Synonym
GW5074; GW 5074; GW-5074;
IUPAC/Chemical Name
3-(3,5-Dibromo-4-hydroxy-benzylidene)-5-iodo-1,3-dihydro-indol-2-one
InChi Key
LMXYVLFTZRPNRV-KMKOMSMNSA-N
InChi Code
InChI=1S/C15H8Br2INO2/c16-11-4-7(5-12(17)14(11)20)3-10-9-6-8(18)1-2-13(9)19-15(10)21/h1-6,20H,(H,19,21)/b10-3-
SMILES Code
O=C1NC2=C(C=C(I)C=C2)/C1=C/C3=CC(Br)=C(O)C(Br)=C3
Purity
≥98% (mixture of cis and trans)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>5 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
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.
In vitro activity:
These studies showed that GW5074 exhibited selective antimicrobial activity toward Gram-positive micro-organisms with MICs ranging from 2 to 8 μg/ml, compared with the >64 μg/ml for all Gram-negative bacteria tested (Tables 2 & 3).
Reference: Future Med Chem. 2016 Oct;8(16):1941-1952. https://pubmed.ncbi.nlm.nih.gov/27652456/
In vivo activity:
As shown in Fig. 10 (top panel), mice administered 3-NP display extensive bilateral striatal lesions. This degeneration is completely prevented by GW5074 when administered at a concentration of 5 mg/kg body weight. Administration of GW5074 alone had no discernible effect on the animals as judged by behavior and cell morphology of brain sections (data not shown).
Reference: Neurochem. 2004 Aug;90(3):595-608. https://pubmed.ncbi.nlm.nih.gov/15255937/
|
Solvent |
mg/mL |
mM |
Solubility |
DMF |
15.0 |
28.79 |
DMSO |
73.0 |
140.13 |
DMSO:PBS (pH 7.2) (1:8) |
0.1 |
0.19 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
520.95
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Johnston T, Hendricks GL, Shen S, Chen RF, Kwon B, Kelso MJ, Kim W, Burgwyn Fuchs B, Mylonakis E. Raf-kinase inhibitor GW5074 shows antibacterial activity against methicillin-resistant Staphylococcus aureus and potentiates the activity of gentamicin. Future Med Chem. 2016 Oct;8(16):1941-1952. doi: 10.4155/fmc-2016-0104. Epub 2016 Sep 21. PMID: 27652456; PMCID: PMC5619112.
2. Chin PC, Liu L, Morrison BE, Siddiq A, Ratan RR, Bottiglieri T, D'Mello SR. The c-Raf inhibitor GW5074 provides neuroprotection in vitro and in an animal model of neurodegeneration through a MEK-ERK and Akt-independent mechanism. J Neurochem. 2004 Aug;90(3):595-608. doi: 10.1111/j.1471-4159.2004.02530.x. PMID: 15255937.
In vitro protocol:
1. Johnston T, Hendricks GL, Shen S, Chen RF, Kwon B, Kelso MJ, Kim W, Burgwyn Fuchs B, Mylonakis E. Raf-kinase inhibitor GW5074 shows antibacterial activity against methicillin-resistant Staphylococcus aureus and potentiates the activity of gentamicin. Future Med Chem. 2016 Oct;8(16):1941-1952. doi: 10.4155/fmc-2016-0104. Epub 2016 Sep 21. PMID: 27652456; PMCID: PMC5619112.
2. Chin PC, Liu L, Morrison BE, Siddiq A, Ratan RR, Bottiglieri T, D'Mello SR. The c-Raf inhibitor GW5074 provides neuroprotection in vitro and in an animal model of neurodegeneration through a MEK-ERK and Akt-independent mechanism. J Neurochem. 2004 Aug;90(3):595-608. doi: 10.1111/j.1471-4159.2004.02530.x. PMID: 15255937.
In vivo protocol:
1. Johnston T, Hendricks GL, Shen S, Chen RF, Kwon B, Kelso MJ, Kim W, Burgwyn Fuchs B, Mylonakis E. Raf-kinase inhibitor GW5074 shows antibacterial activity against methicillin-resistant Staphylococcus aureus and potentiates the activity of gentamicin. Future Med Chem. 2016 Oct;8(16):1941-1952. doi: 10.4155/fmc-2016-0104. Epub 2016 Sep 21. PMID: 27652456; PMCID: PMC5619112.
2. Chin PC, Liu L, Morrison BE, Siddiq A, Ratan RR, Bottiglieri T, D'Mello SR. The c-Raf inhibitor GW5074 provides neuroprotection in vitro and in an animal model of neurodegeneration through a MEK-ERK and Akt-independent mechanism. J Neurochem. 2004 Aug;90(3):595-608. doi: 10.1111/j.1471-4159.2004.02530.x. PMID: 15255937.
1: Suenkel B, Fischer F, Steegborn C. Inhibition of the human deacylase Sirtuin 5 by the indole GW5074. Bioorg Med Chem Lett. 2013 Jan 1;23(1):143-6. doi: 10.1016/j.bmcl.2012.10.136. Epub 2012 Nov 12. PubMed PMID: 23195732.
2: Li J, Fan Y, Zhang YN, Sun DJ, Fu SB, Ma L, Jiang LH, Cui C, Ding HF, Yang J. The Raf-1 inhibitor GW5074 and the ERK1/2 pathway inhibitor U0126 ameliorate PC12 cells apoptosis induced by 6-hydroxydopamine. Pharmazie. 2012 Aug;67(8):718-24. PubMed PMID: 22957439.
3: Lei Y, Cao YX, Xu CB, Zhang Y. The Raf-1 inhibitor GW5074 and dexamethasone suppress sidestream smoke-induced airway hyperresponsiveness in mice. Respir Res. 2008 Nov 3;9:71. doi: 10.1186/1465-9921-9-71. PubMed PMID: 18976506; PubMed Central PMCID: PMC2599896.
4: Chen HM, Wang L, D'Mello SR. Inhibition of ATF-3 expression by B-Raf mediates the neuroprotective action of GW5074. J Neurochem. 2008 May;105(4):1300-12. doi: 10.1111/j.1471-4159.2008.05226.x. Epub 2008 Jan 10. PubMed PMID: 18194435.
5: Yue X, Varga EV, Stropova D, Vanderah TW, Yamamura HI, Roeske WR. Chronic morphine-mediated adenylyl cyclase superactivation is attenuated by the Raf-1 inhibitor, GW5074. Eur J Pharmacol. 2006 Jul 1;540(1-3):57-9. Epub 2006 May 3. PubMed PMID: 16750187.
6: Chin PC, Liu L, Morrison BE, Siddiq A, Ratan RR, Bottiglieri T, D'Mello SR. The c-Raf inhibitor GW5074 provides neuroprotection in vitro and in an animal model of neurodegeneration through a MEK-ERK and Akt-independent mechanism. J Neurochem. 2004 Aug;90(3):595-608. PubMed PMID: 15255937.