| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| Targets |
4SC-203 is a multi-target kinase inhibitor that primarily targets FMS-like tyrosine kinase 3 (FLT3/STK1) and its mutated forms, as well as vascular endothelial growth factor receptors (VEGFRs). Additionally, the compound exhibits selective inhibitory activity against Axl, Alk, Fak, VEGF-R2, and Trk receptors in the low nanomolar range. FLT3 is overexpressed in acute myeloid leukemia patients, and FLT3 mutations can be identified in approximately one-third of AML patients, which are associated with a high relapse rate and poor prognosis. VEGFRs play a critical role in angiogenesis and tumor growth.
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| ln Vitro |
In vitro studies have shown that 4SC-203 effectively inhibits the kinase activity of wild-type FLT3 and various mutant forms (e.g., FLT3-ITD, FLT3-D835Y) in the low nanomolar concentration range, while also potently inhibiting VEGFR-2. Furthermore, the compound inhibits the activity of other kinases including Axl, Alk, Fak, and Trk, with IC₅₀ values in the low nanomolar range. In FLT3-driven leukemia cell lines, 4SC-203 dose-dependently inhibits cell proliferation and induces apoptosis. In angiogenesis-related functional assays, 4SC-203 inhibits VEGF-stimulated endothelial cell proliferation and tube formation.
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| ln Vivo |
In animal models related to acute myeloid leukemia, 4SC-203 demonstrates significant antitumor in vivo activity. In FLT3-ITD mutant AML xenograft mouse models, 4SC-203 administration significantly inhibits tumor growth and reduces tumor volume. Preclinical studies have also confirmed that 4SC-203 simultaneously inhibits both tumor cell proliferation and tumor angiogenesis pathways, achieving dual antitumor effects. Additionally, in the first-in-human Phase I study conducted in healthy volunteers, 4SC-203 showed favorable safety and tolerability profile across the investigated dose ranges, with no target organ toxicity observed.
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| Enzyme Assay |
Typical kinase inhibition assays employ radiolabeled filter-binding methods or microfluidic mobility shift assays. The procedure is as follows: purified recombinant kinases (e.g., FLT3, VEGFR-2) are mixed with appropriate concentrations of ATP and substrate peptides in kinase reaction buffer, followed by addition of serially diluted 4SC-203 (typically starting at 10 μM, 3-fold serial dilutions, 10 concentration points). The mixture is incubated at room temperature or 30°C for 60 minutes. After termination of the reaction, the mixture is transferred to a filter membrane, washed to remove unbound ATP and free substrates, and radioactivity on the membrane is detected using a scintillation counter or imaging system. Dose-response curves are fitted by nonlinear regression to calculate IC₅₀ values. ATP concentration should be set close to the Km value for the corresponding kinase, and reaction conditions must ensure linear product generation rates.
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| Cell Assay |
Cell proliferation inhibition assays are typically performed using the CCK-8 or MTS method. The procedure is as follows: FLT3 mutation-positive leukemia cells in logarithmic growth phase (e.g., MV4-11, MOLM-14 cell lines) are seeded into 96-well plates at a density of approximately 5,000-10,000 cells/well. After overnight incubation at 37°C in a 5% CO₂ incubator to allow cell adhesion, serially diluted 4SC-203 is added (common concentration range: 0.01 nM, 0.1 nM, 1 nM, 10 nM, 100 nM, 1 μM, 10 μM), with three replicate wells per concentration. Following an additional 48-72 hours of culture, 10 μL of CCK-8 reagent is added to each well and incubated for 1-4 hours, and absorbance is measured at 450 nm. Cell viability inhibition rates and IC₅₀ values are calculated using GraphPad Prism software. Vehicle control (DMSO) and positive control (e.g., the standard FLT3 inhibitor quizartinib) are also included.
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| Animal Protocol |
In vivo efficacy studies are typically performed using FLT3-ITD mutant xenograft models. The procedure is as follows: MV4-11 or MOLM-14 human acute myeloid leukemia cells (approximately 5×10⁶ cells suspended in 100 μL PBS) are subcutaneously inoculated into the right flank of 6-8 week old female BALB/c nude mice or NSG mice. When tumor volumes reach approximately 100-150 mm³, animals are randomized into groups (n=8-10 per group), including: negative control group (vehicle control), positive control group (standard FLT3 inhibitor such as quizartinib or sorafenib), and 4SC-203 low-, medium-, and high-dose groups (e.g., 0.5, 1.5, 5 mg/kg). 4SC-203 is administered intravenously, typically once daily or every other day, for 2-3 consecutive weeks. Tumor volumes (length × width² × 0.5) and body weights are measured 2-3 times per week, and tumor growth inhibition rates (TGI%) are calculated. At study completion, tumor and plasma samples are collected for pharmacodynamic biomarker analysis (e.g., FLT3 phosphorylation levels) and PK correlation studies.
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| ADME/Pharmacokinetics |
Pharmacokinetic evaluation of 4SC-203 was completed in a double-blind, randomized, placebo-controlled Phase I dose-escalation study conducted in healthy male volunteers. The study included 60 volunteers, and 4SC-203 was administered as a single intravenous dose across a dose range of 0.041 to 2.5 mg/kg (equivalent to a total single dose of 2.5 to 150 mg for a 60 kg individual). Pharmacokinetic analysis demonstrated that systemic exposure of 4SC-203 displayed the expected dose-dependent increase over the investigated concentration range of applied doses. This favorable pharmacokinetic profile provided an excellent basis for further clinical development of the compound.
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| Toxicity/Toxicokinetics |
In the first-in-human Phase I study in healthy volunteers, 4SC-203 demonstrated favorable safety and tolerability. Only 33% of volunteers experienced adverse events, all of which were graded as mild intensity with the exception of three events graded as moderate. No dose-dependent increase in treatment-emergent adverse events was observed, no serious adverse events occurred, and there were no changes in physical and laboratory parameters or target organ toxicity. In safety data sheets, 4SC-203 is classified as toxic and contains a pharmaceutically active ingredient, with handling limited to trained personnel. The compound is a moderate to severe irritant to skin and eyes, and may emit toxic fumes such as carbon monoxide and nitrogen oxides upon combustion.
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| References | |
| Additional Infomation |
4SC-203 has been used in clinical trials for the treatment of acute myeloid leukemia (AML). The multi-kinase inhibitor 4SC-203 is a multi-kinase inhibitor with potential anti-tumor activity. 4SC-203 selectively inhibits FMS-associated tyrosine kinase 3 (FLT3/STK1), FLT3 mutants, and vascular endothelial growth factor receptor (VEGFR). This may lead to inhibition of angiogenesis and cell proliferation in tumor cells upregulated by these kinases. FLT3 (FLK2) is a class III tyrosine kinase receptor that is overexpressed or mutated in most B cell lines and acute myeloid leukemia (AML). VEGFR is a tyrosine kinase receptor that is overexpressed in various tumor cell types and plays a crucial role in angiogenesis.
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| Molecular Formula |
C33H38N8O4S
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|---|---|
| Molecular Weight |
642.77
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| Exact Mass |
642.274
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| CAS # |
895533-09-2
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| PubChem CID |
44467821
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| Appearance |
White to off-white solid powder
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| LogP |
6.063
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
46
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| Complexity |
963
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
MAFACRSJGNJHCF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C33H38N8O4S/c1-21-6-9-27(43-3)26(16-21)37-32(42)39-33-38-24-8-7-22(17-30(24)46-33)36-31-23-18-28(44-4)29(19-25(23)34-20-35-31)45-15-5-10-41-13-11-40(2)12-14-41/h6-9,16-20H,5,10-15H2,1-4H3,(H,34,35,36)(H2,37,38,39,42)
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| Chemical Name |
1-(2-methoxy-5-methylphenyl)-3-(6-((6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazolin-4-yl)amino)benzo[d]thiazol-2-yl)urea
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| Synonyms |
4SC203 4SC 2034SC-203 SC 71710SC71710 SC-71710
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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) |
DMSO : ~125 mg/mL (~194.47 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
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 (3.24 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. 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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5558 mL | 7.7788 mL | 15.5577 mL | |
| 5 mM | 0.3112 mL | 1.5558 mL | 3.1115 mL | |
| 10 mM | 0.1556 mL | 0.7779 mL | 1.5558 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01054937 | COMPLETED | Drug: 4SC-203 Drug: Placebo |
Acute Myeloid Leukemia | 4SC AG | 2010-01 | Phase 1 |
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