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.
IC50&Target
IC50: 81 nM (CREB)
体外研究
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).
Cell Proliferation Assay
Cell Line:
CTRL or MSN-overexpressing MDA-MB-231 cells
Concentration:
73 nM
Incubation Time:
For 12hours
Result:
Significantly blocked the cell proliferation caused by MSN overexpression.
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.
Animal Model:
1-month-old female nude mice with MDA-MB-231 or T47D cells
Dosage:
10 mg/kg
Administration:
IP; once a week; for 11 weeks
Result:
Played a good role in inhibiting the growth of breast cancer.
分子式
C33H31Cl2N3O5
分子量
620.52
CAS号
1433286-70-4
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : 125 mg/mL (201.44 mM; ultrasonic and warming and heat to 60°C)