PLX51107

SKU: orb1941073

Description

PLX51107 is a novel structurally distinct BET bromodomain inhibitor that inhibits all four BET family proteins BRD2, BRD3, BRD4, and BRDT with low nanomolar potency; exhibits modest preference for BD1 versus BD2 within each BET protein (Kd=1.6, 2.1, 1.7, and 5 nM for BD1 and 5.9, 6.2, 6.1 and 120 nM for BD2 of BRD2, BRD3, BRD4, and BRDT, respectively).potently reduces viability and proliferation of the human AML cell lines MV4-11, MOLM-13, OCI-AML3, and Kasumi-1 with IC50 of 0.17, 1.8, 0.2 and 0.2 uM, respectively; has sufficient potency and oral bioavailability to demonstrate in vivo efficacy in animal models of a variety of tumor types. Blood Cancer Phase 1 Clinical(In Vitro):PLX51107 is a potent and selective BET inhibitor, with Kds of 1.6, 2.1, 1.7, and 5 nM for BD1 and 5.9, 6.2, 6.1, and 120 nM for BD2 of BRD2, BRD3, BRD4, and BRDT, respectively. PLX51107 also interacts with the bromodomains of CBP and EP300 (Kd, in the 100 nM range). PLX51107 (0.156-10 μM) suppresses the CpG-induced proliferation of primary chronic lymphocytic leukemia (CLL) cells. PLX51107 also causes accumulation of p21 and IκBα, reduces c-MYC level, and modulates proapoptotic and antiapoptotic proteins. PLX51107 selectively modulates CLL driver genes.(In Vivo):PLX51107 (2 mg/kg, p.o.) inhibits splenomegaly by 75% in the Ba/F3 (murine IL3-dependent pro-B-cell line) splenomegaly mouse model, with the similar effect of 25 mg/kg OTX015. PLX51107 (20 mg/kg, qd, p.o.) exhibits potent antileukemic effects in disease models of aggressive chronic lymphocytic leukemia (CLL) and Richter transformation (RT) via oral administration once daily.

Key Properties

• CAS Number: 1627929-55-8
• MW: 438.487
• Purity: >98% (HPLC)
• Formula: C₂₆H₂₂N₄O₃
• SMILES: O=C(O)C1=CC=C(C2=CN([C@H](C3=NC=CC=C3)C)C4=CC(C5=C(C)ON=C5C)=CN=C42)C=C1
• Target: Bromodomain
• Solubility: DMSO : 75 mg/mL. 171.05 mM

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

PLX 51107

Quick Database Links

Gene Symbol

Bromodomain