174678-80-9Relevant academic research and scientific papers
Rational design of selective organoruthenium inhibitors of protein tyrosine phosphatase 1B
Ong, Jun Xiang,Yap, Chun Wei,Ang, Wee Han
, p. 12483 - 12492 (2013/01/15)
Protein tyrosine phosphatases (PTPs) belong to a large family of important regulatory enzymes involved in vital mammalian signaling pathways. Selective inhibitors of PTPs are highly valuable from a therapeutic standpoint given their association with various pathological conditions. One such target is PTP-1B which has previously been linked to diabetes and cancer. However, developing a selective inhibitor against PTP-1B has proven to be daunting because the enzyme shares a high degree of structural homology with TC-PTP, an essential PTP involved in modulating immune functions. To address this challenge, a series of organoruthenium complexes was developed to bind at the PTP substrate-binding site while simultaneously target the peripheral structural space. By capitalizing on the potential difference in the structural environment proximal to the active site between different PTPs, selectivity toward PTP-1B over TC-PTP was improved, paving the way for organoruthenium complexes as selective PTP-1B metalloinhibitors.
Discovery and structure-activity relationships of novel sulfonamides as potent PTP1B inhibitors
Holmes, Christopher P.,Li, Xianfeng,Pan, Yijun,Xu, Caiding,Bhandari, Ashok,Moody, Claire M.,Miguel, Joy A.,Ferla, Steven W.,De Francisco, M. Nuria,Frederick, Brian T.,Zhou, Siqun,Macher, Natalie,Jang, Larry,Irvine, Jennifer D.,Grove, J. Russell
, p. 4336 - 4341 (2007/10/03)
A series of novel sulfonamides containing a single difluoromethylene- phosphonate group were discovered to be potent inhibitors of protein tyrosine phosphatase 1B. Structure-activity relationships around the scaffold were investigated, leading to the identification of compounds with IC50 or Ki values in the low nanomolar range. These sulfonamide-based inhibitors exhibit 100 and 30 times higher inhibitory activity than the corresponding tertiary amines and carboxamides, respectively.
Structure of protein tyrosine phosphatase 1B in complex with inhibitors bearing two phosphotyrosine mimetics
Jia,Ye,Dinaut,Wang,Waddleton,Payette,Ramachandran,Kennedy,Hum,Taylor
, p. 4584 - 4594 (2007/10/03)
Protein tyrosine phosphatases (PTPases) are signal-transducing enzymes that dephosphorylate intracellular proteins that have phosphorylated tyrosine residues. It has been demonstrated that protein tyrosine phosphatase 1B (PTP1B) is an attractive therapeut
Enzymatic desymmetrization of prochiral 2-benzyl-1,3-propanediol derivatives: A practical chemoenzymatic synthesis of novel phosphorylated tyrosine analogues
Yokomatsu, Tsutomu,Minowa, Takayuki,Murano, Tetsuo,Shibuya, Shiroshi
, p. 9341 - 9356 (2007/10/03)
(Phosphonomethyl)phenylalanine (Pmp) and (phosphonodifluoromethyl)phenylalanine (F2Pmp) as well as their β-amino acid congeners were prepared as a protecting variant amenable to the peptide synthesis from readily available 2-benzyl-1,3-propandiols possessing either a diethylphosphonomethyl- or diethylphosphonodifluoromethyl functionality at the para-position via the lipase-catalyzed desymmetrization.
Synthesis of L-2,3,5,6-tetrafluoro-4-(phosphonomethyl)phenylalanine, a novel non-hydrolyzable phosphotyrosine mimetic and L-4-(phosphonodifluoromethyl)phenylalanine
Liu, Wang-Qing,Roques, Bernard P.,Garbay, Christiane
, p. 1389 - 1392 (2007/10/03)
A new non-hydrolyzable phosphotyrosine analogue, L-F4Pmp and its N-Fmoc protected derivative were prepared by using an enantioselective synthetic pathway with camphor sultam as chiral auxiliary. The side chain pKa2 (6.9) of L-F4
