| 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 | |||
| Other Sizes |
| Targets |
FGFR1 (fibroblast growth factor receptor 1) – IC50 = 10-20 μM (in vitro autophosphorylation assay in the presence of 1 mM ATP); IC50 = 20-40 μM (in vivo autophosphorylation in NIH 3T3 cells) [1]
KIT (wild-type and juxtamembrane mutants) – inhibits wild-type KIT and KIT with juxtamembrane activating mutations [2] PDGFR – inhibits platelet-derived growth factor receptor [2] Insulin receptor – inhibits insulin receptor [2] EGFR (epidermal growth factor receptor) – no inhibition up to 200 μM [1] |
|---|---|
| ln Vitro |
In Vitro: SU4984 inhibited the autophosphorylation activity of purified FGFR1 kinase domain (FGFR1K) with an IC50 of 10-20 μM in the presence of 1 mM ATP, as determined by in vitro kinase assay using [γ-32P]ATP. [1]
SU4984 inhibited aFGF-induced FGFR1 autophosphorylation in NIH 3T3 cells with an IC50 of 20-40 μM. It also inhibited aFGF-induced tyrosine phosphorylation of pp90 and MAP kinases (ERK1 and ERK2) with similar IC50 values. [1] SU4984 inhibited aFGF-induced [3H]thymidine incorporation in NIH 3T3 cells at 50 μM. [1] SU4984 inhibited tyrosine phosphorylation of the PDGF receptor and the insulin receptor, but did not inhibit EGF receptor phosphorylation even at concentrations up to 200 μM. [1] SU4984 inhibited wild-type KIT and KIT with juxtamembrane activating mutations, but was less effective against KIT with kinase domain mutations (e.g., D816V). [2] SU4984 killed neoplastic mast cells expressing juxtamembrane-mutated KIT, as well as neoplastic mast cells expressing KIT bearing a kinase domain mutation (e.g., P815 cells with D814Y mutation). [2] In the presence of 1 mM adenosine triphosphate (ATP), SU4984 (5-100 μM; 5 minutes) suppresses the kinase activity of FGFR1K with an IC50 of 10-20 μM [1]. With an IC50 of 20–40 μM, SU4984 (10–90 μM; 5 minutes) prevents aFGF-induced autophosphorylation of FGFR1 in NIH 3T3 cells [1]. 50% less constitutive C2 KIT phosphorylation and a considerable reduction in wild-type receptor tyrosine phosphorylation are observed when SU4984 (5 μM) is used [2]. C2 and P815 cells are killed by SU4984 (1–10 μM; 6 days) [2]. |
| Enzyme Assay |
Enzyme Assay: In vitro kinase assay for FGFR1K: FGFR1K (2.2 mg/ml in 10 mM Tris pH 8, 10 mM NaCl) was mixed with various concentrations of SU4984 (diluted from 100 mM DMSO stock) or DMSO control. The reaction was started by adding the enzyme-compound mixture to 2× kinase buffer (2 mM ATP/[γ-32P]ATP (10 μCi/μl), 4 mM MgCl2 in 10 mM Tris pH 8, 10 mM NaCl) at room temperature. At various time points, aliquots were removed and added to 20 mM EDTA to stop the reaction. Reaction products were analyzed by SDS-PAGE (12% gel) and autoradiography. Radioactive bands were excised and 32P incorporation was quantified by Cerenkov counting. [1]
Crystallographic studies: Crystals of native FGFR1K were soaked in stabilizing solution containing 5 mM SU4984 at 4°C for 24-48 hours. Data were collected on a rotating anode X-ray generator. Difference Fourier electron density maps were computed using phases from the unliganded FGFR1K structure. The structure was refined using simulated annealing and conjugate-gradient minimization. [1] |
| Cell Assay |
Cell Assay: NIH 3T3 cells expressing endogenous FGF receptors were used. Cells were incubated with various concentrations of SU4984 for 5 min at 37°C, then stimulated with aFGF (100 ng/ml) and heparin (10 μg/ml) for 5 min at 37°C. Cell lysates were immunoprecipitated with anti-FGFR1 antibodies, separated by SDS-PAGE, and immunoblotted with anti-phosphotyrosine antibodies or anti-FGFR1 antibodies. [1]
For [3H]thymidine incorporation, NIH 3T3 cells were treated with SU4984 (50 μM) or untreated, stimulated with aFGF, then labeled with [3H]thymidine. Thymidine incorporation was measured after 24 hours. [1] For PDGFR, insulin receptor, and EGFR assays: NIH 3T3 cells (PDGFR), NIHIR cells (insulin receptor), or HER14 cells (EGFR) were incubated with various concentrations of SU4984 for 5 min at 37°C, then stimulated with PDGF (40 ng/ml), insulin (1 μg/ml), or EGF (100 ng/ml) for 5 min at 37°C. Cell lysates were immunoprecipitated with receptor-specific antibodies and immunoblotted with anti-phosphotyrosine antibodies. [1] KIT activity assay: KIT phosphorylation was determined by in vivo phosphorylation assays. Neoplastic mast cell lines C2 (expressing juxtamembrane-mutated KIT) and P815 (expressing D814Y kinase domain mutation) were used. Cells were treated with SU4984 and cell viability was assessed. [2] |
| References | |
| Additional Infomation |
SU4984 (3-[4-(1-formylpiperazin-4-yl)benzylidenyl]-2-indolinone) is an oxindole-based protein tyrosine kinase inhibitor. It was prepared by reacting oxindole with 4-(1-formylpiperazin-4-yl)benzaldehyde in ethanol with piperidine at 90°C for 5 hours, yielding 65% as a yellow solid. NMR spectroscopy showed that SU4984 exists predominantly in the trans configuration, although in the crystal structure it is observed in the cis configuration. [1]
In the crystal structure of FGFR1K in complex with SU4984 (2.4 Å resolution), the oxindole occupies the ATP adenine binding site and makes two hydrogen bonds to the protein backbone: between N-1 of the oxindole and the carbonyl oxygen of Glu562, and between O-2 of the oxindole and the amide nitrogen of Ala564. The phenyl ring makes an oxygen-aromatic contact with the carbonyl oxygen of Ala564. The piperazine ring is in van der Waals contact with Gly567. [1] SU4984 has a relatively broad spectrum of inhibition, being effective against FGFR, PDGFR, insulin receptor, and KIT. It does not inhibit EGFR. [1][2] SU4984 is a substance that can inhibit the tyrosine kinase activity of fibroblast growth factor receptor 1, tyrosine phosphorylation of PDGF receptor, and insulin receptor. (National Cancer Institute) |
| Molecular Formula |
C20H19N3O2
|
|---|---|
| Molecular Weight |
333.38376
|
| Exact Mass |
333.148
|
| Elemental Analysis |
C, 72.05; H, 5.74; N, 12.60; O, 9.60
|
| CAS # |
186610-89-9
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| PubChem CID |
5941540
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| Appearance |
Yellow solid powder
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| Density |
1.34g/cm3
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| Boiling Point |
649.1ºC at 760 mmHg
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| Flash Point |
346.4ºC
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| Vapour Pressure |
9.81E-17mmHg at 25°C
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| Index of Refraction |
1.72
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| LogP |
3.234
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
25
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| Complexity |
531
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C1/C(=C/C2C=CC(N3CCN(C=O)CC3)=CC=2)/C2C(=CC=CC=2)N1
|
| InChi Key |
ZNFJBJDODKHWED-AQTBWJFISA-N
|
| InChi Code |
InChI=1S/C20H19N3O2/c24-14-22-9-11-23(12-10-22)16-7-5-15(6-8-16)13-18-17-3-1-2-4-19(17)21-20(18)25/h1-8,13-14H,9-12H2,(H,21,25)/b18-13-
|
| Chemical Name |
4-[4-[(Z)-(2-oxo-1H-indol-3-ylidene)methyl]phenyl]piperazine-1-carbaldehyde
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| Synonyms |
SU 4984; SU4984; RefChem:932326; 186610-89-9; SU4984
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~50 mg/mL (~149.98 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (15.00 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 sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 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 | 2.9996 mL | 14.9979 mL | 29.9958 mL | |
| 5 mM | 0.5999 mL | 2.9996 mL | 5.9992 mL | |
| 10 mM | 0.3000 mL | 1.4998 mL | 2.9996 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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