BAY 299

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

BAY 299 是溴结构域和 PHD 含指 (BRPF) 家族蛋白 BRD1 和 TAF1 第二个溴结构域的有效选择性抑制剂，IC50 分别为 6 nM 和 13 nM。

BAY 299 is a potent and selective inhibitor of the bromodomain and PHD finger-containing (BRPF) family protein BRD1 and the second bromodomain of TAF1 with IC50 of 6 nM and 13 nM, respectively; dispalys >30-fold selective over BRPF1, BRPF3, BRD9, and ATAD2 and is >300-fold selective over BRD4.

BAY-299 is a dual inhibitor of the bromodomain and PHD finger (BRPF) family member BRPF2 and the TATA box binding protein-associated factors TAF1 and TAF1L. TR-FRET assays showed that BAY-299 is a potent inhibitor of BRPF2 BD with an IC50 of 67 nM, and a selectivity of 47- and 83-fold over BRPF1 and BRPF3 BDs. The profile of BAY-299 is further confirmed by AlphaScreen assay, where an IC50 of 97 nM and a selectivity of 23- and 25-fold over BRPF1 and BRPF3 BDs are measured. NanoBRET experiments show that the interaction of BRPF2 BD with histones H4 and H3.3 is blocked by BAY-299 with IC50 values of 575 and 825 nM, respectively. For TAF1 BD2, the IC50 values are 970 and 1400 nM, respectively. No inhibitory effect is observed for the interaction between BRPF1 or BRD4 and histone H4 up to 10 μM for BAY-299. BAY-299 inhibits MOLM-13, MV4-11, 769-P, Jurkat, NCI-H526, CHL-1, and 5637 cells proliferationwith GI50s of 1060, 2630, 3210, 3900, 6860, 7400, and 7980 nM, respectively.

Studies of the in vivo pharmacokinetic properties of BAY-299 in rat reveal that blood clearance is low (ca. 17% of hepatic blood flow), volume of distribution in steady-state high, terminal half-life long to very long (t1/2=10 h), and bioavailability high (F=73%). In vivo blood clearance is as anticipated based on rat liver microsome values but lower than expected based on hepatocyte data.

BAY299

Chromatin/Epigenetic

Bromodomain

Bromodomain

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2080306-23-4

429.476

C25H23N3O4

>98% (HPLC)

DMSO : 25 mg/mL 58.21 mM

O=C1N(C2=C(C)C=C(N3C)C(N(C)C3=O)=C2)C(C4=CC=C(CCCO)C5=CC=CC1=C45)=O

2-(2,3-dihydro-1,3,6-trimethyl-2-oxo-1H-benzimidazol-5-yl)-6-(3-hydroxypropyl)-1H-benz[de]isoquinoline-1,3(2H)-dione

(-20℃)

With Ice Pack

≥ 2 years