1276121-88-0

Basic information

• Product Name: PF 3644022
• Synonyms: PF 3644022;(10R)-9,10,11,12-Tetrahydro-10-Methyl-3-(6-Methyl-3-pyridinyl)-8H-[1,4]diazepino[5',6':4,5]thieno[3,2-f]quinolin-8-one;MK2 INHIBITOR
• CAS NO: 1276121-88-0
• Molecular Formula: C21H18N4OS
• Molecular Weight: 374.45882
• Product Categories: Aromatics;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 1276121-88-0.mol
• Article Data: 0

Chemical Properties

• Appearance: /
• Storage Temp.: 2-8°C(protect from light)
• Solubility: DMSO (Slightly), Methanol (Slightly)
• CAS DataBase Reference: PF 3644022(CAS DataBase Reference)
• NIST Chemistry Reference: PF 3644022(1276121-88-0)
• EPA Substance Registry System: PF 3644022(1276121-88-0)

Safety Data

• Hazardous Substances Data: 1276121-88-0(Hazardous Substances Data)

Usage

Description

PF 3644022, also known as a benzothiophene inhibitor, is a potent and freely reversible ATP-competitive compound that specifically inhibits mitogen-activated protein kinase-activated protein kinase 2 (MK2) with high affinity (Ki = 3 nM) and selectivity. It has been profiled against 200 human kinases, demonstrating its specificity for MK2 inhibition. PF 3644022 has shown significant anti-inflammatory and anticancer properties, making it a promising candidate for various therapeutic applications.

Uses

Used in Pharmaceutical Industry:
PF 3644022 is used as an anti-inflammatory agent for its ability to inhibit tumor necrosis factor α (TNF-α) production. This inhibition helps in reducing inflammation and alleviating symptoms associated with acute and chronic inflammatory conditions.
Used in Oncology:
PF 3644022 is used as an anticancer agent, targeting the MK2 pathway, which plays a crucial role in tumor growth and progression. By inhibiting MK2 activity, PF 3644022 can potentially suppress the growth of cancer cells and enhance the effectiveness of conventional cancer therapies.
Used in Drug Development:
PF 3644022 serves as a valuable tool in drug development, particularly in the discovery and optimization of novel MK2 inhibitors. Its high selectivity and potency make it an ideal starting point for the design of new compounds with improved pharmacological properties and therapeutic potential.

Biological Activity

pf-3644022 is a potent and selective mitogen-activated protein kinase (mapk)-activated protein kinase-2 (mk2) inhibitor (ki =3 nm). [1]pf-3644022 is the first oral mk2 inhibitor in both acute and chronic models of inflammation. pf-3644022 reversibly atp-competitive inhibits mk2 enzyme activity with good selectivity across 200 human kinases. [1]in the human u937 monocytic cell line or peripheral blood mononuclear cells, pf-3644022 potently inhibits tnf production with ic50 value of 160 nm. in lps-stimulated human whole blood, pf-3644022 blocks tnf and il-6 production with ic50 values of 1.6 and 10.3 μm, respectively. in u937 cells and blood, inhibition of tnf correlates closely with inhibition of phospho-heat shock protein 27, a target biomarker of mk2 activity. [1]in the rat lps-induced tnf model, pf-3644022 efficacy in the chronic inflammation model is strongly correlated with maintaining a cmin higher than the ec50 measured. pf-3644022 exhibits efficaciously oral activity and good pharmacokinetic parameters in both the chronic streptococcal cell wall-induced arthritis model and the rat acute lps-induced tnf model. [1]

references

1. mourey rj, burnette bl, brustkern sj et al. a benzothiophene inhibitor of mitogen-activated protein kinase-activated protein kinase 2 inhibits tumor necrosis factor alpha production and has oral anti-inflammatory efficacy in acute and chronic models of inflammation. j pharmacol exp ther. 2010 jun;333(3):797-807. doi: 10.1124/jpet.110.166173. epub 2010 mar 17.