J Chem Inf Model - Probing the bioactivity-relevant chemical space of robust reactions and common molecular building blocks.

Tópicos

{ compound(1573) activ(1297) structur(1058) }
{ drug(1928) target(777) effect(648) }
{ general(901) number(790) one(736) }
{ structur(1116) can(940) graph(676) }
{ bind(1733) structur(1185) ligand(1036) }
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{ studi(1410) differ(1259) use(1210) }
{ sampl(1606) size(1419) use(1276) }
{ process(1125) use(805) approach(778) }
{ motion(1329) object(1292) video(1091) }
{ visual(1396) interact(850) tool(830) }
{ health(3367) inform(1360) care(1135) }
{ research(1218) medic(880) student(794) }
{ data(3008) multipl(1320) sourc(1022) }
{ inform(2794) health(2639) internet(1427) }
{ imag(1057) registr(996) error(939) }
{ sequenc(1873) structur(1644) protein(1328) }
{ imag(2830) propos(1344) filter(1198) }
{ framework(1458) process(801) describ(734) }
{ chang(1828) time(1643) increas(1301) }
{ featur(1941) imag(1645) propos(1176) }
{ perform(999) metric(946) measur(919) }
{ research(1085) discuss(1038) issu(1018) }
{ spatial(1525) area(1432) region(1030) }
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{ ehr(2073) health(1662) electron(1139) }
{ state(1844) use(1261) util(961) }
{ patient(2837) hospit(1953) medic(668) }
{ model(2656) set(1616) predict(1553) }
{ age(1611) year(1155) adult(843) }
{ medic(1828) order(1363) alert(1069) }
{ signal(2180) analysi(812) frequenc(800) }
{ group(2977) signific(1463) compar(1072) }
{ first(2504) two(1366) second(1323) }
{ intervent(3218) particip(2042) group(1664) }
{ activ(1138) subject(705) human(624) }
{ time(1939) patient(1703) rate(768) }
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{ use(2086) technolog(871) perceiv(783) }
{ analysi(2126) use(1163) compon(1037) }
{ health(1844) social(1437) communiti(874) }
{ cancer(2502) breast(956) screen(824) }
{ use(976) code(926) identifi(902) }
{ use(1733) differ(960) four(931) }
{ result(1111) use(1088) new(759) }
{ implement(1333) system(1263) develop(1122) }
{ survey(1388) particip(1329) question(1065) }
{ estim(2440) model(1874) function(577) }
{ decis(3086) make(1611) patient(1517) }
{ activ(1452) weight(1219) physic(1104) }
{ method(1969) cluster(1462) data(1082) }
{ method(2212) result(1239) propos(1039) }
{ detect(2391) sensit(1101) algorithm(908) }

Resumo

In the search for new bioactive compounds, there is a trend toward increasingly complex compound libraries aiming to target the demanding targets of the future. In contrast, medicinal chemistry and traditional library design rely mainly on a small set of highly established and robust reactions. Here, we probe a set of 58 such reactions for their ability to sample the chemical space of known bioactive molecules, and the potential to create new scaffolds. Combined with ~26,000 common available building blocks, the reactions retrieve around 9% of a scaffold-diverse set of compounds active on human target proteins covering all major pharmaceutical target classes. Almost 80% of generated scaffolds from virtual one-step synthesis products are not present in a large set of known bioactive molecules for human targets, indicating potential for new discoveries. The results suggest that established synthesis resources are well suited to cover the known bioactivity-relevant chemical space and that there are plenty of unexplored regions accessible by these reactions, possibly providing valuable "low-hanging fruit" for hit discovery.

Resumo Limpo

search new bioactiv compound trend toward increas complex compound librari aim target demand target futur contrast medicin chemistri tradit librari design reli main small set high establish robust reaction probe set reaction abil sampl chemic space known bioactiv molecul potenti creat new scaffold combin common avail build block reaction retriev around scaffolddivers set compound activ human target protein cover major pharmaceut target class almost generat scaffold virtual onestep synthesi product present larg set known bioactiv molecul human target indic potenti new discoveri result suggest establish synthesi resourc well suit cover known bioactivityrelev chemic space plenti unexplor region access reaction possibl provid valuabl lowhang fruit hit discoveri

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