Background[1-3]
Protein phosphatase-1B antibody is a type of polyclonal antibody that can specifically bind to protein phosphatase-1B. It is mainly used for Western Blot, IHC-P, IF, ELISA, etc. to detect protein phosphatase-1B. Co-IP and other immunological experiments.
The English name of protein phosphatase-1 (antigen) is PP1, which is a chemical substance with the chemical formula C16H21N5 and a molecular weight of 283.37144.
PP1 is a nanomolar inhibitor of Lck and FynT. It acts on T cells and inhibits the protein-tyrosine kinase activity induced by anti-CD3. The IC50 is 0.5μM. It acts on Lck and FynT more selectively than ZAP. -70 is high, and PP1 preferentially inhibits T cell receptor-dependent anti-CD3-induced T cell proliferation compared with T cell-independent 12-myristate-13-phorbol acetate/IL-2-induced T cell proliferation. T cell proliferation (IC50 is 0.5 μM).
PP1 (1μM) selectively inhibits the induction of IL-2 gene but not granulocyte-macrophage colony-stimulating factor or IL-2 receptor gene. PP1 also inhibits Src (IC50, 170 nM) and Hck (IC50, 20 nM). PP1 bactericidal preservative is 50-100 times less effective at inhibiting A-431 epidermal growth factor receptor autophosphorylation (IC50 of 0.25 μM).
PP1 also inhibits Kit and Bcr-Abl tyrosine kinases with IC50 of ∼75 nM and 1 μM, respectively. PP1 completely abolishes M07e cell proliferation in response to SCF with an IC50 of 0.5–1 μM. PP1 (1μM) acts on intact cells, inhibits SCF-induced c-Kit autophosphorylation, and inhibits the activation of MAPK and Akt.
PP1 inhibits the activity of constitutively mutated activating forms of c-Kit found in mast cell diseases (D814V and D814Y) in the rat basophilic leukemia cell line RBL-2H3 expressing mutant c-Kit. Trigger apoptosis. PP1 acts on FDCP1 cells expressing Bcr-Abl, reducing the signal transduction and activation of transcription factor 5 and MAPK, and promoting apoptosis.
Apply[4][5]
For the design, synthesis and biological activity research of new protein tyrosine phosphatase 1B inhibitors
Protein tyrosine phosphatase 1B (PTPIB) is a negative regulator of the insulin and leptin signaling pathways. PTP1B gene knockout and antisense nucleotide treatment experiments in mice indicate that PTP1B is a potential target for the treatment of diabetes and obesity. Therefore, small molecule PTP1B inhibitors may become a new way to treat type 2 diabetes and obesity.
In recent years, using design methods based on the three-dimensional structure of PTP1B enzyme, a large number of efficient and highly selective small molecule inhibitors have been discovered, and the inhibitory activity of many compounds against PTP1B has reached the nanomolar level. However, it is regrettable that these compounds themselves have a high negative charge and mainly exist in the form of negative ions in the organism, which is not conducive to permeation of the cell membrane, resulting in poor bioavailability; some inhibitors have different selectivities for different PTPases. Not good, it is not conducive to effective action on specific PTPase targets.
These factors limit their development into therapeutically valuable drugs. Finding a balance between effectiveness, specificity and pharmaceutical properties is a huge challenge in the research and development of small molecule PTP1B inhibitors as oral anti-diabetic drugs.
Design, synthesize and screen out specific PTP1B inhibitors with high efficiency and good cell membrane permeability. The main research results are as follows: (Utilizing a method based on structure design, using the substrate tyrosine phosphate as a template: replacing the benzene ring with a naphthalene ring; replacing the phosphate part of the substrate with carboxylic acid to simulate its catalytic site with the enzyme Combine;
At the same time, a hydrophobic group was introduced to combine with the area around the catalytic site through hydrophobic interaction, and three series of naphthylalanine derivatives and analogues were designed and synthesized. Activity studies show that these compounds are a type of highly efficient and competitive PTP1B inhibitors that can compete with the substrate for the enzyme’s binding site;
It has good selectivity for other PTPases. Comparing PTP1B and TCPTP, 77a, 79h and 810 dipropylene glycol butyl ether showed 3 times, 6 times and 7 times the selectivity respectively. At the same time, these compounds have obvious inhibitory effects on CDC25B.
