TY - JOUR
T1 - State of the art of Smo antagonists for cancer therapy
T2 - Advances in the target receptor and new ligand structures
AU - Espinosa-Bustos, Christian
AU - Mella, Jaime
AU - Soto-Delgado, Jorge
AU - Salas, Cristian O.
N1 - Funding Information:
This review was supported by grant (no. 1161816) from the Fondo Nacional de Desarrollo Científico y Tecnologico (FONDECYT), Santiago, Chile. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Since the Hedgehog signaling pathway has been associated with cancer, it has emerged as a therapeutic target for cancer therapy. The main target among the key Hedgehog proteins is the GPCR-like Smo receptor. Therefore, some Smo antagonists that have entered clinical trials, including the US FDA-approved drugs vismodegib and sonidegib, to treat basal cell carcinoma and medulloblastoma. However, early resistance of these drugs has spawned the need to understand the molecular bases of this phenomena. We therefore reviewed details about Smo receptor structures and the best Smo antagonist chemical structures. In addition, we discussed strategies that should be considered to develop new, safer generations of Smo antagonists that avoid current clinical limitations.
AB - Since the Hedgehog signaling pathway has been associated with cancer, it has emerged as a therapeutic target for cancer therapy. The main target among the key Hedgehog proteins is the GPCR-like Smo receptor. Therefore, some Smo antagonists that have entered clinical trials, including the US FDA-approved drugs vismodegib and sonidegib, to treat basal cell carcinoma and medulloblastoma. However, early resistance of these drugs has spawned the need to understand the molecular bases of this phenomena. We therefore reviewed details about Smo receptor structures and the best Smo antagonist chemical structures. In addition, we discussed strategies that should be considered to develop new, safer generations of Smo antagonists that avoid current clinical limitations.
KW - anticancer compounds
KW - cancer therapy
KW - Hedgehog signaling pathway
KW - Smo antagonists
KW - Smoothened receptor
UR - http://www.scopus.com/inward/record.url?scp=85064121690&partnerID=8YFLogxK
U2 - 10.4155/fmc-2018-0497
DO - 10.4155/fmc-2018-0497
M3 - Review article
C2 - 30912670
AN - SCOPUS:85064121690
SN - 1756-8919
VL - 11
SP - 617
EP - 638
JO - Future Medicinal Chemistry
JF - Future Medicinal Chemistry
IS - 6
ER -
