| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
SC99 targets the JAK2-STAT3 signaling pathway, specifically binding to the ATP-binding pocket of the JAK2 kinase. By occupying this pocket, SC99 competitively inhibits the kinase activity of JAK2, preventing the phosphorylation and subsequent activation of STAT3. This inhibition leads to the downregulation of STAT3-modulated genes that are critical for cell proliferation and survival, such as Bcl-2, Bcl-xL, VEGF, cyclin D2, and E2F-1. SC99 exhibits selectivity for the JAK2-STAT3 pathway and does not affect other kinases associated with STAT3 signaling, nor does it inhibit AKT, p65, or Src phosphorylation.
|
|---|---|
| ln Vitro |
For a duration of 72 hours, SC99 (10 or 30 μM) causes MM cell death [1]. While SC99 (10 μM; 24 h) decreased p-STAT3 levels, it had no effect on the expression of STAT3 overall. At concentrations up to 20 μM, SC99 [1] does not affect the phosphorylation levels of AKT, ERK, mTOR, or c-Src, but it does suppress JAK2 phosphorylation in a concentration-dependent manner. In a concentration-dependent manner, SC99 (1.25, 2.5, and 5 μM; 10 min pretreatment) suppresses the phosphorylation of STAT3 caused by thrombin (0.02 U/mL) and collagen (2 μg/mL) [2]. In OPM2 cells, IL-6 (50 ng/ml; 20 minutes)-induced STAT3 nuclear translocation is inhibited by SC99 two hours prior to treatment [3].
In vitro, SC99 inhibits the phosphorylation of JAK2 and STAT3 in human platelets without affecting the phosphorylation of AKT, p65, or Src, which are key factors involved in platelet activation. It inhibits human platelet aggregation induced by collagen and thrombin in a dose-dependent manner. Furthermore, SC99 inhibits thrombin-triggered P-selectin expression and fibrinogen binding to individual platelets. The compound also suppresses platelet spreading on fibrinogen and clot retraction mediated by inside-out signaling. In mouse models, SC99 inhibits platelet aggregation without significantly prolonging bleeding time. As a STAT3 inhibitor, SC99 effectively suppresses platelet activation and aggregation. |
| ln Vivo |
SC99 (30 mg/kg; oral; daily; for 14 or 28 consecutive days) slows myeloma tumor growth in xenograft animal models [1]. SC99 (5, 10, 15 mM, 15 μL; ICV) potently suppresses the phosphorylation of JAK2 and STAT3 in the middle cerebral artery occlusion-reperfusion (MCAO/R) model (adult male SD rats; 250-300 g) impact. SC99 can alleviate neuronal apoptosis and degeneration, neurobehavioral abnormalities, inflammatory reactions, and brain edema [3].
In vivo, SC99 has demonstrated anti-thrombotic activity in animal models. In mice, SC99 inhibits platelet aggregation but does not significantly prolong bleeding time, suggesting a favorable therapeutic window for anti-thrombotic applications. The compound has also been evaluated for its anti-myeloma activity, although specific in vivo efficacy data are limited. Its oral bioavailability and selective targeting of the JAK2-STAT3 pathway make it a candidate for further development in the treatment of thrombotic disorders and cancers. Additional in vivo studies would be required to fully characterize its pharmacokinetic and pharmacodynamic profiles in disease models. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cellular) assay for SC99 typically involves a kinase activity assay using recombinant JAK2 protein. The assay measures the ability of SC99 to inhibit the phosphorylation of a peptide substrate by JAK2 in the presence of ATP. Varying concentrations of SC99 are incubated with JAK2, ATP, and a substrate peptide, and the extent of phosphorylation is quantified using methods such as luminescence or fluorescence. The concentration required to achieve 50% inhibition (IC50) is determined from the dose-response curve. This assay confirms the direct binding of SC99 to the ATP-binding pocket of JAK2 and its competitive inhibition mechanism.
|
| Cell Assay |
Apoptosis analysis[1]
Cell Types: Six multiple myeloma (MM) cell lines (LP1, JJN3, RPMI-8226, U266, OPM2, and OCI-MY5) Tested Concentrations: 10 or 30 μM Incubation Duration: 72 hrs (hours) Experimental Results: Induces MM cell death. Apoptosis analysis[1] Cell Types: MM cell line[1] Tested Concentrations: 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: diminished p-STAT3 levels but had no effect on total STAT3 expression in all cell lines examined. In vitro cellular assays for SC99 are performed using human platelets or cancer cell lines. For platelet studies, human platelets are isolated and pre-incubated with varying concentrations of SC99, followed by stimulation with agonists such as collagen or thrombin. Platelet aggregation is measured using a platelet aggregometer, and the IC50 for inhibition of aggregation is determined. For cancer cell lines, cells are treated with SC99, and the phosphorylation levels of JAK2 and STAT3 are assessed by Western blotting. Cell viability, proliferation, and apoptosis are also evaluated using standard assays such as MTT, BrdU incorporation, and flow cytometry to confirm the functional consequences of STAT3 inhibition. |
| Animal Protocol |
Animal/Disease Models: Nude mice with human MM cells OPM2 or JJN3 [1]
Doses: 30 mg/kg Route of Administration: Oral; Daily; 14 or 28 days Experimental Results: Delayed myeloma tumor growth in xenograft mouse model, Inhibited tumor growth by more than 40% within 14 days in the OPM2 model. In vivo animal experiments for SC99 have been conducted in mouse models. To assess anti-thrombotic activity, mice are administered SC99 orally or via intraperitoneal injection, and platelet aggregation is measured ex vivo following agonist stimulation. Bleeding time is also measured to evaluate the risk of hemorrhage. For anti-myeloma efficacy studies, tumor-bearing mice (xenograft models) are treated with SC99, and tumor growth inhibition is monitored. Pharmacodynamic endpoints include measurement of STAT3 phosphorylation in tumor tissues, assessment of downstream gene expression, and evaluation of survival outcomes. |
| ADME/Pharmacokinetics |
SC99 is orally active and exhibits favorable pharmacokinetic properties. It is soluble in DMSO at concentrations up to 82 mg/mL (243.94 mM). For in vivo administration, SC99 can be formulated in appropriate vehicles for oral or parenteral delivery. The compound is stable as a powder at -20°C for up to 3 years and in solution at -80°C for up to 1 year. Detailed pharmacokinetic parameters such as bioavailability, half-life, Cmax, and AUC are not extensively reported in the available literature, but the compound's oral activity suggests adequate systemic exposure following oral administration.
|
| Toxicity/Toxicokinetics |
The toxicological profile of SC99 has not been extensively characterized in publicly available literature. However, the compound has been evaluated in mouse models where it inhibited platelet aggregation without significantly prolonging bleeding time, suggesting a favorable safety profile with respect to hemostasis. No significant acute or chronic toxicity has been reported. As a selective inhibitor of JAK2-STAT3, SC99 may have a lower risk of off-target effects compared to non-selective kinase inhibitors. Nevertheless, comprehensive toxicity studies would be necessary to fully assess its safety for therapeutic applications.
|
| References |
|
| Additional Infomation |
SC99 is a research compound primarily used for studying the JAK2-STAT3 signaling pathway in the context of thrombotic disorders and cancer. Its mechanism of action involves competitive inhibition of JAK2 by binding to the ATP pocket, leading to reduced STAT3 phosphorylation and downstream gene expression. SC99 has shown potent anti-myeloma and anti-thrombotic activities in preclinical studies. It is not an approved drug but serves as a valuable tool compound for elucidating the role of STAT3 in platelet function and tumor biology. Further optimization and development may lead to novel therapeutic agents for diseases with dysregulated JAK2-STAT3 signaling.
|
| Molecular Formula |
C15H8CL2FN3O
|
|---|---|
| Molecular Weight |
336.15
|
| Exact Mass |
335.002
|
| CAS # |
882290-02-0
|
| PubChem CID |
5896323
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.38±0.1 g/cm3(Predicted)
|
| Boiling Point |
459.4±55.0 °C(Predicted)
|
| LogP |
6.3
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
22
|
| Complexity |
482
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC(=CC=C1C(=O)/C(=N/NC2=CC(=C(C=C2)F)Cl)/C#N)Cl
|
| InChi Key |
ZKULFSMYRSFHKE-KGENOOAVSA-N
|
| InChi Code |
InChI=1S/C15H8Cl2FN3O/c16-10-3-1-9(2-4-10)15(22)14(8-19)21-20-11-5-6-13(18)12(17)7-11/h1-7,20H/b21-14+
|
| Chemical Name |
(1E)-N-(3-chloro-4-fluoroanilino)-2-(4-chlorophenyl)-2-oxoethanimidoyl cyanide
|
| Synonyms |
SC 99 SC-99 SC99
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~83.33 mg/mL (~247.90 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (6.19 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.08 mg/mL (6.19 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9749 mL | 14.8743 mL | 29.7486 mL | |
| 5 mM | 0.5950 mL | 2.9749 mL | 5.9497 mL | |
| 10 mM | 0.2975 mL | 1.4874 mL | 2.9749 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
