Author/Editor		Vidic, Iztok; Šuput, Dušan; Milisav, Irina
Title		Modulatorji apoptoze kot nova zdravila
Translated title		Modulators of apoptosis in drug development
Type		članek
Source		Farm Vestn
Vol. and No.		Letnik 57
Publication year		2006
Volume		str. 150-4
Language		slo
Abstract		Abstract: Defects in regulation of apoptosis result in a number of human diseases for which there are no adequate medical or pharmacological treatments. Many drug discovery studies have focused on small molecular modulators of apoptosis-relevant proteins, like caspases, protein kinases, inhibitors of apoptotic proteins (IAP), Bcl-2 family proteins and others. For example, preclinical studies of reversible caspase-3 inhibitor have shown its potential neuroprotective role in animal models of Huntington disease. An irreversible broad spectrum caspase inhibitor for chronic hepatitis C virus infection is in the phase II clinical trials. An inhibitor of tyrosine kinase involved in the regulation of cell proliferation is being used for the treatment of chronic myeloid leukaemia and some gastrointestinal tumours since 2001. Modern drug development strategies involve also the use of antisense mRNA in cancer treatment. Among the most successful is the antisense targeting of BCL-2, which is currently being reviewed for the approval by the European Medicines Agency. The knowledge about the functions of proteins involved in apoptosis and of their modulators is therefore crucial for designing new drugs, which promote or suppress apoptosis according to the aetiology of disease.
Summary		Povzetek: Vzrok mnogih bolezni, za katere še ne obstajajo učinkoviti načini zdravljenja, so napake v regulaciji programirane celične smrti (apoptoze). Mnoge raziskave razvoja zdravil za to bolezni so zato osredotočene na možnosti uravnavanja aktivnosti beljakovin, ki so udeležene v apoptozi, npr. kaspaz, proteinskih kinaz, inhibitorjev apoptotskih beljakovin IAP, beljakovin družine Bcl-2 in drugih. Spodaj so navedeni nekateri primeri uporabe modulatorjev apoptotskih beljakovin kot zdravila. V 2. fazi kliničnih preizkusov je uporaba široko spektralnega inhibitorja kaspaz za zdravljenje kroničnega hepatitisa C. V fazi predkliničnih raziskav je inhibitor kaspaze-3, ki je potencialno uporaben za zdravljenje Huntingtonove bolezni. Od leta 2001 je v uporabi inhibitor tirozinske kinaze, ki ga uporabljajo za zdravljenje levkemije in nekaterih gastrointestinalnih tumorjev. Vse pomembnejša v sodobnem pristopu k razvoju zdravil postaja tudi tehnika uporabe nasprotnosmiselnih oligonukleotidov (ang. antisense). Med najuspešnejšimi pristopi je utišanje gena za protein BCL-2, ki je v zaključnih fazah kliničnih preizkusov in ga že vrednotijo na Evropski agenciji za zdravila. Poznavanje funkcij beljakovin v apoptozi in njihovih modulatorjev je klučno za razvoj novih zdravil s katerimi lahko prožimo ali zavremo potek apoptoze v skladu z etiologijo bolezni.
Descriptors		APOPTOSIS HEPATITIS C HUNTINGTON'S DISEASE LEUKEMIA OLIGONUCLEOTIDES, ANTISENSE PROTEIN KINASES