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Wyświetlanie 1-15 z 37
Tytuł:
Design, synthesis and biological evaluation of some novel substituted quinazoline derivatives as antitumor agents.
Autorzy:
Ahmed, Marwa
Magdy, Naja
Powiązania:
https://bibliotekanauki.pl/articles/895417.pdf
Data publikacji:
2018-06-30
Wydawca:
Polskie Towarzystwo Farmaceutyczne
Tematy:
cytotoxicity
quinazoline
Tyrosine kinases
Opis:
New series of 6,8-dibromo-2-(4-chlorophenyl)quinazolin-4-yloxy derivatives were synthesized and their cytotoxic activity on MCF7, HEPG2 and HCT116 cell lines were evaluated. Compound XI and XIIIb were two times more active than doxorubicin on MCF7 cancer cell line. Compound VIIIa was 3 times more active than doxorubicin on HEPG2 cancer cell line. While compounds XII, XIIIa and XIIIb were more potent than doxorubicin on HCT116 cancer cell line. IC50 of all newly synthesized compounds were evaluated in vitro for thier inhibition to EGFR tyrosine kinase. All compound show good inhibitory activity on EGFR tyrosine kinase with IC50 range (6.19-19.87) µM.
Źródło:
Acta Poloniae Pharmaceutica - Drug Research; 2018, 75, 3
0001-6837
2353-5288
Pojawia się w:
Acta Poloniae Pharmaceutica - Drug Research
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Activity of selected aromatic amino acids in biological systems
Autorzy:
Krzyściak, Wirginia
Powiązania:
https://bibliotekanauki.pl/articles/1039824.pdf
Data publikacji:
2011
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
tyrosine
reactive oxygen species
kynurenic acid
Opis:
Besides the structural function in proteins, aromatic amino acids are precursors of many important biological compounds essential for normal functioning of the human organism. Many of these compounds may be used as markers for identification of specific pathological states. Comprehensive knowledge about the metabolism of aromatic amino acids and mechanisms of action of their metabolites made it possible to develop effective treatments for many disorders. However, it should not be forgotten that in some pathological conditions, these compounds could not only be involved in the pathogenesis of many disease entities but could also be used as an important tool in prediction of many diseases. This paper contains a review of published literature on aromatic amino acids in the context of physiological processes of the human body and chosen social disorders, such as cancers; psychiatric disorders: depression, anxiety states, schizophrenia, bipolar affective disorders; neurodegenerative, and cardiovascular diseases; chronic kidney insufficiency or diabetes.
Źródło:
Acta Biochimica Polonica; 2011, 58, 4; 461-466
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Regulatory mechanisms for the expression and activity of platelet-derived growth factor receptor.
Autorzy:
Funa, Keiko
Uramoto, Hidetaka
Powiązania:
https://bibliotekanauki.pl/articles/1043436.pdf
Data publikacji:
2003
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
review
tyrosine kinase
expression
receptor
PDGF
Opis:
PDGF is one of the most potent serum mitogens, and the signalling mechanism by way of its receptor tyrosine-kinase has been extensively studied since its first purification in 1979. The identification of homology between the simian sarcoma virus oncogene, v-sis, and the B-chain of PDGF, as well as the frequent over-expression of both the ligands and receptors in various tumours and stroma led to the proposal of the PDGF-mediated autocrine and paracrine hypothesis. Consistent with the important roles of PDGF in the growth and survival of cells, the expression and activity of PDGF receptors are tightly controlled by both positive and negative feedback mechanisms at different levels. The deregulation of the control system can result in serious pathological conditions such as chronic inflammation and tumours. Understanding the molecular mechanisms for the regulatory system and the signalling pathway of PDGF is essential in order to find effective therapies in the diseases where PDGF is involved.
Źródło:
Acta Biochimica Polonica; 2003, 50, 3; 647-658
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Chlorination of N-acetyltyrosine with HOCl, chloramines, and myeloperoxidase-hydrogen peroxide-chloride system
Autorzy:
Drabik, Grażyna
Naskalski, Jerzy
Powiązania:
https://bibliotekanauki.pl/articles/1044197.pdf
Data publikacji:
2001
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
chlorination
hypochlorite
N-acetyltyrosine
tyrosine chloroderivatives
Opis:
N-acetyl-L-tyrosine (N-acTyr), with the alpha amine residue blocked by acetylation, can mimic the reactivity of exposed tyrosyl residues incorporated into polypeptides. In this study chlorination of N-acTyr residue at positions 3 and 5 in reactions with NaOCl, chloramines and the myeloperoxidase (MPO)-H2O2-Cl- chlorinating system were invesigated. The reaction of N-acTyr with HOCl/OCl- depends on the reactant concentration ratio employed. At the OCl-/N-acTyr (molar) ratio 1:4 and pH 5.0 the chlorination reaction yield is about 96% and 3-chlorotyrosine is the predominant reaction product. At the OCl-/ N-acTyr molar ratio 1:1.1 both 3-chlorotyrosine and 3,5-dichlorotyrosine are formed. The yield of tyrosine chlorination depends also on pH, amounting to 100% at pH 5.5, 91% at pH 4.5 and 66% at pH 3.0. Replacing HOCl/OCl- by leucine/chloramine or alanine/chloramine in the reaction system, at pH 4.5 and 7.4, produces trace amount of 3-chlorotyrosine with the reaction yield of about 2% only. Employing the MPO-H2O2-Cl- chlorinating system at pH 5.4, production of a small amount of N-acTyr 3-chloroderivative was observed, but the reaction yield was low due to the rapid inactivation of MPO in the reaction system. The study results indicate that direct chlorination of tyrosyl residues which are not incorporated into the polypeptide structure occurs with excess HOCl/OCl- in acidic media. Due to the inability of the myeloperoxidase-H2O2-Cl- system to produce high enough HOCl concentrations, the MPO-mediated tyrosyl residue chlorination is not effective. Semistable amino-acid chloramines also appeared not effective as chlorine donors in direct tyrosyl chlorination.
Źródło:
Acta Biochimica Polonica; 2001, 48, 1; 271-275
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Characterization of dual specificity protein kinase from maize seedlings.
Autorzy:
Trojanek, Joanna
Klimecka, Maria
Fraser, Anna
Dobrowolska, Grażyna
Muszyńska, Grażyna
Powiązania:
https://bibliotekanauki.pl/articles/1041540.pdf
Data publikacji:
2004
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
dual specificity kinase
tyrosine phosphorylation
maize
Opis:
A protein kinase of 57 kDa, able to phosphorylate tyrosine in synthetic substrates pol(Glu4,Tyr1) and a fragment of Src tyrosine kinase, was isolated and partly purified from maize seedlings (Zea mays). The protein kinase was able to phosphorylate exogenous proteins: enolase, caseins, histones and myelin basic protein. Amino acid analysis of phosphorylated casein and enolase, as well as of phosphorylated endogenous proteins, showed that both Tyr and Ser residues were phosphorylated. Phosphotyrosine was also immunodetected in the 57 kDa protein fraction. In the protein fraction there are present 57 kDa protein kinase and enolase. This co-purification suggests that enolase can be an endogenous substrate of the kinase. The two proteins could be resolved by two-dimensional electrophoresis. Specific inhibitors of typical protein-tyrosine kinases had essentially no effect on the activity of the maize enzyme. Staurosporine, a nonspecific inhibitor of protein kinases, effectively inhibited the 57 kDa protein kinase. Also, poly L-lysine and heparin inhibited tyrosine phosphorylation by 57 kDa maize protein kinase. The substrate and inhibitor specificities of the 57 kDa maize protein kinase phosphorylating tyrosine indicate that it is a novel plant dual-specificity protein kinase.
Źródło:
Acta Biochimica Polonica; 2004, 51, 3; 635-647
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Synthesis of ring labeled [1-14C]-L-tyrosine
Autorzy:
Kański, R.
Augustyniak, W.
Kańska, M.
Powiązania:
https://bibliotekanauki.pl/articles/148523.pdf
Data publikacji:
2006
Wydawca:
Instytut Chemii i Techniki Jądrowej
Tematy:
carbon-14
labeling
tyrosine
enzyme
optical isotopomer
Opis:
The synthesis of specifically ring labeled isotopomer of L-tyrosine, (l-Tyr), using chemical and enzymatic methods is reported. The carbon-14 labeled [1’-14C]-L-Tyr has been synthesized by a 6-step conversion of [2-14C]-malonic acid into [4’-14C]-phenol and its subsequent condensation with S-methyl-L-cysteine using enzyme tyrosine phenol lyase from Citrobacter freundii.
Źródło:
Nukleonika; 2006, 51,suppl.2; 13-16
0029-5922
1508-5791
Pojawia się w:
Nukleonika
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Enzymatic reductive amination of p-hydroxy- and phenylpyruvic acids as a method of synthesis of L-tyrosine and L-phenylalanine labelled with deuterium and tritium
Autorzy:
Pałka, K.
Kańska, M.
Powiązania:
https://bibliotekanauki.pl/articles/146609.pdf
Data publikacji:
2012
Wydawca:
Instytut Chemii i Techniki Jądrowej
Tematy:
deuterium
enzyme
L-phenylalanine
tritium
L-tyrosine
Opis:
We report the synthesis of isotopomers of L-phenylalanine and L-tyrosine selectively labelled with hydrogen isotopes in the 2-position of the side chain. The deuterium or tritium label was introduced using reductive amination activity of enzyme L-phenylalanine dehydrogenase (EC 1.4.1.20). This way p-phenylpyruvic acid was converted into [2-2H]-, [2-3H]-, and doubly labelled [2-2H/3H]-isotopomers of L-phenylalanine, using deuteriated, tritiated, and mixed (DTO) incubation media, respectively. Similarly, p-hydroxyphenylpyruvic acid was converted into [2-2H]-, [2-3H]-, and [2-2H/3H]-L-tyrosine. Deuterium labelled isotopomers of L-phenylalanine and --tyrosine can be used as markers in the investigation of abnormal metabolism of these amino acids observed in patients with inborn genetic diseases such as phenylketonuria and tyrosinemia.
Źródło:
Nukleonika; 2012, 57, 3; 383-387
0029-5922
1508-5791
Pojawia się w:
Nukleonika
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
The effect of tyrosine kinase inhibitors used in the treatment of chronic myeloid leukemia on the cardiovascular system
Autorzy:
Sacha, Tomasz
Góra-Tybor, Joanna
Szmit, Sebastian
Powiązania:
https://bibliotekanauki.pl/articles/1035757.pdf
Data publikacji:
2019
Wydawca:
Medical Education
Tematy:
cardiovascular toxicity
chronic myeloid leukemia
tyrosine kinase inhibitors
Opis:
The use of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia has significantly improved the prognosis and outcomes for most patients. Clinical trials indicate that long-term CML therapy requires the introduction of second- or third-generation inhibitors in approximately 40–50% of cases. Effective in the case of imatinib resistance or intolerance, second generation TKI’s can also be used as a first-line treatment, leading to a faster, and deeper molecular response. TKIs, however, have also been observed to cause significant late adverse effects, including cardiovascular complications, which may raise certain safety concerns. The excellent treatment outcomes achieved with tyrosine kinase inhibitors have led to a gradual increase in the number and age of treated patients, and the associated higher incidence and severity of age-related co-morbidities such as diabetes, hypercholesterolemia, atherosclerosis, ischemic heart disease, hypertension, and congestive heart failure, which raise the risk of treatment-related cardiovascular complications. The article discusses the effects of individual TKIs on the pathogenesis of cardiovascular complications and presents the results of clinical trials that studied their impact on the incidence of such events.
Źródło:
OncoReview; 2019, 9, 1; 3-21
2450-6125
Pojawia się w:
OncoReview
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Patient with metastatic renal cell carcinoma treated successfully with pazopanib for four years.
Autorzy:
Słowik, Agnieszka
Streb, Joanna
Chrzan, Robert
Krzemieniecki, Krzysztof
Powiązania:
https://bibliotekanauki.pl/articles/1065279.pdf
Data publikacji:
2015
Wydawca:
Medical Education
Tematy:
metastatic renal cell carcinoma
pazopanib
tyrosine kinase inhibitors
Opis:
We present a case of a patient with metastatic renal cell carcinoma who was treated with pazopanib in the first-line treatment. Although nephrectomy was not performed, there was a positive reaction to the therapy with multi-targeted tyrosine kinase inhibitor. After 18 months of the palliative treatment, the cancerous kidney was surgically removed and pazopanib was restarted with the effect of further disease remission. The development of hypertension, complete hair discoloration and isolated hyperbilirubinemia occurred, and there was occasionally hypokalaemia in laboratory findings within 48 months of therapy. No serious adverse events were reported.
Źródło:
OncoReview; 2015, 5, 3; A109-116
2450-6125
Pojawia się w:
OncoReview
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
A Fluorescence, 1H NMR spectroscopy and molecular dynamics study of the influence of rotamer population on fluorescence decay of tyrosine, phenylalanine and their derivatives
Autorzy:
Ganzynkowicz, R.
Liwo, A.
Wiczk, W.
Powiązania:
https://bibliotekanauki.pl/articles/1965825.pdf
Data publikacji:
2001
Wydawca:
Politechnika Gdańska
Tematy:
tyrosine
phenylalanine
rotamers
fluorescence
molecular dynamics
NMR spectroscopy
Opis:
Molecular dynamics simulations were carried out on tyrosine and phenylalanine and their derivatives with various terminal groups to determine the populations of side-chain rotamers. The obtained populations were compared with those calculated from fluorescence-decay lifetime distributions and NMR studies. It was found that theoretically calculated populations do not match the experimental ones, which suggests that the static rotamer model is inadequate to explain the dynamics of tyrosine and phenylalanine side chain in fluorescence and NMR experiments.
Źródło:
TASK Quarterly. Scientific Bulletin of Academic Computer Centre in Gdansk; 2001, 5, 3; 311-316
1428-6394
Pojawia się w:
TASK Quarterly. Scientific Bulletin of Academic Computer Centre in Gdansk
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
High sequence homology between protein tyrosine acid phosphatase from boar seminal vesicles and human prostatic acid phosphatase
Autorzy:
Wysocki, Paweł
Płucienniczak, Grażyna
Strzeżek, Jerzy
Powiązania:
https://bibliotekanauki.pl/articles/1040544.pdf
Data publikacji:
2009
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
phosphorylation
boar
protein tyrosine phosphatase
seminal plasma
prostatic acid phosphatase
Opis:
Boar seminal vesicle protein tyrosine acid phosphatase (PTAP) and human prostatic acid phosphatase (PAP) show high affinity for protein phosphotyrosine residues. The physico-chemical and kinetic properties of the boar and human enzymes are different. The main objective of this study was to establish the nucleotide sequence of cDNA encoding boar PTAP and compare it with that of human PAP cDNA. Also, the amino-acid sequence of boar PTAP was compared with the sequence of human PAP. PTAP was isolated from boar seminal vesicle fluid and sequenced. cDNA to boar seminal vesicle RNA was synthesized, amplified by PCR, cloned in E. coli and sequenced. The obtained N-terminal amino-acid sequence of boar PTAP showed 92% identity with the N-terminal amino-acid sequence of human PAP. The determined sequence of a 354 bp nucleotide fragment (GenBank accession number: GQ184596) showed 90% identity with the corresponding sequence of human PAP. On the basis of this sequence a 118 amino acid fragment of boar PTAP was predicted. This fragment showed 89% identity with the corresponding fragment of human PAP and had a similar hydropathy profile. The compared sequences differ in terms of their isoelectric points and amino-acid composition. This may explain the differences in substrate specificity and inhibitor resistance of boar PTAP and human PAP.
Źródło:
Acta Biochimica Polonica; 2009, 56, 3; 481-486
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
The 35 kDa acid metallophosphatase of the frog Rana esculenta liver: studies on its cellular localization and protein phosphatase activity.
Autorzy:
Szalewicz, Agata
Strzelczyk, Barbara
Sopel, Mirosław
Kubicz, Aleksandra
Powiązania:
https://bibliotekanauki.pl/articles/1043638.pdf
Data publikacji:
2003
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
metallophosphatase
acid phosphatase
frog liver
protein phosphatase
tyrosine protein phosphatase
Opis:
The cellular localization of the 35 kDa, low molecular mass acid metallophosphatase (LMW AcPase) from the frog (Rana esculenta) liver and its activity towards P-Ser and P-Tyr phosphorylated peptides were studied. This enzyme was localized to the cytoplasm of hepatocytes but did not appear in other cells of liver tissue (endothelium, macrophages, blood cells). This LMW AcPase does not display activity towards 32P-phosphorylase a under conditions standard for the enzymes of PPP family. Proteins containing P-Ser: rabbit 32P-phosphorylase a and phosvitin are hydrolysed only at acidic pH and are poor substrates for this enzyme. The frog AcPase is not inhibited by okadaic acid and F- ions, the Ser/Thr protein phosphatase inhibitors. Moreover, the frog enzyme does not cross-react with specific antisera directed against N-terminal fragment of human PP2A and C-terminal conserved fragment of the eukaryotic PP2A catalytic subunits. These results exclude LMW AcPase from belonging to Ser/Thr protein phosphatases: PP1c or PP2Ac. In addition to P-Tyr, this enzyme hydrolyses efficiently at acidic pH P-Tyr phosphorylated peptides (hirudin and gastrin fragments). Km value for the hirudin fragment (7.55 ± 1.59 × 10-6 M) is 2-3 orders of magnitude lower in comparison with other substrates tested. The enzyme is inhibited competitively by typical inhibitors of protein tyrosine phosphatases (PTPases): sodium orthovanadate, molybdate and tungstate. These results may suggest that the LMW AcPase of frog liver can act as PTPase in vivo. A different cellular localization and different response to inhibition by tetrahedral oxyanions (molybdate, vanadate and tungstate) provide further evidence that LMW AcPase of frog liver is distinct from the mammalian tartrate-resistant acid phosphatases.
Źródło:
Acta Biochimica Polonica; 2003, 50, 2; 555-566
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Deep molecular response (MR4.5) as a target of therapy with tyrosine kinase inhibitors. MR4.5 – goal of CML treatment
Autorzy:
Sacha, Tomasz
Powiązania:
https://bibliotekanauki.pl/articles/1065835.pdf
Data publikacji:
2014
Wydawca:
Medical Education
Tematy:
chronic myeloid leukemia
possibility cure
therapy targets
tyrosine kinase inhibitors
Opis:
Chronic myeloid leukemia (CML) accounts for 15% of diagnosed leukemias. The annual incidence in two Polish regions has been calculated for 0.7/100,000 of general population. Introduction of tyrosine kinase inhibitors (TKIs) have substantially improved not only the prognosis of CML, but also changed the treatment goals, and the expectations of patients and physicians. The goals of CML therapy include: to prevent the progression towards accelerated phase and blastic phase, to eliminate the risk of death from leukemia, to prolong the length of survival to comparable of healthy population and to attain a quality of life comparable to healthy people. Patients treated up-front with second generation TKIs (2GTKI) have a better chance to achieve faster and deeper response to therapy. Most of patients receiving 2GTKI in first line or e.g. nilotinib after initial phase of imatinib therapy can achieve very deep molecular response (MR4.5), which is a key criterion for discontinuation studies. The results of stop-trials suggest that substantial proportion of patient could achieve sustained treatment-free survival, and that the disease could be controlled despite of persistence of minimal residual disease, which does not require a clinical intervention. Patients group that could benefit most from discontinuation study include younger people, those who have achieved MR4.5 and patients reporting TKI – associated side effects. Achievement of MR4.5 could be considered as a target of CML therapy for considerable proportion of patients. The question of safe TKI dose reduction or therapy cessation should be addressed in the future planned clinical trials.
Źródło:
OncoReview; 2014, 4, 1; A27-32
2450-6125
Pojawia się w:
OncoReview
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Carbon isotope effects in the studies of the mechanism of action of tyrosine phenol-lyase
Autorzy:
Augustyniak, W.
Kański, R.
Kańska, M.
Powiązania:
https://bibliotekanauki.pl/articles/148527.pdf
Data publikacji:
2006
Wydawca:
Instytut Chemii i Techniki Jądrowej
Tematy:
12C/14C kinetic isotope effects
tyrosine phenol-lyase
Opis:
12C/14C kinetic isotope effects on the hydrolytic cleavage of tyrosine to phenol and ammonium pyruvate catalyzed by Citrobacter freundii tyrosine phenol-lyase have been determined in positions 2, 3 and ring-1' of L-tyrosine. The competitive method with dual-label approach was applied with 3',5'-ring 3H as remote label. The results revealed the change of the effect on carbon atom in position 2 during the reaction course from the high normal values to low inverse values. On the other hand, the effect values on 3 and ring-1' position remained constant during the reaction course. The discussion of these results regarding the reaction mechanism is presented.
Źródło:
Nukleonika; 2006, 51,suppl.2; 7-11
0029-5922
1508-5791
Pojawia się w:
Nukleonika
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Tyrosine kinase, Aurora kinase and leucine aminopeptidase as attractive drug targets in anticancer therapy - characterisation of their inhibitors
Autorzy:
Ziemska, J.
Solecka, J.
Powiązania:
https://bibliotekanauki.pl/articles/876592.pdf
Data publikacji:
2016
Wydawca:
Narodowy Instytut Zdrowia Publicznego. Państwowy Zakład Higieny
Tematy:
tyrosine kinase
Aurora kinase
leucine aminopeptidase
drug
anticancer therapy
enzyme inhibitor
Opis:
Cancers are the leading cause of deaths all over the world. Available anticancer agents used in clinics exhibit low therapeutic index and usually high toxicity. Wide spreading drug resistance of cancer cells induce a demanding need to search for new drug targets. Currently, many on-going studies on novel compounds with potent anticancer activity, high selectivity as well as new modes of action are conducted. In this work, we describe in details three enzyme groups, which are at present of extensive interest to medical researchers and pharmaceutical companies. These include receptor tyrosine kinases (e.g. EGFR enzymes) and non-receptor tyrosine kinases (Src enzymes), type A, B and C Aurora kinases and aminopeptidases, especially leucine aminopeptidase. We discuss classification of these enzymes, biochemistry as well as their role in the cell cycle under normal conditions and during cancerogenesis. Further on, the work describes enzyme inhibitors that are under in vitro, preclinical, clinical studies as well as drugs available on the market. Both, chemical structures of discovered inhibitors and the role of chemical moieties in novel drug design are discussed. Described enzymes play essential role in cell cycle, especially in mitosis (Aurora kinases), cell differentiation, growth and apoptosis (tyrosine kinases) as well as G1/S transition (leucine aminopeptidase). In cancer cells, they are overexpressed and only their inhibition may stop tumor progression. This review presents the clinical outcomes of selected inhibitors and argues the safety of drug usage in human volunteers. Clinical studies of EGFR and Src kinase inhibitors in different tumors clearly show the need for molecular selection of patients (to those with mutations in genes coding EGFR and Src) to achieve positive clinical response. Current data indicates the great necessity for new anticancer treatment and actions to limit off-target activity.
Nowotwory stanowią jedną z głównych przyczyn zgonów na świecie. Dostępne w lecznictwie substancje przeciwnowotworowe charakteryzują się niskim indeksem terapeutycznym jak i wysoką toksycznością. Rozwijająca się oporność komórek nowotworowych na dostępne w terapii leki przyczynia się do konieczności poszukiwania nowych punktów uchwytu/miejsc docelowych (z ang. targets) dla potencjalnych substancji przeciwnowotworowych. Obecnie prowadzonych jest również wiele prac nad nowymi związkami przeciwnowotworowymi o wysokim potencjale terapeutycznym, nowym mechanizmie działania i/bądź wyższym indeksie selektywności. W pracy, autorzy skupili uwagę na trzech grupach enzymów, będących obecnie w obszarze zainteresowań współczesnej medycyny. Omówione zostały kinazy tyrozynowe na przykładzie enzymów EGFR i Src, kinazy Aurora typu A, B i C, a także aminopeptydazy na przykładzie aminopeptydazy leucynowej. Scharakteryzowano klasyfikację enzymów, ich rolę w cyklu komórkowym w warunkach fizjologicznych i procesie nowotworowym. Opisano również inhibitory enzymów, substancje będące w trakcie badań in vitro, przedklinicznych i klinicznych jak i leki wprowadzone na rynek farmaceutyczny. Zwrócono uwagę na budowę chemiczną inhibitorów enzymów i tym samym na kierunek poszukiwań nowych leków przeciwnowotworowych. Omówione enzymy w warunkach fizjologicznych odgrywają ważną rolę w cyklu komórkowym, zwłaszcza na etapie podziału mitotycznego. Jednakże w procesie nowotworowym dochodzi do ich nadekspresji. Zjawisko to można zahamować poprzez inhibicję aktywności enzymu. Autorzy omówili wpływ inhibitorów kinaz tyrozynowych, kinaz Aurora czy aminopeptydaz leucynowych na cykl komórkowy i bezpieczeństwo stosowania tych potencjalnych leków u ludzi. Dotychczasowe badania przedkliniczne i kliniczne inhibitorów kinazy tyrozynowej typu EGFR czy Src potwierdziły konieczność selekcji pacjentów, na tych z mutacją w genie kodującym dany enzym. Badania prowadzone na wybranej grupie chorych przynosiły oczekiwany pozytywny wynik. Wiele aspektów dotyczących nowych punktów uchwytu w terapii przeciwnowotworowej wciąż wymaga dalszych prac, aczkolwiek daje również nadzieję na odkrycie skutecznych i selektywnych leków.
Źródło:
Roczniki Państwowego Zakładu Higieny; 2016, 67, 4
0035-7715
Pojawia się w:
Roczniki Państwowego Zakładu Higieny
Dostawca treści:
Biblioteka Nauki
Artykuł
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