Synonym
L779450; L-779450; L 779450; L779,450; L 779,450; L-779,450.
IUPAC/Chemical Name
2-chloro-5-(2-phenyl-5-(pyridin-4-yl)-1H-imidazol-4-yl)phenol
InChi Key
WXJLXRNWMLWVFB-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H14ClN3O/c21-16-7-6-15(12-17(16)25)19-18(13-8-10-22-11-9-13)23-20(24-19)14-4-2-1-3-5-14/h1-12,25H,(H,23,24)
SMILES Code
OC1=CC(C2=C(C3=CC=NC=C3)NC(C4=CC=CC=C4)=N2)=CC=C1Cl
Purity
>98% (or refer to the Certificate of Analysis)
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
>2 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:
L-779450 is a potent and selective B-Raf kinase inhibitor with a Kd of 2.4 nM.
In vitro activity:
The pan-RAF inhibitor L-779,450 was applied for understanding the relations of RAF inhibition and apoptosis regulation in melanoma cells. Strong and dose-dependent phosphorylated ERK (pERK) downregulation was seen by L-779,450 in the BRAF(V600E)-mutated, TRAIL-sensitive melanoma cell line A-375, as well as in TRAIL-resistant A-375-TS.
Reference: J Invest Dermatol. 2014 Feb;134(2):430-440. https://pubmed.ncbi.nlm.nih.gov/23955071/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
44.7 |
128.44 |
| DMF |
30.0 |
86.26 |
| DMF:PBS (pH 7.2) (1:7) |
0.1 |
0.35 |
| Ethanol |
2.0 |
5.75 |
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
347.80
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. Berger A, Quast SA, Plötz M, Kuhn NF, Trefzer U, Eberle J. RAF inhibition overcomes resistance to TRAIL-induced apoptosis in melanoma cells. J Invest Dermatol. 2014 Feb;134(2):430-440. doi: 10.1038/jid.2013.347. Epub 2013 Aug 16. PMID: 23955071.
In vitro protocol:
1. Berger A, Quast SA, Plötz M, Kuhn NF, Trefzer U, Eberle J. RAF inhibition overcomes resistance to TRAIL-induced apoptosis in melanoma cells. J Invest Dermatol. 2014 Feb;134(2):430-440. doi: 10.1038/jid.2013.347. Epub 2013 Aug 16. PMID: 23955071.
1: Geserick P, Herlyn M, Leverkus M. On the TRAIL to overcome BRAF-inhibitor resistance. J Invest Dermatol. 2014 Feb;134(2):315-8. doi: 10.1038/jid.2013.348. PubMed PMID: 24424456.
2: Berger A, Quast SA, Plötz M, Kuhn NF, Trefzer U, Eberle J. RAF inhibition overcomes resistance to TRAIL-induced apoptosis in melanoma cells. J Invest Dermatol. 2014 Feb;134(2):430-40. doi: 10.1038/jid.2013.347. Epub 2013 Aug 16. PubMed PMID: 23955071.
3: McKay MM, Ritt DA, Morrison DK. RAF inhibitor-induced KSR1/B-RAF binding and its effects on ERK cascade signaling. Curr Biol. 2011 Apr 12;21(7):563-8. doi: 10.1016/j.cub.2011.02.033. Epub 2011 Mar 31. PubMed PMID: 21458265; PubMed Central PMCID: PMC3075323.
4: Takle AK, Bamford MJ, Davies S, Davis RP, Dean DK, Gaiba A, Irving EA, King FD, Naylor A, Parr CA, Ray AM, Reith AD, Smith BB, Staton PC, Steadman JG, Stean TO, Wilson DM. The identification of potent, selective and CNS penetrant furan-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett. 2008 Aug 1;18(15):4373-6. doi: 10.1016/j.bmcl.2008.06.070. Epub 2008 Jun 24. PubMed PMID: 18621524.
5: Shelton JG, Moye PW, Steelman LS, Blalock WL, Lee JT, Franklin RA, McMahon M, McCubrey JA. Differential effects of kinase cascade inhibitors on neoplastic and cytokine-mediated cell proliferation. Leukemia. 2003 Sep;17(9):1765-82. PubMed PMID: 12970777.
