{"id":8250,"date":"2024-02-09T08:38:25","date_gmt":"2024-02-09T07:38:25","guid":{"rendered":"https:\/\/www.iqac.csic.es\/un-farmac-anticanceros-obre-una-nova-via-de-tractament-del-parkinson\/"},"modified":"2026-06-16T10:47:20","modified_gmt":"2026-06-16T08:47:20","slug":"un-farmac-anticanceros-obre-una-nova-via-de-tractament-del-parkinson","status":"publish","type":"post","link":"https:\/\/www.iqac.csic.es\/ca\/un-farmac-anticanceros-obre-una-nova-via-de-tractament-del-parkinson\/","title":{"rendered":"Un f\u00e0rmac anticancer\u00f3s obre una nova via de tractament del Parkinson"},"content":{"rendered":"<p>Un cop entren dins de l\u2019organisme, els f\u00e0rmacs, a banda de realitzar la seva funci\u00f3 terap\u00e8utica, es transformen bioqu\u00edmicament per acci\u00f3 de la maquin\u00e0ria metab\u00f2lica, proc\u00e9s que en facilita l\u2019expulsi\u00f3. Aquesta biotransformaci\u00f3 t\u00e9 com a resultat una desaparici\u00f3 gradual del f\u00e0rmac, que es va convertint en els seus metab\u00f2lits. Aquests, al seu torn, poden assolir altes concentracions en l\u2019organisme i mostrar, tamb\u00e9, una activitat biol\u00f2gica que pot ser diferent de la del f\u00e0rmac original. \u00c9s a dir, els metab\u00f2lits i el f\u00e0rmac coexisteixen a l\u2019organisme, i poden provocar efectes diferents dels obtinguts amb les mol\u00e8cules individuals. \u00c9s el cas de Rucaparib, un medicament usat en quimioter\u00e0pia del c\u00e0ncer d\u2019ovari, de mama i, m\u00e9s recentment, del c\u00e0ncer de pr\u00f2stata, i del seu metab\u00f2lit, la mol\u00e8cula M324. Rucaparib forma part d\u2019un grup de f\u00e0rmacs dissenyats per tractar diversos tipus de c\u00e0ncers que mostren alteracions en la reparaci\u00f3 del DNA. En concret, s\u00f3n inhibidors de l\u2019enzim PARP1, implicat, precisament, en el proc\u00e9s de reparaci\u00f3 de mutacions en el material gen\u00e8tic.<\/p>\n<p>Un estudi liderat pels investigadors <strong>Albert A. Antolin<\/strong>, del programa Oncobell de l\u2019<a href=\"https:\/\/idibell.cat\/\" target=\"_blank\" rel=\"noopener\">Institut d\u2019Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL)<\/a> i ProCure de l\u2019<a href=\"https:\/\/ico.gencat.cat\/ca\/inici\" target=\"_blank\" rel=\"noopener\">Institut Catal\u00e0 d\u2019Oncologia (ICO)<\/a>, i <strong>Amadeu Llebaria<\/strong>, de l\u2019 <a href=\"https:\/\/www.iqac.csic.es\/ca\/\" target=\"_blank\" rel=\"noopener\">Institut de Qu\u00edmica Avan\u00e7ada de Catalunya (IQAC-CSIC)<\/a>, ha demostrat que Rucaparib i el seu principal metab\u00f2lit M324 exhibeixen activitats diferencials. Publicat a la revista <a href=\"https:\/\/doi.org\/10.1016\/j.chembiol.2024.01.007\" target=\"_blank\" rel=\"noopener\"><em>Cell Chemical Biology<\/em><\/a>, el treball ha analitzat Rucaparib i M324, tot fent una predicci\u00f3 computacional de l\u2019activitat del metab\u00f2lit. A l\u2019article es descriu la s\u00edntesi de M324 i el seu assaig biol\u00f2gic, i es demostra que el f\u00e0rmac i el seu metab\u00f2lit tenen activitats diferenciades i actuen de forma sin\u00e8rgica en algunes l\u00ednies cel\u00b7lulars de c\u00e0ncer de pr\u00f2stata. I que, sorprenentment, M324 redueix l\u2019acumulaci\u00f3 de la prote\u00efna \u03b1-sinucle\u00efna (un component important dels cossos de Lewy), en neurones derivades de pacients de Parkinson, una malaltia neurodegenerativa caracteritzada per un trastorn del moviment, i en la qual les neurones no produeixen les quantitats suficients del neurotransmissor dopamina.<\/p>\n<p>En concret, la sinergia demostrada entre Rucaparib i M324 en l\u00ednies cel\u00b7lulars de c\u00e0ncer de pr\u00f2stata podria tenir impacte en assajos cl\u00ednics per a estadis avan\u00e7ats d\u2019aquest tipus de c\u00e0ncer. Per altra banda, el fet que M324 sigui capa\u00e7 de reduir l\u2019acumulaci\u00f3 anormal d\u2019\u03b1-sinucle\u00efna en neurones derivades de c\u00e8l\u00b7lules mare d\u2019un pacient de Parkinson, posa en evid\u00e8ncia el potencial terap\u00e8utic d\u2019aquest metab\u00f2lit i la seva possible aplicaci\u00f3 farmacol\u00f2gica per al tractament d\u2019aquesta malaltia neurodegenerativa. Aquests resultats han estat obtinguts gr\u00e0cies a la col\u00b7laboraci\u00f3 dels grups de l\u2019IDIBELL i de l\u2019ICO liderats per <strong>Miquel \u00c0ngel Pujana<\/strong>, <strong>\u00c1lvaro Ayt\u00e9s<\/strong> i del grup d\u2019<strong>Antonella Consiglio<\/strong>, de l\u2019IDIBELL i la UB.<\/p>\n<p>\u201cGr\u00e0cies a m\u00e8todes computacionals i experimentals hem pogut caracteritzar d\u2019una manera integral, i per primera vegada, la farmacologia de la mol\u00e8cula M324\u201d afirma <strong>Antolin<\/strong>, guardonat recentment amb una beca Junior Leader de la Fundaci\u00f3 \u201cla Caixa\u201d. El primer autor del treball, <strong>Huabin Hu<\/strong>, ha fet una predicci\u00f3 exhaustiva de l\u2019activitat diferencial del f\u00e0rmac original i del seu producte, que es tradueix en espectres diferents del patr\u00f3 de fosforil\u00b7laci\u00f3 de prote\u00efnes cel\u00b7lulars. <strong>Carme Serra<\/strong>, del grup MCS del IQAC-CSIC, ha sintetitzat el metab\u00f2lit M324, la qual cosa ha perm\u00e8s verificar experimentalment, en assaigs biol\u00f2gics i cel\u00b7lulars, la predicci\u00f3 computacional. Els resultats obtinguts podrien tenir implicacions en el tractament cl\u00ednic amb Rucaparib i, alhora, obren noves oportunitats de descobriment de f\u00e0rmacs.<\/p>\n<p>En resum, l\u2019estudi apunta vers una nova perspectiva conceptual en farmacologia: la que considera el metabolisme dels f\u00e0rmacs no com un proc\u00e9s indesitjable que degrada i elimina la mol\u00e8cula terap\u00e8utica de l&#8217;organisme, sin\u00f3 que pot tenir avantatges potencials des del punt de vista terap\u00e8utic. En efecte, el treball destaca la import\u00e0ncia de caracteritzar l&#8217;activitat dels metab\u00f2lits dels f\u00e0rmacs per comprendre de manera integral la seva resposta cl\u00ednica i aplicar-la en la medicina de precisi\u00f3.<\/p>\n<p>&nbsp;<\/p>\n<p style=\"font-size: 75%;\">Huabin Hu, Carme Serra, Wenjie Zhang, Aurora Scrivo, Irene Fern\u00e1ndez-Carasa, Antonella Consiglio, Alvaro Aytes Miguel Angel Pujana, Amadeu Llebaria, Albert A. Antolin <a href=\"https:\/\/doi.org\/10.1016\/j.chembiol.2024.01.007\" target=\"_blank\" rel=\"noopener\"><strong>Identification of differential biological activity and synergy between the PARP inhibitor rucaparib and its major metabolite<\/strong><\/a>. <em>Cell Chemical Biology<\/em>. DOI: <a href=\"https:\/\/doi.org\/10.1016\/j.chembiol.2024.01.007\" target=\"_blank\" rel=\"noopener\">10.1016\/j.chembiol.2024.01.007<\/a><\/p>\n<p>&nbsp;<\/p>\n<p style=\"text-align: right;\"><strong>IDIBELL Comunicaci\u00f3 \/ IQAC-CSIC Comunicaci\u00f3<\/strong><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Un cop entren dins de l\u2019organisme, els f\u00e0rmacs, a banda de realitzar la seva funci\u00f3 terap\u00e8utica, es transformen bioqu\u00edmicament per acci\u00f3 de la maquin\u00e0ria metab\u00f2lica, proc\u00e9s que en facilita l\u2019expulsi\u00f3. Aquesta biotransformaci\u00f3 t\u00e9 com a resultat una desaparici\u00f3 gradual del f\u00e0rmac, que es va convertint en els seus metab\u00f2lits. Aquests, al seu torn, poden assolir<a class=\"more-link\" href=\"https:\/\/www.iqac.csic.es\/ca\/un-farmac-anticanceros-obre-una-nova-via-de-tractament-del-parkinson\/\">Continue reading <span class=\"screen-reader-text\">\u00abUn f\u00e0rmac anticancer\u00f3s obre una nova via de tractament del Parkinson\u00bb<\/span><\/a><\/p>\n","protected":false},"author":3,"featured_media":4438,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[73],"tags":[],"class_list":["post-8250","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","entry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.7 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Un f\u00e0rmac anticancer\u00f3s obre una nova via de tractament del Parkinson | IQAC - Institut de Qu\u00edmica Avan\u00e7ada de Catalunya - CSIC<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.iqac.csic.es\/un-farmaco-anticanceroso-abre-una-nueva-via-de-tratamiento-del-parkinson\/\" \/>\n<meta property=\"og:locale\" content=\"ca_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Un f\u00e0rmac anticancer\u00f3s obre una nova via de tractament del Parkinson | IQAC - Institut de Qu\u00edmica Avan\u00e7ada de Catalunya - CSIC\" \/>\n<meta property=\"og:description\" content=\"Un cop entren dins de l\u2019organisme, els f\u00e0rmacs, a banda de realitzar la seva funci\u00f3 terap\u00e8utica, es transformen bioqu\u00edmicament per acci\u00f3 de la maquin\u00e0ria metab\u00f2lica, proc\u00e9s que en facilita l\u2019expulsi\u00f3. Aquesta biotransformaci\u00f3 t\u00e9 com a resultat una desaparici\u00f3 gradual del f\u00e0rmac, que es va convertint en els seus metab\u00f2lits. 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