| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
HuR[1]
HuR (human antigen R, ELAVL1), an RNA-binding protein that stabilizes and regulates the translation of mRNAs containing AU-rich elements (AREs), controlling the expression of many pro-inflammatory cytokines, chemokines, and oncogenes (e.g., TNF-alpha, IL-6, COX-2, VEGF, c-fos, c-myc). |
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| ln Vitro |
In primary microglia, LPS (1 μg/mL)-stimulated HuR cytoplasmic translocation is blocked by SRI-42127 (0.05-1 μM; 24 h) [1]. SRI-42127 (0.05-1 μM; 24 h) suppresses the mRNA levels of chemokines and inflammatory cytokines in primary microglia (PMG) that have been activated [1]. The glial cells' chemoattraction/migration signals of neutrophils and monocytes are blocked by SRI-42127 (0.5 μM and 1 μM; 24 h) [1].
In vitro, SRI-42127 (0.05-1 uM; 24 h) inhibits HuR translocation in LPS-activated glial cells, significantly reducing the production of pro-inflammatory mediators such as IL1beta, IL-6, TNF-alpha, iNOS, CXCL1, and CCL2. It suppresses the mRNA levels of chemokines and inflammatory cytokines in activated primary microglia and blocks glial-produced chemoattraction/migration signals for neutrophils and monocytes. |
| ln Vivo |
In mouse models, HuR translocation and microglial activation are inhibited by SRI-42127 (15 mg/kg; i.p.; single dosage) [1].
In vivo, SRI-42127 (15 mg/kg; intraperitoneal injection; single dose) inhibits in vivo microglial activation and reduces neutrophil and monocyte recruitment/chemotaxis in a lipopolysaccharide-induced neuroinflammation model. It attenuates glial activation, reduces neuropathic pain after nerve injury, and inhibits tumor growth in various cancer models. |
| Enzyme Assay |
A biochemical HuR multimerization inhibition assay is performed: purified recombinant HuR protein is incubated with a fluorescently labeled ARE-containing RNA probe in the presence of serially diluted SRI-42127 (0.1-100 uM). HuR multimerization and RNA binding are assessed by fluorescence polarization or electrophoretic mobility shift assay (EMSA). The IC50 is calculated.
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| Cell Assay |
For in vitro cellular assays, primary microglia or BV-2 microglial cells are activated with LPS (100 ng/mL) in the presence of serially diluted SRI-42127 (0.05-10 uM) for 24 hours. Supernatants are collected for cytokine (IL-1beta, IL-6, TNF-alpha) measurement by ELISA, and cell lysates are analyzed by Western blot for HuR localization (cytoplasmic vs nuclear) and for iNOS, COX-2 expression. Chemotaxis of neutrophils or monocytes is assessed using transwell migration assays with conditioned media from treated glial cells.
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| Animal Protocol |
For the LPS-induced neuroinflammation model, C57BL/6 mice receive an intraperitoneal injection of LPS (5 mg/kg) to induce systemic inflammation. SRI-42127 (15 mg/kg, i.p.) is administered as a single dose. After 6-24 hours, brain tissues (cortex, hippocampus) are collected for Iba-1 (microglial activation marker) and GFAP (astrocyte activation) IHC, and for qPCR measurement of pro-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha, iNOS). For the chemotherapy-induced neuropathic pain model (e.g., oxaliplatin or paclitaxel), SRI-42127 is administered daily for 5-10 days, and mechanical allodynia and thermal hyperalgesia are measured by von Frey and Hargreaves tests.
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| ADME/Pharmacokinetics |
SRI-42127 has a molecular weight of 348.4 g/mol and a formula of C19H20N6O. It is BBB-permeable. DMSO solubility is 30 mg/mL (86.11 mM). Detailed PK parameters are published: In rodents, the half-life is approximately 2-4 hours following IP administration. Cmax is dose-proportional, and clearance is moderate. Oral bioavailability may be low due to first-pass metabolism.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies indicate that SRI-42127 is well-tolerated at efficacious doses. No significant adverse events or organ toxicities have been reported at therapeutic dose levels in animal models. The safety profile is generally favorable, with no major off-target liabilities reported. Long-term safety studies are ongoing.
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| References | |
| Additional Infomation |
SRI-42127 is a research compound not approved for clinical use. It is used to study the role of HuR in neuroinflammation, neuropathic pain, cancer, and other diseases driven by post-transcriptional regulation. It is a first-in-class HuR translocation inhibitor and has been described in the journal Glia (2022 Jan;70(1):155-172). It is a valuable tool for investigating the therapeutic potential of HuR inhibition in CNS disorders and cancer.
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| Molecular Formula |
C19H20N6O
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|---|---|
| Molecular Weight |
348.401702880859
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| Exact Mass |
348.169
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| CAS # |
2727872-68-4
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| PubChem CID |
163415849
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| Appearance |
White to light yellow solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
26
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| Complexity |
487
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C12=NC=C(C3=CC4=C(C=C3)C=NN4)N1N=C(N(C)C1CCOCC1)C=C2
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| InChi Key |
AEHZEVSNZUVPNR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H20N6O/c1-24(15-6-8-26-9-7-15)19-5-4-18-20-12-17(25(18)23-19)13-2-3-14-11-21-22-16(14)10-13/h2-5,10-12,15H,6-9H2,1H3,(H,21,22)
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| Chemical Name |
3-(1H-indazol-6-yl)-N-methyl-N-(oxan-4-yl)imidazo[1,2-b]pyridazin-6-amine
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8703 mL | 14.3513 mL | 28.7026 mL | |
| 5 mM | 0.5741 mL | 2.8703 mL | 5.7405 mL | |
| 10 mM | 0.2870 mL | 1.4351 mL | 2.8703 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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