212631-79-3 Usage
Description
PD184352 is a potent and selective inhibitor of the extracellular signal-regulated kinase (ERK) signaling pathway, which is a type of mitogen-activated protein (MAP) kinase. It is an off-white to pale beige solid and is commonly used as a MEK inhibitor, which is an upstream regulator of ERK. By inhibiting the ERK signaling pathway, PD184352 can be utilized in various applications across different industries.
Uses
Used in Pharmaceutical Industry:
PD184352 is used as a pharmaceutical agent for inhibiting the ERK signaling pathway, which plays a crucial role in cell proliferation, differentiation, and survival. Its ability to inhibit this pathway makes it a valuable tool in the development of targeted therapies for various diseases, particularly cancer.
Used in Research and Development:
In the field of research and development, PD184352 is used as a research chemical to study the role of the ERK signaling pathway in cellular processes. It is an essential tool for understanding the molecular mechanisms underlying various diseases and for identifying potential therapeutic targets.
Used in Drug Discovery:
PD184352 is used as a lead compound in drug discovery for the development of novel therapeutics targeting the ERK signaling pathway. Its potent and selective inhibition of MEK makes it a promising starting point for the design and synthesis of new drugs with improved efficacy and safety profiles.
Used in Diagnostics:
PD184352 can be employed as a diagnostic agent to identify the activation status of the ERK signaling pathway in various disease conditions. By measuring the inhibition of this pathway, it can help in the early detection and monitoring of diseases associated with the dysregulation of ERK signaling.
Biological Activity
pd184352 (also known as ci-1040), a benzhydroxamate derivative, is a potent and highly selective mek1/2, two members of the family of mapkks, inhibitor that inhibits purified mek1 with ic50 of 17 nm in a non-atp and non-erk1/2 competitive manner [1].pd184352 binds to a hydrophobic pocket, which is located in a region with low sequence homology to other kinases, adjacent to the mg-atp binding site of mek1 and mek2 inducing a conformational change in un-phosphorylated mek1/2 and hence inactivating the un-phosphorylated mek1/2 [1].pd184352 has been found to be actively against tumors, where it inhibits the growth of colon carcinomas in mouse xenograft models [1].
Biochem/physiol Actions
PD184352 (CI-1040) is a highly selective non-competitive inhibitor of MEK (MKK1; MAPK kinase) and the closely related MKK2. It has anti-cancer activity, suppresses the ERK pathway, and has been used along with other classes of inhibitors to establish embryonic stem cell lines.
references
[1] frémin c, meloche s. from basic research to clinical development of mek1/2 inhibitors for cancer therapy. j hematol oncol. 2010 feb 11;3:8. doi: 10.1186/1756-8722-3-8.
Check Digit Verification of cas no
The CAS Registry Mumber 212631-79-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,1,2,6,3 and 1 respectively; the second part has 2 digits, 7 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 212631-79:
(8*2)+(7*1)+(6*2)+(5*6)+(4*3)+(3*1)+(2*7)+(1*9)=103
103 % 10 = 3
So 212631-79-3 is a valid CAS Registry Number.
InChI:InChI=1/C17H14ClF2IN2O2/c18-12-7-10(21)3-6-14(12)22-16-11(4-5-13(19)15(16)20)17(24)23-25-8-9-1-2-9/h3-7,9,22H,1-2,8H2,(H,23,24)
212631-79-3Relevant articles and documents
Improved experimental procedure for the synthesis of the potent MEK inhibitor PD184352
Shpiro, Natalia,Marquez, Rodolfo
, p. 2265 - 2270 (2005)
An improved synthesis of the potent MEK inhibitor PD184352 (2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzamide)) is herein reported. This new and reproducible protocol provides a simple and efficient way of generating gram quantities of PD184352 with minimal purification. Copyright Taylor & Francis, Inc.
The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901
Barrett, Stephen D.,Bridges, Alexander J.,Dudley, David T.,Saltiel, Alan R.,Fergus, James H.,Flamme, Cathlin M.,Delaney, Amy M.,Kaufman, Michael,LePage, Sophie,Leopold, Wilbur R.,Przybranowski, Sally A.,Sebolt-Leopold, Judith,Van Becelaere, Keri,Doherty, Annette M.,Kennedy, Robert M.,Marston, Dan,Howard Jr., W. Allen,Smith, Yvonne,Warmus, Joseph S.,Tecle, Haile
supporting information; experimental part, p. 6501 - 6504 (2009/10/01)
A novel series of benzhydroxamate esters derived from their precursor anthranilic acids have been prepared and have been identified as potent MEK inhibitors. 2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzam ide, CI-1040, was the first MEK inhibitor to demonstrate in vivo activity in preclinical animal models and subsequently became the first MEK inhibitor to enter clinical trial. CI-1040 suffered however from poor exposure due to its poor solubility and rapid clearance, and as a result, development of the compound was terminated. Optimization of the diphenylamine core and modification of the hydroxamate side chain for cell potency, solubility, and exposure with oral delivery resulted in the discovery of the clinical candidate N-(2,3-dihydroxy-propoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-b enzamide PD 0325901.
4-bromo or 4-iodo phenylamino benzhydroxamic acid derivatives and their use as MEK inhibitors
-
, (2008/06/13)
Phenylamino benzhydroxamic acid derivatives of formula (I) where R1, R2, R3, R4, R5, and R6 are hydrogen or substituent groups such as alkyl, and where R7 is hydrogen or an organic radical, are potent inhibitors of MEK and, as such, are effective in treat
