B-Raf inhibitor 1CAS# 1093100-40-3 |
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Quality Control & MSDS
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| Cas No. | 1093100-40-3 | SDF | Download SDF |
| PubChem ID | 44223999 | Appearance | Powder |
| Formula | C26H19ClN8 | M.Wt | 478.94 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : 50 mg/mL (104.40 mM; Need ultrasonic) H2O : < 0.1 mg/mL (insoluble) | ||
| Chemical Name | 1-N-(4-chlorophenyl)-6-methyl-5-N-[3-(7H-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine | ||
| SMILES | CC1=C(C2=C(C=C1)C(=NC=C2)NC3=CC=C(C=C3)Cl)NC4=C(C=CC=N4)C5=C6C(=NC=N5)N=CN6 | ||
| Standard InChIKey | KKVYYGGCHJGEFJ-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C26H19ClN8/c1-15-4-9-19-18(10-12-29-24(19)34-17-7-5-16(27)6-8-17)21(15)35-25-20(3-2-11-28-25)22-23-26(32-13-30-22)33-14-31-23/h2-14H,1H3,(H,28,35)(H,29,34)(H,30,31,32,33) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | B-Raf inhibitor 1 is a potent and selective B-Raf inhibitor with cell IC50s of 0.31 uM and 2 nM for A375 proliferation and A375 p-ERK respectively.
IC50 value: 0.31 uM and 2 nM for A375 proliferation and A375 p-ERK [1]
Target: B-Raf
B-Raf inhibitor 1(Compound 13) binds to and stabilizes B-Raf in a DFG-out, inactive conformation in which the ATP pocket is partially filled by Phe595 and Gly596 from the DFG motif. Compound 13 exhibit low micromolar inhibition against wild type B-Raf cell lines, which may be due to off-target kinase activities or
alternatively to pan-Raf inhibition, including Raf dimers. Compound 13 induced proliferation and hyperplasia in normal tissues of mice [1]. References: | |||||
B-Raf inhibitor 1 Dilution Calculator
B-Raf inhibitor 1 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.0879 mL | 10.4397 mL | 20.8794 mL | 41.7589 mL | 52.1986 mL |
| 5 mM | 0.4176 mL | 2.0879 mL | 4.1759 mL | 8.3518 mL | 10.4397 mL |
| 10 mM | 0.2088 mL | 1.044 mL | 2.0879 mL | 4.1759 mL | 5.2199 mL |
| 50 mM | 0.0418 mL | 0.2088 mL | 0.4176 mL | 0.8352 mL | 1.044 mL |
| 100 mM | 0.0209 mL | 0.1044 mL | 0.2088 mL | 0.4176 mL | 0.522 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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B-Raf inhibitor 1 is a potent and selective B-Raf inhibitor with cell IC50s of 0.31 uM and 2 nM for A375 proliferation and A375 p-ERK respectively.
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Pharmacodynamics of 2-[4-[(1E)-1-(hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-3-(pyridine-4-yl)-1H-pyraz ol-1-yl]ethan-1-ol (GDC-0879), a potent and selective B-Raf kinase inhibitor: understanding relationships between systemic concentrations, phosphorylated mitogen-activated protein kinase kinase 1 inhibition, and efficacy.[Pubmed:19147858]
J Pharmacol Exp Ther. 2009 Apr;329(1):360-7.
The Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase signaling pathway is involved in cellular responses relevant to tumorigenesis, including cell proliferation, invasion, survival, and angiogenesis. 2-[4-[(1E)-1-(Hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-3-(pyridine-4-yl)-1H-pyraz ol-1-yl]ethan-1-ol (GDC-0879) is a novel, potent, and selective B-Raf inhibitor. The objective of this study was to characterize the relationship between GDC-0879 plasma concentrations and tumor growth inhibition in A375 melanoma and Colo205 colon cancer xenografts and to understand the pharmacodynamic (PD) marker response requirements [phosphorylated (p)MEK1 inhibition] associated with tumor growth inhibition in A375 xenografts. Estimates of GDC-0879 plasma concentrations required for tumor stasis obtained from fitting tumor data to indirect response models were comparable, at 4.48 and 3.27 microM for A375 and Colo205 xenografts, respectively. This was consistent with comparable in vitro potency of GDC-0879 in both cell lines. The relationship between GDC-0879 plasma concentrations and pMEK1 inhibition in the tumor was characterized in A375 xenografts after oral doses of 35, 50, and 100 mg/kg. Fitting pMEK1 inhibition to an indirect response model provided an IC(50) estimate of 3.06 microM. pMEK1 inhibition was further linked to A375 tumor volume data from nine different GDC-0879 dosing regimens using an integrated pharmacokinetic-PD model. A simulated PD marker response curve plot of K (rate constant describing tumor growth inhibition) versus pMEK1 inhibition generated using pharmacodynamic parameters estimated from this model, showed a steep pMEK1 inhibition-response curve consistent with an estimated Hill coefficient of approximately equal 8. A threshold of >40% pMEK1 inhibition is required for tumor growth inhibition, and a minimum of approximately 60% pMEK1 inhibition is required for stasis in A375 xenografts treated with GDC-0879.
FOXD3 is a mutant B-RAF-regulated inhibitor of G(1)-S progression in melanoma cells.[Pubmed:20332228]
Cancer Res. 2010 Apr 1;70(7):2891-900.
The forkhead box transcription factor FOXD3 is a stemness factor that prevents the production of melanocyte progenitors from the developing neural crest; however, its role in human cancers is not known. Transformation of melanocytes gives rise to melanoma. In two thirds of melanomas, the serine/threonine kinase B-RAF is mutated to a constitutively active form. Here, we show that FOXD3 levels are upregulated following attenuation of B-RAF and mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK) signaling in mutant B-RAF harboring human melanoma cells. This effect was selective because FOXD3 was not upregulated following MEK inhibition in wild-type B-RAF melanoma cells and mutant B-RAF thyroid carcinoma cells. Ectopic FOXD3 expression potently inhibited melanoma cell growth without altering mutant B-RAF activation of ERK1/2. Inhibition of cell growth was due to a potent G(1) cell cycle arrest and was associated with p53-dependent upregulation of p21(Cip1). FOXD3-induced cell cycle arrest was prevented by p53 depletion and, to a lesser extent, p21(Cip1) depletion. These studies show that FOXD3 is suppressed by B-RAF, uncover a novel role and mechanism for FOXD3 as a negative cell cycle regulator, and have implications for the repression of melanocytic lineage cells.
