U! us United States cz) Patent Application Publication — co) Pub. No.: US 2014/0234888 A1 oy oy en @ os) Obodnikoy METHOD FOR IMPROVED SELECTION OF THERAPEUTIC AGENTS, Applicant: Oleksandr Oboduikow, Kiev (UA) Inveator: Oleksande Obedaiko, Kiev (UA) Appl. No 13/771,366 Filed: Feb. 20,2013, Publication Classification Int. Cl Goin 3350 (2006.01) 1 (43) Pub, Date Aug. 21, 2014 (2) US.CL ce GOLN 335008 (201301) usp 435/29 6 ABSTRACT The current invention comprises a method of selection of therapeutic agents for relent of « particular disease ia ‘humans or other mammals in which the ratio of the eoncen: trations of thiol (SH) and disulfide (SS) groups is determined inthe blood. The therapeutic agent to be tested ‘may be used to ret a neoplasti, infectious, immunological, inflammatory, or other disorder that involves (but isnot lime ited to) the following physiological systems: respiratory. car diovascular, genitourinary, gastrointestinal (including. the liver and pancreas) neurological, musculoskeletal, immuno- Jogial, and skinUS 2014/0234888 AI METHOD FOR IMPROVED SELECTION OF ‘THERAPEUTIC AGENTS, RELATED APPLICATIONS, 10001] This application claims benefit of provisional appli «ation No. 61/633,978, FILED ON Feb. 22,2012, SUMMARY OF THE INVENTION 10002} ‘The curent invention comprises a method of selec- tion of therapeutic agents for treatment oF particular disease humans o ether mammals in which the ratio of the con ‘centrations of thiol (SH) and disulfide (—SS—) proups is, ‘determined in the blood. The therapeutic agent to be tested may be used to treat a neoplastic, infectious. immuneloical inflammatory, or other disorder that involves (but snot n= ited fo) the following physiological systems: respiratory, car diovascular, genitourinary, gasteointstinal (inching. the liver and panereas), neurological, musculoskeletal, immuno- Fogical, and skin, BACKGROUND OF THE INVENTION 10003] Ics well known that any adaptive or pathological process occurs on a background af reactive oxygen species ‘antioxidant system (AOS) and inereased fee radical Biosub- stmtes. In response, it i sotivated AOS of the cells. AOS presented low-molecular eompounds—radical traps, which Include vitamins A, C, Eand K, biolavonoids, low molecular ‘weight thiols (glutathione and ergotionein) and antiperoxide ‘enzymes (superoxide-dismutase, gluathione-peroxidase, luathione-reductase, catalase, et). The end result of such process is adaptation ofthe organism to new environmental ‘conditions or the failure of adaptive mectanisms, the devel~ ‘opment ofa pathological condition, is determined asa result, Jmerrelationship of prooxidant and antioxidant mechanisms, the ability of AOS to protet cells from excess ftee radicals ‘and peroxides, Given that almost all known diseases are jccompanied by increased free radical activity and weaken ing ofthe AOS, isa very urgent assessment ofthese systems witha view to early disgnosis and pathogenesis based treat- ‘ment of disease. ‘Thiol-Disulfde Status as an Integral Indicator of Adaptation and Nonspecific Resistance 10008} Years of research carried out under the supervision ‘of Professor Vladimir Sokolovsky (St. Petersburg, Russia) ‘suggest the leading role inthe fanetioning of the adaptive process of AOS low-molecular and macromolecular (pro- ‘eins) thiol compounds (1-4). Tio compounds hawving in its structure HS-group, its very well represented inthe cell in the form ofthe tripeptide glutathione and the many proteins ‘and enzymes. These compounds are present in the cel in t60 states the reduced (HS) and oxidized (SS) and the ‘concentration of HS-groups of 2-4 times the concentration of roups, a8 most thiol protein has a physiological activity inthe reduced state, and is the primary componeat of pl tathione redox butler system cells that support a recovery in ‘environment (Kulinsky V'N, Kolesnichenko L 8, 1990), 0005) - Thiol proteins are involved in virtually all key bio- ‘chemical processes in the body: in energy metabolism, ion ‘exchange, conducting nerve impulses to muscle contraction, secretion in, theeception, etc. The we of thiol compoundsin cell activity is extremely important and attracts the atention ‘of researchers fora long time. Even in 1936, Selye observed Aug. 21, 2014 decrease in glutathione levels in the blood of animals response tothe administration of ACTH and sugested tl ‘sco hisindex a test of sess iaflunee. Inthe 605 of ast cary wascaredoutalargeaumber ofelinical studies have Shown that variety of diseases cause the same response reducing the conecalration of HS-groups in the seria of atients, the degree of reduction of the concentration these fnvups depended on the severity of the disease: the severe Clinical eases expressed, the lower the level of 1S-aroups Jathesenim, Similar changes inthe character deni inthe study ofthe influence of various factors on the organism of ‘uals and humans (ol, emotional sues, magne ld exorvise, te) In 1976, Keak FB invited to eonsier the concentration of HS-groupss an indicatorofadepivecapac- iy ofthe erganism, but this hypothesis does not explain the ‘mechanism of quantitative changes of the thiol groups. Ia 1979, iadiirSokolosky has soggsted that, ecase thiols «ist inthe cell ino formsthe eed nd oxidized they represent single tiol-dsulide system (TDS), in nonspe- Gilie adaptive response leading importance of these forms GAiSeSs-2H1). 10006] Nomerous clinical and experimental studies ave shown that many discacs sich a coronary bear disco and ‘myocardial infreton (1, esta [2), chronic gasto and chuodnal usr Perestegina NA ta, 1993) ate toxemia oF pregnancy (2) sore throat, diphtheria, infctous mono- uclcois, typhoid fever, viral hepatitis, head ttm [1] 8 well as avers envionmental fetors (laser radiation, mage ati fc, physical activity, toxins allergens, noise) indeed Jead © a simottaneoos change in the level of reduced and conidized thiol groups. Atte sme ime reveals the ollow- ing pater: 10007] thiol—