Alobresib (C09-0735-685)

InformationAlobresib (GS-5829) Alobresib (GS-5829) is a novel BET inhibitor that represents a highly effective therapeutics agent against recurrent/chemotherapy-resistant USC-overexpressing c-Myc. Alobresib (GS-5829) inhibits CLL cell proliferation and induces leukemia cell apoptosis through deregulation of key signaling pathways, such as BLK , AKT , ERK1/2 , and MYC . Alobresib (GS-5829) also inhibits NF-κB signaling.TargetsBET ; BLK ; Akt ; ERK1/2 ; MYC 33297,In vitroIn-vitro experiments demonstrates high sensitivity of USC cell-lines to the exposure to GS-5829 causing a dose-dependent decrease in the phosphorylated levels of c-Myc and a dose-dependent increase in caspase activation (apoptosis). GS-5829 inhibits CLL cell proliferation and induces leukemia cell apoptosis through deregulation of key signaling pathways, such as BLK, AKT, ERK1/2, and MYC. IκBα modulation indicates that GS-5829 also inhibits NF-κB signaling. GS-5829-induced apoptosis results from an imbalance between positive (BIM) and negative regulators (BCL-XL) of the intrinsic apoptosis pathway.In vivoGS-5829 has impressive activity against USC primary tumors as well as USC xenografts. Assessment of c-Myc expression in tumors exposed to the GS-5829 demonstrates down-regulation of both total and phospho c-Myc proteins. GS-5829 demonstrates excellent bioavailability after oral administration and is significantly more effective than JQ1 at the doses used in comparative experiments in vivo against USC xenografts. Clinical studies with GS-5829 in USC patients harboring disease resistant to standard salvage chemotherapy are warranted.Cell Research(from reference)Cell lines：PBMC, MEC-1 Concentrations：100 nM, 200 nM, 400 nM, 800 nM Incubation Time：72 h, 24 h. Specifications and Purity: 98%. Molecular Formula: C26H23N5O2. Molecular Weight: 437.49. PubChem CID: 86281210. Isomeric SMILES: CC1=C(C(=NO1)C)C2=CC(=C3C(=C2)NC(=N3)C4CC4)C(C5=CC=CC=N5)(C6=CC=CC=N6)O. Related Document: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/A414297-SCI_a01085b2d336db5af54eb0d21c830722.pdf