Wyniki wyszukiwania

1

Nowe leki otrzymane przy udziale technologii rekombinowanego DNA

100%

Kiec-Kononowicz K.

Biotechnologia

|

2004

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nr 3

87-100

2

Wykorzystanie cytochromow w biotechnologii farmaceutycznej

63%

Godawska A., Kiec-Kononowicz K.

Biotechnologia

|

2004

|

nr 3

166-183

3

Development of novel cellular model for affinity studies of histamine H4 receptor ligands

63%

Karcz T., Kiec-Kononowicz K.

Acta Biochimica Polonica

|

2013

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tom 60

|

nr 4

The G protein-coupled histamine H4 receptor (H4R) is the last member of histamine receptors family discovered so far. Its expression pattern, together with postulated involvement in a wide variety of immunological and inflammatory processes make histamine H4 receptor an interesting target for drug development. Potential H4R ligands may provide an innovative therapies for different immuno-based diseases, including allergy, asthma, pruritus associated with allergy or autoimmune skin conditions, rheumatoid arthritis and pain. However, none of successfully developed selective and potent histamine H4 receptor ligands have been introduced to the market up to date. For that reason there is still a strong demand for pharmacological models to be used in studies on potent H4R ligands. In current work we present the development of novel mammalian cell line, stably expressing human histamine H4 receptor, with use of retroviral transduction approach. Obtained cell line was pharmacologically characterized in radioligand binding studies and its utility for affinity testing of potent receptor ligands was confirmed in comparative studies with the use of relevant insect cells expression model. Obtained results allow for statement that developed cellular model may be successfully employed in search for new compounds active at histamine H4 receptor.

4

Porownanie metabolizmu prazikwantelu in silico i in vitro

51%

Godawska A., Pekala E., Kiec-Kononowicz K.

Biotechnologia

|

2005

|

nr 1

215-222

5

Hydantoinazy, ich znaczenie, podzial i zastosowanie w biotechnologii

51%

Latacz G., Pekala E., Kiec-Kononowicz K.

Biotechnologia

|

2006

|

nr 2

189-205

6

The study of cellular cytotoxicity of argireline - an anti - aging peptide

45%

Grosicki M., Latacz G., Szopa A., Cukier A., Kiec-Kononowicz K.

Acta Biochimica Polonica

|

2014

|

tom 61

|

nr 1

Argireline® is well know, innovative anti-aging product used in the cosmetic market. This short chain peptide is used as active ingredient in dermal ointment and creams. Argireline® prevents formation of skin lines and wrinkles in a very similar way to the botulinum toxin (Botox), inhibiting neurotransmitter release at the neuromuscular junction. Argireline® does not require under skin muscle injections and it is believed to be relatively safe. However, despite the fact that some toxicity data has been provided by the product manufacturer, there is an evident lack of reliable information about cytotoxicity of argireline® in the literature. The aim of the presented study was to estimate the antiproliferation effect of argireline® solution in several concentrations. The influence of argireline® on cellular proliferation was examined against: human embryonic kidney HEK-293 cell line, human neuroblastoma IMR-32 cell line, and human primary skin fibroblasts. Tests were performed using formazan-based cell proliferation assay: EZ4U, which allows to measure the efficiency of mitochondrial oxidative activity in living cells. The argireline® inhibitory concentration, IC50 values were calculated and the results were compared to the IC50 value of the reference compound: doxorubicin. In conclusion, the considered method resulted in dose-dependent argireline® anti-proliferation effects. However, the significant cytotoxicity of argireline® solution was observed under 18 to 10 000 fold higher concentrations (depending on cells that were examined) in comparison to doxorubicin.

7

Metabolic stability as a challenge in the early stage of drug discovery process - in vitro determination of metabolic pathways for new promising 5-HT7R ligands

45%

Lubelska A., Latacz G., Kucwaj-Brysz K., Kiec-Kononowicz K., Handzlik J.

Acta Biochimica Polonica

|

2018

|

tom 65

|

nr S2

8

The central histamine level in rat model of vascular dementia

39%

Stasiak A., Mussur M., Unzeta M., Lazewska D., Kiec-Kononowicz K., Fogel W. A.

Journal of Physiology and Pharmacology

|

2011

|

tom 62

|

nr 5

9

Four close bupranolol analogues are antagonists at the low-affinity state of beta1-adrenoceptors

33%

Zelaszczyk D., Kozlowska H., Baranowska U., Baranowska M., Reutelsterz A., Kiec-Kononowicz K., Malinowska B., Schlicker E.

Journal of Physiology and Pharmacology

|

2009

|

tom 60

|

nr 1

51-60

Bupranolol is an antagonist at the cardiostimulatory low-affinity state of ß1-adrenoceptors and we were interested whether this effect is shared by its fluorine (GD-6), methyl (DZ-51) and isopropyl analogue (DZ-13) and by the analogue hydroxylated at the tertiary butyl moiety (DZ-52). (-)-Bupranolol and compounds (-)-GD-6, (+)-GD-6, (-)-DZ-13, (+)-DZ-13, DZ-51 and DZ-52 antagonized the CGP 12177-induced tachycardia in pithed rats with “apparent pA2 values” of 6.1, 6.1, 4.6, 5.5, 4.6, 5.1 and 5.3, respectively. For comparison, their potencies and affinities at the high-affinity state of ß1-adrenoceptors were determined, using the xamoterol-induced tachycardia in pithed rats and [3H]CGP 12177 binding to rat cerebrocortical membranes. The respective “apparent pA2 values” in the functional experiments were 7.9, 8.1, 5.4, 8.4, 5.7, 7.3 and 6.8 and the pKi values in the binding experiments were 8.8, 8.4, 6.9, 8.5, 6.7, 8.4 and 8.2. In conclusion, (-)-bupranolol and its fluorine analogue (-)-GD-6 are equipotent at the low-affinity state of ß1-adrenoceptors. The stereoselectivity of GD-6 and DZ-13 suggests that the low-affinity state is indeed a receptor.

10

Low-basicity agonists of serotonin 5-HT7 receptors

27%

Hogendorf A. S., Hogendorf A., Kurczab R., Satala G., Lenda T., Walczak M., Latacz G., Handzlik J., Kiec-Kononowicz K., Wieronska J., Wozniak M., Cieslik P., Bugno R., Staron J., Bojarski A. J.

Acta Neurobiologiae Experimentalis

|

2017

|

tom 77

|

nr Suppl.1

The 5-HT7R is involved in many physiological processes, i.e. the regulation of body temperature, circadian rhythm, learning and memory, as well as pathophysiological processes such as mood disorders, anxiety, schizophrenia and pain. None of the known 5-HT7R agonists qualify as perfect radioligand candidates, mainly due to their poor selectivity, metabolic stability or non-optimal ADME properties. Development of new ligands of 5-HT7R of the unique structure and properties. The compounds were concisely synthesized using van Leusen multi-component protocol and receptor affinity (5‑HT7, 1A, 2A, 6, and D2) was tested in radioligand binding assays. The intrinsic clearance was determined using human liver microsomes, whereas cytotoxicity was measured on HEK-293 and HepG2 cells. The pharmacokinetics of a lead compound was tested on CD-1 mice at 5 mg/kg dose (i.p.). The compound ability to reverse MK-801 induced impairment in novel object recognition test was conducted on Albino Swiss mice. Results: We have developed a series of 5-HT7R ligands, which are one of the very few examples of low-basicity aminergic receptor agonists. Lead compounds exhibited high affinity for the 5‑HT7R as well as high efficacy as agonists, excellent selectivity over related CNS targets, high metabolic stability and low toxicity. Docking to 5-HT7R homology models indicated a plausible binding mode which explain the unusually high selectivity. A rapid absorption to the blood, high blood-brain barrier permeation and a very high peak concentration in the brain were found for the lead compound. It was also found active in the NOR test. Because the compounds fulfill all the requirements needed for a PET radioligand a synthetic method which enables the incorporation of 11C isotope was developed. The obtained group of selective, low-basicity 5-HT7R receptor agonists has a great potential to be developed as pharmacological tools, radioligands or drug candidates. FINANCIAL SUPPORT: The study was partially supported by the Polish-Norwegian Research Programme operated by the National Centre for Research and Development under the Norwegian Financial Mechanism 2009–2014 in the frame of the Project PLATFORMex (Pol-Nor/198887/73/2013), www.platformex.eu.

Ograniczanie wyników

Nowe leki otrzymane przy udziale technologii rekombinowanego DNA

Wykorzystanie cytochromow w biotechnologii farmaceutycznej

Development of novel cellular model for affinity studies of histamine H4 receptor ligands

Porownanie metabolizmu prazikwantelu in silico i in vitro

Hydantoinazy, ich znaczenie, podzial i zastosowanie w biotechnologii

The study of cellular cytotoxicity of argireline - an anti - aging peptide

Metabolic stability as a challenge in the early stage of drug discovery process - in vitro determination of metabolic pathways for new promising 5-HT7R ligands

The central histamine level in rat model of vascular dementia

Four close bupranolol analogues are antagonists at the low-affinity state of beta1-adrenoceptors

Low-basicity agonists of serotonin 5-HT7 receptors