220904-83-6
220904-83-6 structure
- Name: GW5074
- Chemical Name: (3Z)-3-[(3,5-dibromo-4-hydroxyphenyl)methylidene]-5-iodo-1H-indol-2-one
- CAS Number: 220904-83-6
- Molecular Formula: C15H8Br2INO2
- Molecular Weight: 520.942
- Catalog: Biochemical Inhibitor Mitogen-activated protein kinase (MAPK) Raf inhibitor
- Create Date: 2018-08-02 09:07:13
- Modify Date: 2024-01-12 10:26:44
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GW 5074 is a potent and selective c-Raf inhibitor with IC50 of 9 nM, and has no effect on the activities of JNK1/2/3, MEK1, MKK6/7, CDK1/2, c-Src, p38 MAP, VEGFR2 or c-Fms.
| Name | (3Z)-3-[(3,5-dibromo-4-hydroxyphenyl)methylidene]-5-iodo-1H-indol-2-one |
|---|---|
| Synonyms |
gw5074
Raf1 Kinase Inhibitor I STO521 (3Z)-3-(3,5-Dibromo-4-hydroxybenzylidene)-5-iodo-1,3-dihydro-2H-indol-2-one 3-(3,5-Dibromo-4-hydroxybenzyliden)-5-iodo-1,3-dihydroindol-2-one 2H-Indol-2-one, 3-[(3,5-dibromo-4-hydroxyphenyl)methylene]-1,3-dihydro-5-iodo-, (3Z)- 5-iodo-3-((3,5-dibromo-4-hydroxyphenyl)methylene)-2-indolinone Tocris-1381 GW-5074 GW 5074 |
| Description | GW 5074 is a potent and selective c-Raf inhibitor with IC50 of 9 nM, and has no effect on the activities of JNK1/2/3, MEK1, MKK6/7, CDK1/2, c-Src, p38 MAP, VEGFR2 or c-Fms. |
|---|---|
| Related Catalog | |
| Target |
c-Raf:9 nM (IC50) |
| In Vitro | GW5074 is a potent and specific inhibitor of c-Raf with IC50 of 9 nM and has no effect of MKK6, MKK7, p38 MAP kinase and cdks in vitro. However, treatment of neuronal cultures with GW5074 permits accumulation of activating modifications on c-Raf and also B-Raf. The inhibition of LK-induced apoptosis by GW5074 in cerebellar granule neurons is not MEK-ERK-dependent. GW5074 delays down-regulation of Akt activity but inhibits apoptosis by an Akt-independent mechanism. GW5074 affects Ras, nuclear factor-kappa B and c-jun. GW5074 inhibits cell death caused by neurotoxins in granule cells and other neuronal types[1]. |
| In Vivo | GW5074 (5 mg/Kg) completely prevents extensive bilateral striatal lesions induced by 3-NP in mice[1]. GW5074 suppresses sidestream smoke-induced airway hyperresponsiveness in mice[2]. GW5074 completely abolishes chronic morphine-mediated AC superactivation I in CHO cells stably expressing the humanμ-opioid receptor[3]. |
| Kinase Assay | Briefly, for each assay 5-10 mU of purified kinase is used. For GSK3β, cdk1, cdk2, cdk3, cdk5, the kinase is incubated with 1 μM GW5074 in a buffer containing 8 mM MOPS, pH 7.2, 0.2 mM EDTA, 10 mM magnesium acetate and [c-33P-ATP] for 40 min at room temperature. Kinase activity is quantified by measuring 33P incorporation by spotting an aliquot on P30 filters, washing in 50 mM phosphoric acid and scintillation counting. The buffer composition for c-Raf, JNK1, JNK2, JNK3, MEK1, MKK6, MKK7 is 50 mM Tris pH 7.5, 0.1 mM EGTA, 10 mM magnesium acetate and [c-33P-ATP]. The peptide substrates used are as follows: For c-Raf, 0.66 mg/mL MBP; for cdks, 0.1 mg/mL histone H1; for JNKs, 3 μM ATF2; for MEK1, 1 μM MAPK2; for MKK6, 1 μM of SAPK2a and for MKK7, 2 μM JNK1α. |
| Cell Assay | Befiy, the tetrazolium salt MTT is added to the cultures at a final concentration of 1 mg/mL, and incubation of the culture is continued in the CO2 incubator for a Hirther 30 min at 37°C. The assay is stopped by adding lysis buffer [20% sodium dodecyi sulfate (SDS) in 50% N,N-dimethyl formamide, pH 4.7], The absorbance is measured spectrophotometrically at 570 nm after an ovemight incubation at room temperature. The absorbance of a well without cells is used as background and subtracted. Data are presented as mean±standard deviation. Statistical analysis is perfomied using ANOVA and Student-Neuman-Keuls' test. Besides MTT assays, viability is also quantitied using the tluorescein-diacetate method and by DAPI staining (which reveals apoptotic nuclei as condensed or fragmented). The results using these assays are similar to those obtained with the MTT assay. |
| Animal Admin | The Tru-Scan® activity monitoring system is used to assess locomotor activity on mice on the day following the 5 days of injection with saline, 3-NP or a combination of 3-NP and GW5074 (7 animals in each group). The animal is placed in a Perspex arena (25.9×25.9 cm) witb infrared beams spaced at 0.6-inch intervals in the X-Y plane. The arena is also equipped with a second infrared beam system at the Z plane positioned 2.54 cm above the X-Y plane. In this system the movement of the animal is accurately assessed by interruptions in 17×17-grid system created by the infrared beams in both the X-Y and Z planes. The animal is allowed to remain in the arena for 15 min, with data collection performed during this period using the Tru Scan Line interface box and Tm Scan 99 software, operating through a Pentium PC. The following behavioral parameters are selected: (i) Total movements episodes: each movement in the flor plane is a series of coordinate changes with no rest for at least I sample interval; (ii) total movement distance: the sum of all vectored A-Y coordinate changes in the floor plane; (iii) mean velocity: the mean velocity of all X-Y coordinate change defined movements; and (iv) vertical plane entries: the total number of times any part of the animal entered the vertical plane (Z plane). |
| References |
| Density | 2.2±0.1 g/cm3 |
|---|---|
| Boiling Point | 561.4±50.0 °C at 760 mmHg |
| Molecular Formula | C15H8Br2INO2 |
| Molecular Weight | 520.942 |
| Flash Point | 293.3±30.1 °C |
| Exact Mass | 518.796631 |
| PSA | 49.33000 |
| LogP | 6.36 |
| Vapour Pressure | 0.0±1.6 mmHg at 25°C |
| Index of Refraction | 1.790 |
| Storage condition | -20°C |
| Water Solubility | DMSO: soluble |
| Personal Protective Equipment | Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter |
|---|---|
| RIDADR | NONH for all modes of transport |
| WGK Germany | 3 |