of TNF-α[J]. Science, 2005, 310(5750): 1022-1025.
[2] Alexiou P, Papakyriakou A, Ntougkos E, et al. Rationally designed less toxic SPD‐304 analogs and preliminary evaluation of their TNF inhibitory effects[J]. Archiv der Pharmazie, 2014, 347(11): 798-805.
[3] Zhang C, Chen B, Jiang K, et al. Activation of TNF‐α/NF‐κB axis enhances CRL 4 BDCAF 11 E3 ligase activity and regulates cell cycle progression in human osteosarcoma cells[J]. Molecular oncology, 2018, 12(4): 476-494.
[4] Shen Q, Zhang C, Liu H, et al. De novo design of helical peptides to inhibit tumor necrosis factor-α by disrupting its trimer formation[J]. MedChemComm, 2016, 7(4): 725-729.
[5] Mascret A, Mouhsine H, Attia G, et al. New contributions to the drug profile of TNFα inhibitor SPD304: Affinity, selectivity and ADMET considerations[J]. European Journal of Pharmacology, 2021, 907: 174285.
[6] Wu X, Gong L, Li B, et al. TNF‐α can promote membrane invasion by activating the MAPK/MMP9 signaling pathway through autocrine in bone‐invasive pituitary adenoma[J]. CNS Neuroscience & Therapeutics, 2024, 30(5): e14749.
[7] Javaid N, Patra M C, Cho D E, et al. An orally active, small-molecule TNF inhibitor that disrupts the homotrimerization interface improves inflammatory arthritis in mice[J]. Science Signaling, 2022, 15(759): eabi8713.
[8] Yu Y, Cao Y, Bell B, et al. Brain TACE (tumor necrosis factor-α–converting enzyme) contributes to sympathetic excitation in heart failure rats[J]. Hypertension, 2019, 74(1): 63-72.
| Cell experiment [1]: | |
Cell lines | HEK293T cells |
Preparation Method | HEK293T cells were plated in 96-well plates at 1×104 cells per well and cultured in 100μl of DMEM at 37°C for 24 hours. Then, to each well was added 50μl of SPD304 at various concentrations (1, 10, 20, 40, 60, 80, and 100µM). In the control groups, 50μl of DMEM was used. Wells containing only media without cells and additives were used as blanks. Cell viability was measured after 24 hours. |
Reaction Conditions | 1, 10, 20, 40, 60, 80, and 100µM; 24h |
Applications | SPD304 treatment significantly the cell viability of HEK293T cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Male Sprague-Dawley rats |
Preparation Method | Male Sprague-Dawley rats (225-275g) were housed in temperature (23±2°C) and light-controlled (12:12-hour light-dark cycle) animal care facility. Heart failure (HF) and sham-operated (Sham) rats were produced by coronary artery ligation or sham surgery. Sham (n=6) and HF (n=6) rats were treated with intracerebroventricular injection of TACE (300ng in 3µl artificial cerebrospinal fluid over 1 minute) immediately after intracerebroventricular pretreatment with the SPD304 (5µg in 10µl 5% DMSO in artificial cerebrospinal fluid over 5 minutes). Mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were analyzed. |
Dosage form | 5µg for once; i.c.v. |
Applications | SPD304 treatment inhibited the increase in blood pressure, HR, and RSNA induced by TACE in HF rats. |
References: | |
| Cas No. | 869998-49-2 | SDF | |
| Canonical SMILES | O=C1C(CN(C)CCN(C)CC2=CN(C3=CC=CC(C(F)(F)F)=C3)C4=C2C=CC=C4)=COC5=CC(C)=C(C)C=C15 | ||
| Formula | C32H32F3N3O2 | M.Wt | 547.61 |
| Löslichkeit | DMSO : 25 mg/mL (45.65 mM) Water : 20 mg/mL (36.52 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8261 mL | 9.1306 mL | 18.2612 mL |
| 5 mM | 365.2 μL | 1.8261 mL | 3.6522 mL |
| 10 mM | 182.6 μL | 913.1 μL | 1.8261 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 28 reference(s) in Google Scholar.)