GSK1210151A

Biological Activity

GSK1210151A (I-BET151) is a novel BET bromodomain inhibitor which blocks recruitment of BET to chromatin. GSK1210151A exhibits potent selectivity over an extensive range of diverse protein types such as COX-2, P450, Aurora B, GSK3β, PI3K-γ, GPCR, ion channels and transporters. GSK1210151A displaces BRD3 and BRD4, PAFc and SEC components from chromatin resulting in inhibition of transcription at key genes (BCL2, C-MYC and CDK6) involved in the initiation of mixed lineage leukemia (MLL). GSK1210151A (I-BET151) induces apoptosis and G0/G1 cell cycle arrest in MLL-fusion leukemic cell lines in vitro with IC50 values of 15, 26, 120 and 192 nM for NOMO1, MV4;11, MOLM13 and RS4;11 cell lines respectively. GSK1210151A reduces BCL2 expression in NOMO1 cells. In vivo, GSK1210151A (I-BET151) improves survival and shows good oral bioavailability in both the rat and minipig as well as demonstrating efficient suppression of bacterial induced inflammation and sepsis in a murine.

Product Citations

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  BMC Biol. 2021 May 20;19(1):108.

  Very long intergenic non-coding (vlinc) RNAs directly regulate multiple genes in cis and trans
  GSK1210151A purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Cell Stem Cell (2015). Figure 2. GSK1210151A
	Method	Efficiently Generating CiNs
	Cell Lines	TUJ1-stained cells
	Concentrations	100 μm
	Incubation Time	14 days
	Results	We found that an additional small molecule, I-BET151, dramatically enhanced the reprogramming rate (with a 90% TUJ1-positive cell yield) and neurite outgrowth of the iNs

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information

References

[1] Seal J, et al. Bioorg Med Chem Lett. Identification of a novel series of BET family bromodomain inhibitors: binding mode and profile of I-BET151 (GSK1210151A).

[2] Dawson MA, et al. Nature. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia.