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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Purity: ≥98%
ZM 336372 (ZM-336372; ZM336372) is a novel, potent and selective c-Raf kinase inhibitor with potential anticancer activity. It exhibits 10-fold greater selectivity for c-RAF over B-RAF and inhibits c-Raf with an IC50 of 70 nM. Other kinases aren't inhibited by it at all. When compared to the known C-Raf inhibitor PD98059, ZM336372 has a different selectivity. By preventing C-Raf activation, ZM3363372 treatment reduced the percentage of low potassium-induced apoptosis in primary neurons. Pretreatment with H2O2 and ZM336372 for 24 hours completely reversed the ROS-induced eNOS up-regulation in tumor spheroids by mediating the ERK1/2 signaling pathway.
Targets |
c-Raf (IC50 = 0.07 μM)
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ln Vitro |
ZM 336372 shows 10-fold selectivity over B-Raf. ZM 336372 selectively inhibits 17 other protein kinases, including PKA, PKC, AMPK, p42 MAPK, MKK1, SAPK1/JNK, and CDK1, even at concentrations as high as 50 μM.It weakly inhibits SAPK2a/p38α and SAPK2b/p38β with an IC50 of 2 μM. ZM 336372 does not stop the activation of MKKl or p42 MAPK/ERK2 that is caused by constitutive, growth factor, or phorbol ester induction. Additionally, ZM 336372 does not change the phenotype of cell lines with Ras- or Raf-transformed. ZM 336372 treatment causes >100 activation of c-Raf and the B-Raf isoform but no activation of MKKI, p42 MAPK/ERKP, or any increase in the GTP-loading of Ras, indicating the existence of a feedback control loop by which Raf isoforms suppress their own activation, such that inhibition is always counterbalanced by reactivation. Inhibiting the MAPK cascade, protein kinase C, or phosphatidylinositide 3-kinase does not stop ZM 336372-induced activation of c-Raf. [1] After exposure to hydrogen peroxide, eNOS upregulation is eliminated by ZM 336372 (1 M).[2] In carcinoid tumor cells, treatment with ZM 336372 causes Raf-1, mitogen-activated protein kinase 1/2, and extracellular signal-regulated kinase 1/2 to become increasingly phosphorylated. It also significantly lowers levels of bioactive hormones and the transcription factor human achaete-scute homologue-1. Additionally, ZM 336372 treatment results in the induction of the cell cycle inhibitors p21 and p18 as well as a notable suppression of cellular proliferation. [3] Pheochromocytoma cell proliferation is inhibited by ZM 336372, and NE vasoactive peptide production is suppressed.[4] Treatment with ZM 336372 in HepG2 results in the up-regulation of cell cycle inhibitors, a dose-dependent suppression of proliferation, and a suppression of hormone secretion.[5] By blocking glycogen synthase kinase-3β and phosphorylating GSK-3β at Ser 9, ZM 336372 also causes apoptosis in pancreatic adenocarcinoma cell lines. [6]
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ln Vivo |
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Enzyme Assay |
Sl9 cell lysates are used to directly measure the activity of c-Raf kinase. In the absence of ZM 336372, cotransfection of baculovirus vectors containing DNA encoding v-Ras and Lck activates human c-Raf in Sf9 cells. Then, with increasing concentrations of ZM 336372, the cell lysates are tested for c-Raf activity.
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Cell Assay |
ZM 336372 is applied to cells at different concentrations for 48 and 72 hours. Cells are trypsinized after the medium has been removed from the incubation. Prior to flow cytometry, cells are incubated on ice for 5 minutes and 2.5 g/mL propidium iodide is added. CellQuest acquisition and analysis software is used to collect data using a FACSCalibur benchtop flow cytometer. Cell Titer Glo Assay is used to measure cytotoxicity. Using the MTT assay, cell proliferation is measured.
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Animal Protocol |
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References |
Molecular Formula |
C23H23N3O3
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Molecular Weight |
389.45
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Exact Mass |
389.17
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Elemental Analysis |
C, 70.93; H, 5.95; N, 10.79; O, 12.32
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CAS # |
208260-29-1
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Related CAS # |
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Appearance |
Solid powder
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SMILES |
CC1=C(C=C(C=C1)NC(=O)C2=CC(=CC=C2)N(C)C)NC(=O)C3=CC=C(C=C3)O
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InChi Key |
PYEFPDQFAZNXLI-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C23H23N3O3/c1-15-7-10-18(24-23(29)17-5-4-6-19(13-17)26(2)3)14-21(15)25-22(28)16-8-11-20(27)12-9-16/h4-14,27H,1-3H3,(H,24,29)(H,25,28)
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Chemical Name |
3-(Dimethylamino)- N -[3-[(4-hydroxybenzoyl)-amino]-4-methylphenyl]benzamide
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Synonyms |
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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 |
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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) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (6.42 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 ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.5677 mL | 12.8386 mL | 25.6772 mL | |
5 mM | 0.5135 mL | 2.5677 mL | 5.1354 mL | |
10 mM | 0.2568 mL | 1.2839 mL | 2.5677 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.
MTT assay of pancreatic adenocarcinoma cells treated with ZM336372 every other day for 8 days. J Surg Res . 2010 Jun 1;161(1):28-32. td> |
Mia PaCa-2 (A.) and Panc-1 (B.) cells treated with ZM336372 for 2 days were extracted. J Surg Res . 2010 Jun 1;161(1):28-32. td> |
Chemical structure of ZM336372. ZM336372′s chemical name is N-[5-(dimethyl-aminobensamido)-2-methylphenyl]-4-hydroxybenzamide. Mol Cancer Ther . 2005 Jun;4(6):910-7. td> |
Western analysis for Raf-1 pathway activation in response to ZM336372 treatment. Mol Cancer Ther . 2005 Jun;4(6):910-7. td> |
Western analysis of ZM336372 effect upon chromogranin A (CgA) and hASH1. Mol Cancer Ther . 2005 Jun;4(6):910-7. td> |
Cell proliferation analysis of ZM336372. Mol Cancer Ther . 2005 Jun;4(6):910-7. td> |
Cellular toxicity analysis of ZM336372. Mol Cancer Ther . 2005 Jun;4(6):910-7. td> |