公开(公告)号：US20210137938A1

公开(公告)日：2021-05-13

申请号：US17059297

申请日：2019-05-31

申请人： INSTITUT NATIONAL DE SANTE ET DE LA RECHERCHE MEDICALE (INSERM) ,  FUNDACION AGENCIA ARAGONESA PARA LA INVESTIGACION Y EL DESARROLLO (ARAID) ,  MIGUEL HERNANDEZ UNIVERSITY OF ELCHE ,  FUNDACION INSTITUTO DE INVESTIGACION SANITARIA ARAGON ,  CHONGQING UNIVERSITY ,  INSTITUT JEAN PAOLI & IRENE CALMETES ,  UNIVERSITÉ D'AIX-MARSEILLE ,  UNIVERSITY OF ZARAGOZA ,  INSTITUTO ARAGONES DE CIENCIAS DE LA SALUD - ARAGON INSTITUTE OF HEALTH SCIENCES ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  CONSIGLIO NAZIONALE DELLE RICERCHE- NATIONAL RESEARCH COUNCIL ITALY

发明人： Olga ABIAN FRANCO ,  Patricia SANTOFIMIA ,  Yi XIA ,  Jose Luis NEIRA ,  Bruno RIZZUTI ,  Adrian VELAZQUEZ CAMPOY ,  Ling PENG ,  Juan IOVANNA

IPC分类号： A61K31/5415 ,  A61K45/06 ,  C07D279/28 ,  C07D417/12 ,  A61P35/00

摘要： The present invention relates to the treatment of a tumor selected from the group consisting of pancreatic cancer, liver cancer, melanoma, colon cancer, glioblastoma, osteosarcoma, prostate cancer and breast cancer, more particularly pancreatic cancer. The inventors found a novel family compounds of formula (I) able to treat a variety of cancers by inhibiting NUPR1, a stress-inducible 82-amino-acid-long, intrinsically disordered member of the AT-hook family of chromatin proteins. Thus, the present invention relates to a compound of formula (I) for its use in the treatment of a tumor selected from the group consisting of pancreatic cancer, liver cancer, melanoma, colon cancer, glioblastoma, osteosarcoma, prostate cancer and breast cancer. In particular, the inventors tested compounds of formula (I) on four well characterized primary pancreatic cancer-derived cells 02.063 and LIPC (Basal subtype), Foic8b (derived from a liver metastasis) and HN14 (Classical subtype), as well as on other cellular lines derived from different tumors, i.e. U87 (glioblastoma), A375 and B16 (melanoma), U20S and SaOS (osteosarcoma), HT29, SK-CO-1 and LS174T (colon cancer), HepG2 (hepatocarcinoma), PC3 (prostate) and MDA-MB-231 (breast cancer). The compounds per se are also claimed.