Abdel-Maksoud, Mohammed S. El-Gamal, Mohammed, I Lee, Bong S. El-Din, Mahmoud M. Gamal Jeon, Hong R. Kwon, Dow Ammar, Usama M. Mersal, Karim, I Ali, Eslam M. H. Lee, Kyung-Tae Yoo, Kyung Ho Han, Dong Keun Lee, Jae Kyun Kim, Garam Choi, Hong Seok Kwon, Young Jik Lee, Kwan Hyi Oh, Chang Hyun 2024-01-19T14:34:18Z 2024-01-19T14:34:18Z 2022-01-10 2021-05 0022-2623 https://pubs.kist.re.kr/handle/201004/117029 BRAF is an important component of MAPK cascade. Mutation of BRAF, in particular V600E, leads to hyperactivation of the MAPK pathway and uncontrolled cellular growth. Resistance to selective inhibitors of mutated BRAF is a major obstacle against treatment of many cancer types. In this work, a series of new (imidazo[2,1-b]thiazol-5-yl)pyrimidine derivatives possessing a terminal sulfonamide moiety were synthesized. Pan-RAF inhibitory effect of the new series was investigated, and structure-activity relationship is discussed. Antiproliferative activity of the target compounds was tested against the NCI-60 cell line panel. The most active compounds were further tested to obtain their IC50 values against cancer cells. Compound 27c with terminal open chain sulfonamide and 38a with a cyclic sulfamide moiety showed the highest activity in enzymatic and cellular assay, and both compounds were able to inhibit phosphorylation of MEK and ERK. Compound 38a was selected for testing its in vivo activity against melanoma. Cellular and animal activities are reported. English AMER CHEMICAL SOC Discovery of New Imidazo[2,1-b]thiazole Derivatives as Potent Pan-RAF Inhibitors with Promising In Vitro and In Vivo Anti-melanoma Activity Article 10.1021/acs.jmedchem.1c00230 1 JOURNAL OF MEDICINAL CHEMISTRY, v.64, no.10, pp.6877 - 6901 JOURNAL OF MEDICINAL CHEMISTRY 64 10 6877 6901 N scie scopus 000657351500026 2-s2.0-85107085123 Chemistry, Medicinal Pharmacology & Pharmacy Article RAF/MEK/ERK PATHWAY BIOLOGICAL-ACTIVITY ANTITUMOR-ACTIVITY BRAF MUTATIONS HUMAN HOMOLOGS LUNG-CANCER MELANOMA DABRAFENIB KINASES ACTIVATION pan-raf imidazo[2,1-b]thiazol