118409-58-8 Usage
Description
TYRPHOSTIN A25 is a cell-permeable, reversible, and competitive inhibitor of substrate binding on protein tyrosine kinases. It is a yellow-green powder that inhibits epidermal growth factor receptor tyrosine kinase (IC50 = 3 μM) and the GTPase activity of transducin (IC50 = 7 μM). TYRPHOSTIN A25 also blocks the induction of inducible nitric oxide synthase in glial cells and induces apoptosis in human leukemic cell lines. Additionally, it is reported to inhibit guanylyl cyclase.
Uses
Used in Pharmaceutical Industry:
TYRPHOSTIN A25 is used as an inhibitor of epidermal growth factor receptor tyrosine kinase activity for its ability to inhibit the autophosphorylation of the EGF-receptor with a reported IC50 of 15 μM. This makes it a valuable tool in the development of treatments for various cancers and other diseases related to the overactivity of the epidermal growth factor receptor.
Used in Research Applications:
TYRPHOSTIN A25 is used as a research tool for studying the role of protein tyrosine kinases in cellular processes, such as signal transduction, cell proliferation, and apoptosis. Its ability to inhibit the GTPase activity of transducin and guanylyl cyclase also makes it useful in investigating the functions of these proteins in cellular signaling pathways.
Used in Drug Development:
TYRPHOSTIN A25 is used as a lead compound in the development of new drugs targeting protein tyrosine kinases, which are often overactive in various diseases, including cancer. Its properties as a reversible and competitive inhibitor make it a promising starting point for designing more potent and selective inhibitors for therapeutic use.
Biological Activity
ag-82 is a cell-permeable, reversible, and competitive inhibitor of tyrosine kinase and epidermal growth factor (egf) receptor.protein tyrosine kinases (ptks) have been involved in regulating cell proliferation, cell differentiation, and signaling processes in the immune system. dysfunction of protein tyrosine kinases result in inflammatory responses and diseases including cancer, atherosclerosis, and psoriasis [2]. the epidermal growth factor receptor (egfr) is a transmembrane glycoprotein. activation of egfr results in autophosphorylation of receptor tyrosine kinase and has been involved in regulating cellular proliferation, differentiation, and survival. overexpression of egfr has been identified in a variety of tumor cell lines and has been associated with poor prognosis and decreased survival [3].in the human epidermoid carcinoma cell line a431, ag-82 inhibited the activity of epidermal growth factor receptor kinase with an ic50 value of 3 μm [1]. ag-82 inhibited the gtpase activity of transducin with an ic50 of 7 μm. ag-82 inhibited neuromedin b-induced phosphorylation of p125fak (focal adhesion kinase). ag-82 blocked the induction of inducible nitric oxide synthase in glial cells and induced apoptosis in human leukemic cell lines.
Biochem/physiol Actions
Cell permeable: yes
references
[1] gazit a, yaish p, gilon c, et al. tyrphostins i: synthesis and biological activity of protein tyrosine kinase inhibitors[j]. journal of medicinal chemistry, 1989, 32(10): 2344-2352.[2] levitzki a, gazit a. tyrosine kinase inhibition: an approach to drug development[j]. science, 1995, 267(5205): 1782.[3] herbst r s. review of epidermal growth factor receptor biology[j]. international journal of radiation oncology biology physics, 2004, 59(2): s21-s26.
Check Digit Verification of cas no
The CAS Registry Mumber 118409-58-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,1,8,4,0 and 9 respectively; the second part has 2 digits, 5 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 118409-58:
(8*1)+(7*1)+(6*8)+(5*4)+(4*0)+(3*9)+(2*5)+(1*8)=128
128 % 10 = 8
So 118409-58-8 is a valid CAS Registry Number.
InChI:InChI=1/C10H6N2O3/c11-4-7(5-12)1-6-2-8(13)10(15)9(14)3-6/h1-3,13-15H
118409-58-8Relevant articles and documents
Structural studies on bioactive compounds. 32. Oxidation of tyrphostin protein tyrosine kinase inhibitors with hypervalent iodine reagents
Wells, Geoffrey,Seaton, Angela,Steven, Malcolm F. G.
, p. 1550 - 1562 (2007/10/03)
Hydroxylated styrenes (tyrphostins) undergo oxidation by hypervalent iodine oxidants such as [(diacetoxy)iodo]benzene (DAIB) to give a range of products depending on the structure of the phenolic substrate, the solvent, the oxidant stoichiometry, and the purification strategy. Conditions have been developed to modify the phenolic component of the tyrphostin without affecting the appended substituted-vinyl moiety. Novel products include: unstable 2-acyloxy-2-methoxy-4-(substituted-vinyl)cyclohexadienones and their rearrangement products 2-acyloxy-4-hydroxy-3-methoxy-1-(substituted- vinyl)benzenes; phenyliodoniophenolates and their rearrangement products iodophenoxytyrphostins; and 3,3'-dialkoxy-2,2'-dihydroxy-5,5'-di(substituted- vinyl)biphenyls. None of these oxidation products displayed enhanced activity in vitro in the NCI 60-cell line panel or in a panel of human breast cancer cell lines, compared to their tyrphostin precursors. The inhibitory activity of three representative tyrphostins (3e,n, 28) was not modulated by aerobic/anaerobic conditions in MCF-7 and MDA 468 cells and was independent of EGFR status in clones of ZR75B cells transfected with this receptor. Basal growth of MCF-7 cells was unaffected by co-administration of the growth factors EGF, TGF-α, IGF-I, and IGF-II, and the new agents did not inhibit EGFR and c-erbB2 autophosphorylation in cell lysates from MDA 468 or SkBr3 cells, respectively, suggesting that receptor tyrosine kinases are not targets for these compounds. Growth stimulation by the tyrphostin 3n in the ER+ breast cell lines MCF-7, T47D, and ZR75-1 was abolished by 1 μM tamoxifen, suggesting that this compound has estrogen agonist activity.
Cosmetic composition containing DOPA derivatives
-
, (2008/06/13)
A composition for topical application to human hair or skin contains a chemical analogue of dihydroxyphenyl alanine (DOPA). This chemical analogue can be absorbed by skin or by a hair follicle and metabolised in-vivo, thus leading to the formation of melanin in skin or to the growth of melanin-pigmented hair. Consequently the composition can give controlled skin darkening to mimic sun-induced tanning or can bring about the growth of dar hair in place of the grey or white hair.
Polyhydroxylated phenylacrylic acid derivatives as new anti-tumor agents
Hussoin,FitzGerald,Wick
, p. 416 - 418 (2007/10/02)
Preliminary evidence indicates that antitumor agents containing the o-dihydroxybenzene moiety exhibit enhanced antitumor activity toward malignant cells of high oxidative potential, such as melanoma cells. Based on this consideration, 11 hydroxybenzene acrylic acid derivatives of differing redox potential were prepared as potential substrates for the melanoma specific enzyme tyrosinase, that might exhibit general antitumor activity and enhanced cytotoxicity toward melanoma cells. Five of these compounds [α-cyano-β-(4-hydroxyphenyl)-, α-cyano-β-(3,4-dihydroxyphenyl)-, and α-cyano-β-(3,4,5-trihydroxyphenyl)acrylic acid (THPPA), and 3,4-dihydroxy- and 3,4,5-trihydroxybenzalcyanoacetamide] were found to be substrates for tyrosinase with k(m) values from 0.08 to 4.13 mM and V(max) values from 0.18 to 3.02. These data indicate that as the number of hydroxy groups increases, the rate of oxidation increases, and that cyanoamides were faster reacting than corresponding cyanoacids, with dicyanides the least reactive. In contrast, cyanoamides were less effective as substrates than cyanoacids. In vitro studies showed all but two compounds were active against L1210 (IC50 range 21-980 μM), SK-MEL-28 (IC50 range 54-950 μM), and SK-MEL-30-3 (IC50 range 54-190 μM). Only THPPA was active in vivo against L1210 and B-16 melanoma.
