Home MAPK Raf inhibitor ZM 336372

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ZM 336372 Raf inhibitor

Cat.No.S2720

ZM 336372 (Zinc00581684) is a potent and selective c-Raf inhibitor with IC50 of 70 nM, 10-fold selectivity over B-RAF, no inhibition to PKA/B/C, AMPK, p70S6, etc.
ZM 336372 Raf inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 389.45

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: S272001 DMSO]78 mg/mL]false]Ethanol]2 mg/mL]false]Water]Insoluble]false Purity: 99.09%
99.09

Chemical Information, Storage & Stability

Molecular Weight 389.45 Formula

C23H23N3O3

 Storage (From the date of receipt)
CAS No. 208260-29-1 Download SDF Storage of Stock Solutions

Synonyms Zinc00581684 Smiles CC1=C(C=C(C=C1)NC(=O)C2=CC(=CC=C2)N(C)C)NC(=O)C3=CC=C(C=C3)O

Solubility

In vitro
Batch:

DMSO : 78 mg/mL (200.28 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 2 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Mechanism of Action

Targets/IC50/Ki
C-Raf [1]
70 nM
In vitro
ZM 336372 shows 10-fold selectivity over B-Raf. This compound weakly inhibits SAPK2a/p38α and SAPK2b/p38β with IC50 of 2 μM, and is selective over 17 other protein kinases including PKA, PKC, AMPK, p42 MAPK, MKK1, SAPK1/JNK, and CDK1 even at the concentration of up to 50 μM. It does not prevent constitutive as well as growth factor or phorbol ester induced activation of MKKl or p42 MAPK/ERK2. Moreover, this chemical dose not reverse the phenotype of Ras- or Raf-transformed cell lines. Its treatment induces >100 activation of c-Raf and the B-Raf isoform, but it does not trigger any activation of MKKI or p42 MAPK/ERKP or induce any increase in the GTP-loading of Ras, suggesting that a feedback control loop exists by which Raf isoforms suppress their own activation, such that inhibition is always counterbalanced by reactivation. This compound-induced activation of c-Raf is not prevented by inhibition of the MAPK cascade, protein kinase C or phosphatidylinositide 3-kinase. [1] It (1 μM) abolishes the upregulation of eNOS after treatment with hydrogen peroxide. [2] Its treatment in carcinoid tumor cells results in progressive phosphorylation of Raf-1, mitogen-activated protein kinase 1/2, and extracellular signal-regulated kinase 1/2, and causes a significant reduction of bioactive hormone levels as well as the transcription factor, human achaete-scute homologue-1. Furthermore, this chemical treatment leads to a marked suppression of cellular proliferation and induction of the cell cycle inhibitors p21 and p18. [3] It inhibits the proliferation of pheochromocytoma cells, and suppresses NE vasoactive peptide production. [4] Its treatment in HepG2 induces the suppression of proliferation in a dose-dependent manner, suppression of hormone secretion, and up-regulation of cell cycle inhibitors. [5] It also induces apoptosis in pancreatic adenocarcinoma cell lines by inhibiting glycogen synthase kinase-3β through phosphorylation of GSK-3β at Ser 9. [6]
Kinase Assay
In vitro kinase assay
c-Raf kinase activity is assayed directly in Sl9 cell lysates. Human c-Raf is activated in Sf9 cells by cotransfection from baculovirus vectors containing DNA encoding v-Ras and Lck in the absence of ZM 336372. The cell lysates are then assayed for c-Raf activity in the presence of increasing concentrations of this compound.
References
  • [4] https://pubmed.ncbi.nlm.nih.gov/16603190/
  • [5] https://pubmed.ncbi.nlm.nih.gov/18299943/
  • [6] https://pubmed.ncbi.nlm.nih.gov/20031160/

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