666-15

666-15 is a potent and selective small molecule inhibitor of the cAMP response element-binding protein (CREB), a nuclear transcription factor involved in regulating gene expression in response to various extracellular signals. It inhibits CREB-mediated gene transcription with an IC50 of approximately 81 nM and demonstrates strong anticancer activity, particularly against breast cancer cell lines such as MDA-MB‑231 and MDA-MB‑468, as well as A549 (lung cancer) and MCF‑7 (breast cancer). In vivo studies show that intraperitoneal administration of 666‑15 can completely suppress tumor growth in xenograft models without significant toxicity. The compound acts by inhibiting phosphorylation and activation of CREB, thereby reducing the expression of downstream target genes like Nurr1/NR4A2. While effective via IP injection, its oral bioavailability is limited; prodrug derivatives have been developed to improve this property[1][5][6][8].

Other names

CREB inhibitorCBP-CREB Interaction Inhibitor II3-(3-Aminopropoxy)-N-(2-((3-((4-chloro-2-hydroxyphenyl)carbamoyl)naphthalen-2-yl)oxy)ethyl)-2-naphthamide, HClCREB inhibitor 666–15