J Chem Inf Model - Polypharmacology directed compound data mining: identification of promiscuous chemotypes with different activity profiles and comparison to approved drugs.

Tópicos

{ compound(1573) activ(1297) structur(1058) }
{ structur(1116) can(940) graph(676) }
{ bind(1733) structur(1185) ligand(1036) }
{ studi(2440) review(1878) systemat(933) }
{ drug(1928) target(777) effect(648) }
{ activ(1452) weight(1219) physic(1104) }
{ data(1737) use(1416) pattern(1282) }
{ extract(1171) text(1153) clinic(932) }
{ data(3008) multipl(1320) sourc(1022) }
{ process(1125) use(805) approach(778) }
{ imag(1947) propos(1133) code(1026) }
{ sequenc(1873) structur(1644) protein(1328) }
{ assess(1506) score(1403) qualiti(1306) }
{ framework(1458) process(801) describ(734) }
{ method(984) reconstruct(947) comput(926) }
{ search(2224) databas(1162) retriev(909) }
{ howev(809) still(633) remain(590) }
{ perform(999) metric(946) measur(919) }
{ visual(1396) interact(850) tool(830) }
{ perform(1367) use(1326) method(1137) }
{ spatial(1525) area(1432) region(1030) }
{ state(1844) use(1261) util(961) }
{ model(2656) set(1616) predict(1553) }
{ data(2317) use(1299) case(1017) }
{ signal(2180) analysi(812) frequenc(800) }
{ cost(1906) reduc(1198) effect(832) }
{ group(2977) signific(1463) compar(1072) }
{ sampl(1606) size(1419) use(1276) }
{ gene(2352) biolog(1181) express(1162) }
{ time(1939) patient(1703) rate(768) }
{ model(3404) distribut(989) bayesian(671) }
{ can(774) often(719) complex(702) }
{ inform(2794) health(2639) internet(1427) }
{ system(1976) rule(880) can(841) }
{ measur(2081) correl(1212) valu(896) }
{ imag(1057) registr(996) error(939) }
{ method(1219) similar(1157) match(930) }
{ featur(3375) classif(2383) classifi(1994) }
{ imag(2830) propos(1344) filter(1198) }
{ network(2748) neural(1063) input(814) }
{ imag(2675) segment(2577) method(1081) }
{ patient(2315) diseas(1263) diabet(1191) }
{ take(945) account(800) differ(722) }
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{ treatment(1704) effect(941) patient(846) }
{ surgeri(1148) surgic(1085) robot(1054) }
{ problem(2511) optim(1539) algorithm(950) }
{ error(1145) method(1030) estim(1020) }
{ chang(1828) time(1643) increas(1301) }
{ learn(2355) train(1041) set(1003) }
{ concept(1167) ontolog(924) domain(897) }
{ clinic(1479) use(1117) guidelin(835) }
{ algorithm(1844) comput(1787) effici(935) }
{ method(1557) propos(1049) approach(1037) }
{ data(1714) softwar(1251) tool(1186) }
{ design(1359) user(1324) use(1319) }
{ control(1307) perform(991) simul(935) }
{ model(2220) cell(1177) simul(1124) }
{ care(1570) inform(1187) nurs(1089) }
{ general(901) number(790) one(736) }
{ featur(1941) imag(1645) propos(1176) }
{ case(1353) use(1143) diagnosi(1136) }
{ data(3963) clinic(1234) research(1004) }
{ studi(1410) differ(1259) use(1210) }
{ risk(3053) factor(974) diseas(938) }
{ research(1085) discuss(1038) issu(1018) }
{ system(1050) medic(1026) inform(1018) }
{ import(1318) role(1303) understand(862) }
{ model(2341) predict(2261) use(1141) }
{ studi(1119) effect(1106) posit(819) }
{ blood(1257) pressur(1144) flow(957) }
{ record(1888) medic(1808) patient(1693) }
{ health(3367) inform(1360) care(1135) }
{ model(3480) simul(1196) paramet(876) }
{ monitor(1329) mobil(1314) devic(1160) }
{ ehr(2073) health(1662) electron(1139) }
{ research(1218) medic(880) student(794) }
{ patient(2837) hospit(1953) medic(668) }
{ age(1611) year(1155) adult(843) }
{ medic(1828) order(1363) alert(1069) }
{ first(2504) two(1366) second(1323) }
{ intervent(3218) particip(2042) group(1664) }
{ activ(1138) subject(705) human(624) }
{ patient(1821) servic(1111) care(1106) }
{ use(2086) technolog(871) perceiv(783) }
{ can(981) present(881) function(850) }
{ analysi(2126) use(1163) compon(1037) }
{ health(1844) social(1437) communiti(874) }
{ high(1669) rate(1365) level(1280) }
{ 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) }
{ method(1969) cluster(1462) data(1082) }
{ method(2212) result(1239) propos(1039) }
{ detect(2391) sensit(1101) algorithm(908) }

Resumo

Increasing evidence that many pharmaceutically relevant compounds elicit their effects through binding to multiple targets, so-called polypharmacology, is beginning to change conventional drug discovery and design strategies. In light of this paradigm shift, we have mined publicly available compound and bioactivity data for promiscuous chemotypes. For this purpose, a hierarchy of active compounds, atomic property based scaffolds, and unique molecular topologies were generated, and activity annotations were analyzed using this framework. Starting from ~35000 compounds active against human targets with at least 1 ?M potency, 33 chemotypes with distinct topology were identified that represented molecules active against at least 3 different target families. Network representations were utilized to study scaffold-target family relationships and activity profiles of scaffolds corresponding to promiscuous chemotypes. A subset of promiscuous chemotypes displayed a significant enrichment in drugs over bioactive compounds. A total of 190 drugs were identified that had on average only 2 known target annotations but belonged to the 7 most promiscuous chemotypes that were active against 8-15 target families. These drugs should be attractive candidates for polypharmacological profiling.

Resumo Limpo

increas evid mani pharmaceut relev compound elicit effect bind multipl target socal polypharmacolog begin chang convent drug discoveri design strategi light paradigm shift mine public avail compound bioactiv data promiscu chemotyp purpos hierarchi activ compound atom properti base scaffold uniqu molecular topolog generat activ annot analyz use framework start compound activ human target least m potenc chemotyp distinct topolog identifi repres molecul activ least differ target famili network represent util studi scaffoldtarget famili relationship activ profil scaffold correspond promiscu chemotyp subset promiscu chemotyp display signific enrich drug bioactiv compound total drug identifi averag known target annot belong promiscu chemotyp activ target famili drug attract candid polypharmacolog profil

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