BET-IN-12

Names

[ CAS No. ]:
1800343-11-6

[ Name ]:
BET-IN-12

Biological Activity

[Description]:

BET-IN-12 is an orally avtive inhibitor of bromodomain and extra-terminal (BET) with an IC50 of 0.9 nM for BRD4[1].

[Related Catalog]:

Research Areas >> Cancer
Signaling Pathways >> Epigenetics >> Epigenetic Reader Domain

[Target]

0.9 nM (BRD4)[1]


[In Vitro]

BET-IN-12 (compound 15) (24 hours) displays BRD4 and c-Myc inhibition, MM proliferation with IC50s values of 0.9 nM, 2.0 nM, and 6.0 nM, respectively[1]. BET-IN-12 (compound 15) (24 hours) has high oxidative stability across species and low glucuronidation across species, so that translate into low orally administered minimum efficacious doses (MEDs) [1].

[In Vivo]

BET-IN-12 (compound 15) is 100% oral bioavailability in mouse[1]. BET-IN-12 (compound 15) impairs the growth of established PDX tumors (TGI = 88%) at MED = 2 mg/kg (AUC = 4800 nM•h)[1]. pharmacokinetic (PK) profile[1] dose (iv/po, mg/kg) CLp ((mL/min)/kg) Vd (L/kg) half-life (ie, h) F (%) AUC (po, nM.h) mouse 1.0/3.0 4.2 1.4 3.4 100 25000 rat 1.0/5.0 18 2.9 4.1 74 6600 dog 0.1/0.3 13 5.8 7.6 73 550 monkey 0.1/0.3 4.3 1.3 4.0 85 1900

[References]

[1]. Hill, Matthew D., et al. Development of BET Inhibitors as Potential Treatments for Cancer: Optimization of Pharmacokinetic Properties. ACS Med Chem Lett. 2022.

Chemical & Physical Properties

[ Molecular Formula ]:
C30H29D3FN5O2

[ Molecular Weight ]:
516.62

Related Compounds