WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7150
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Conference Object A Novel Inhibitor for Krasg12c Mutant Lung Carcinoma(International Association for the Study of Lung Cancer, 2020) Khan, H. Y.; Li, Y.; Aboukameel, A.; Mpilla, G.; Sexton, R.; Kanbur, Tuğçe; Nagasaka, M.; Çetinkaya, Hakkı; Çağır, AliMutations in KRAS are among the most common aberrations in cancer. However, despite considerable research efforts, KRAS remains a challenging therapeutic target. In recent years, there has been a drive to develop KRAS mutant specific drugs. Among the different known mutations, the KRASG12C (glycine 12 to cysteine) has been considered druggable. Studies have shown that due in part to the close proximity of Cysteine 12 to both the nucleotide pocket and the switch regions, thiol-reactive compounds can bind to the active site covalently and inhibit KRASG12C mutation-driven signaling. The absence of this particular cysteine residue in wild-type KRAS makes such an approach very selective towards cancer cells.Article Citation - WoS: 8Citation - Scopus: 9Crm1 Inhibitory and Antiproliferative Activities of Novel 4'-alkyl Substituted Klavuzon Derivatives(Elsevier Ltd., 2017) Kanbur, Tuğçe; Kara, Murat; Kutluer, Meltem; Şen, Ayhan; Delman, Murat; Alkan, Aylin; Otaş, Hasan Ozan; Akçok, İsmail; Çağır, AliKlavuzons are 6-(naphthalen-1-yl) substituted 5,6-dihydro-2H-pyran-2-one derivatives showing promising antiproliferative activities in variety of cancer cell lines. In this work, racemic syntheses of nine novel 4′-alkyl substituted klavuzon derivatives were completed in eight steps and anticancer properties of these compounds were evaluated. It is found that size of the substituent has dramatic effect over the potency and selectivity of the cytotoxic activity in cancerous and healthy pancreatic cell lines. The size of the substituent can also effect the CRM1 inhibitory properties of klavuzon derivatives. Strong cytotoxic activity and CRM1 inhibition can be observed only when a small substituent present at 4′-position of naphthalen-1-yl group. However, these substituents makes the molecule more cytotoxic in healthy pancreatic cells rather than cancerous pancreatic cells. Among the tested compounds 1,2,3,4-tetrahydrophenanthren-9-yl substituted lactone was the most cytotoxic compound and its antiproliferative activity was also tested in 3D spheroids generated from HuH-7 cell lines.