I-BET151 dihydrochloride  (Synonyms: GSK1210151A dihydrochloride)

I-BET151 dihydrochloride (GSK1210151A dihydrochloride) is a BET bromodomain inhibitor which inhibits BRD4, BRD2, and BRD3 with pIC₅₀ of 6.1, 6.3, and 6.6, respectively^[1][2].

pIC50: 6.1 (BRD4), 6.3 (BRD2), 6.6 (BRD3)^[1]

I-BET151 dihydrochloride (1 μM; 72 hours) treatment displays the majority of live cells resided in the G₀ phase and commensurate with a dose- and time-dependent decrease in cell proliferation and abrogation of bromodeoxyuridine incorporation^[2].
I-BET151 dihydrochloride (100 nM; 72 hours) causes a significant dose- and time-dependent decrease in the proportion of myeloma cells in S/G₂ phase^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

I-BET151 dihydrochloride demonstrates low blood clearance in the rat (~20% liver blood flow) and good oral systemic exposure which resulted in good oral bioavailability. High clearance is observed in the dog (~95% liver blood flow). The systemic exposure in the dog is low, resulting in a poor oral bioavailability of 16%. The high blood clearance in dog correlates well with the high intrinsic clearance observed in dog microsomes and hepatocytes, whereas the low intrinsic clearances seen in rat and mouse (mouse IVC 1.6 mL/min/g; CLb 8 mL/min/kg) correlate with lower in vivo blood clearances in these species. Due to the low systemic exposure observed in the dog, I-BET151 dihydrochloride is investigated in the mini-pig as a potential second species for toxicological evaluation where it showed low clearance (~32% liver blood flow) and good bioavailability (65%)^[1].
I-BET151 dihydrochloride (30 mg/kg; i.p.; daily for 21 days)-treats mice has four- to five fold smaller myeloma tumors and a significantly reduces rate of tumor size doubling than vehicle-treated mice^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

488.37

C₂₃H₂₃Cl₂N₅O₃

1883545-47-8

[H]Cl.[H]Cl.C[C@@H](N1C(C(C=C(OC)C(C2=C(C)ON=C2C)=C3)=C3N=C4)=C4NC1=O)C5=CC=CC=N5

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Seal J, et al. Identification of a novel series of BET family bromodomain inhibitors: Binding mode and profile of I-BET151 (GSK1210151A). Bioorg Med Chem Lett. 2012 Apr 15;22(8):2968-72.  [Content Brief]

  [2]. Chaidos A, et al. Potent antimyeloma activity of the novel bromodomain inhibitors I-BET151 and I-BET762. Blood. 2014 Jan 30;123(5):697-705.  [Content Brief]