I-BET762

SKU: orb1226654

Description

I-BET762 (GSK-525762A, Molibresib) is a highly potent, selective inhibitor of BET family proteins BRD2, BRD3 and BRD4 with IC50 of 32.5-42.5 nM, does not interact with other bromodomain-containing proteins (BAZ2B, ATAD2, CREBBP and PCAF); inhibits binding of BET proteins to acetylated histones, disrupts chromatin complexes responsible for the expression of key inflammatory genes in activated macrophages, suppresses TNF-inducible key proinflammatory cytokine (il1b, il1a) and chemokine genes (ccl5, cxcl10, cxcl2/3) in BMDMs; inhibits the ability of Th1-differentiated 2D2 T cells to induce neuroinflammation in vivo in mouse model of EAE; inhibits myeloma cell proliferation both in vitro and myeloma xenograft models.Blood Cancer Phase 2 Clinical(In Vitro):Molibresib (I-BET 762) shows the highest affinity interaction with BET. Molibresib binds to the tandem bromodomains of BET with high affinity (dissociation constant Kd of 50.5-61.3 nM). Molibresib displaces, with high efficacy (half-maximum inhibitory concentration IC50 of 32.5-42.5 nM), a tetra-acetylated H4 peptide that had been pre-bound to tandem bromodomains of BET. Molibresib has high affinity for BD1/BD2 domain of BRD2/3/4 proteins. Molibresib treatment leads to a reduction in the recruitment of all three proteins to chromatin. Molibresib inhibits OPM-2 cell proliferation with IC50 of 60.15 nM.(In Vivo):The antimyeloma activity of Molibresib (I-BET 762) is tested dosed orally in an in vivo systemic xenograft model generated by injecting OPM-2 cells into NOD-SCID mice. Daily oral doses of Molibresib up to 10 mg/kg and 30 mg/kg given every other day are well tolerated with no clear impact on body weight compared with vehicle control. The plasma hLC concentration is significantly reduced in mice treated with Molibresib.

Key Properties

• CAS Number: 1260907-17-2
• MW: 423.8954
• Purity: >98% (HPLC)
• Formula: C₂₂H₂₂ClN₅O₂
• SMILES: O=C(NCC)C[C@H]1C2=NN=C(C)N2C3=CC=C(OC)C=C3C(C4=CC=C(Cl)C=C4)=N1
• Target: Bromodomain
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  The antimyeloma activity of Molibresib (I-BET 762) is tested dosed orally in an In vivo systemic xenograft model generated by injecting OPM-2 cells into NOD-SCID mice. Daily oral doses of Molibresib up to 10 mg/kg and 30 mg/kg given every other day are well tolerated with no clear impact on body weight compared with vehicle control. The plasma hLC concentration is significantly reduced in mice treated with Molibresib.
• In Vitro:
  Molibresib (I-BET 762) shows the highest affinity interaction with BET. Molibresib binds to the tandem bromodomains of BET with high affinity (dissociation constant Kd of 50.5-61.3 nM). Molibresib displaces, with high efficacy (half-maximum inhibitory concentration IC50 of 32.5-42.5 nM), a tetra-acetylated H4 peptide that had been pre-bound to tandem bromodomains of BET. Molibresib has high affinity for BD1/BD2 domain of BRD2/3/4 proteins. Molibresib treatment leads to a reduction in the recruitment of all three proteins to chromatin. Molibresib inhibits OPM-2 cell proliferation with IC50 of 60.15 nM.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

GSK525762A | GSK-525762A | I-BET-762 | Molibresib

Quick Database Links

Gene Symbol

Bromodomain