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666-15

CAS No. : 1433286-70-4

產(chǎn)品活性：666-15 is a potent and selective CREB inhibitor with an IC₅₀ of 81 nM. 666-15 suppresses tumor growth in a breast cancer xenograft model.

研究領(lǐng)域：Epigenetics

作用靶點：Epigenetic Reader Domain

In Vitro: 666-15 (73 nM; for 12 hours) significantly blocks the effects caused by MSN overexpression, including cell proliferation, invasion, soft agar colony formation ability, and the expression of CREB downstream genes. 666-15 inhibits MSN overexpression-induced CREB phosphorylation.
666-15 (1μM; pretreated 2 hour) effectively inhibits PE-induced CREB phosphorylation. 666-15 significantly decreases the protein expression of ANP and β-MHC and inhibits the activation of ER stress, including the expression of GRP78, CHOP, ATF6, and the phosphorylation of IRE1 in PE?+?siRNA?+?666-15 group and PE?+?si-CTRP3?+?666-15 group.
666-15 potently inhibits cancer cell growth. In MDA-MB-231 and MDA-MB-468 cells, the GI₅₀ for 666-15 is 73 and 46 nM, respectively. In A549 and MCF-7 cells, it exhibits robust activity as well with GI₅₀ of 0.47 and 0.31 μM. 666-15 is also found to be a rather weak inhibitor of CREB-CBP interaction with IC₅₀ of 18.27 μM. 666-15 inhibits CREB’s transcription activity in living cells independent of direct CREB or CBP binding interaction. 666-15 is very potent in inhibiting CREB’s transcription activity. 666-15 also inhibits endogenous CREB target gene expression, the transcript level of nuclear receptor related 1 protein (Nurr1/NR4A2).

In Vivo: 666-15 (10 mg/kg; IP; once a week; for 11 weeks) alone can play a good role in inhibiting the growth of breast cancer, and the combination with RP-56976 (DOC) shows a better effect.

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