WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206963
Description: PLX51107 is a potent and selective BRD4 inhibitor or BET inhibitor with novel in vitro and in vivo pharmacologic properties that emulates or exceeds the efficacy of BCR signaling agents in preclinical models of CLL. PLX51107 binds to the acetylated lysine recognition motifs in the bromodomains of the BRD4 protein, thereby preventing the binding of BRD4 to acetylated lysines on histones. This disrupts chromatin remodeling and gene expression.
MedKoo Cat#: 206963
Chemical Formula: C26H22N4O3
Exact Mass: 438.1692
Molecular Weight: 438.487
Elemental Analysis: C, 71.22; H, 5.06; N, 12.78; O, 10.95
Synonym: PLX51107; PLX-51107; PLX 51107.
IUPAC/Chemical Name: (S)-4-(6-(3,5-dimethylisoxazol-4-yl)-1-(1-(pyridin-2-yl)ethyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)benzoic acid
InChi Key: AMSUHYUVOVCWTP-INIZCTEOSA-N
InChi Code: InChI=1S/C26H22N4O3/c1-15-24(17(3)33-29-15)20-12-23-25(28-13-20)21(18-7-9-19(10-8-18)26(31)32)14-30(23)16(2)22-6-4-5-11-27-22/h4-14,16H,1-3H3,(H,31,32)/t16-/m0/s1
SMILES Code: 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
Bromodomain and extra-terminal (BET) family proteins are key regulators of gene expression in cancer. Herein, we utilize BRD4 profiling to identify critical pathways involved in pathogenesis of chronic lymphocytic leukemia (CLL). BRD4 is overexpressed in CLL and is enriched proximal to genes upregulated or de novo expressed in CLL with known functions in disease pathogenesis and progression. These genes, including key members of the B-cell receptor (BCR) signaling pathway, provide a rationale for this therapeutic approach to identify new targets in alternative types of cancer.
Prevention of the expression of certain growth-promoting genes may lead to an induction of apoptosis and an inhibition of proliferation in BRD4-overexpressing tumor cells. BRD4, a member of the human bromodomain and extra-terminal (BET) family of proteins, is a transcriptional regulator that is overexpressed in certain tumor cells and plays an important role in cellular proliferation.
1: Ozer HG, El-Gamal D, Powell B, Hing ZA, Blachly JS, Harrington B, Mitchell S,
Grieselhuber NR, Williams K, Lai TH, Alinari L, Baiocchi RA, Brinton L, Baskin E,
Cannon M, Beaver L, Goettl VM, Lucas DM, Woyach JA, Sampath D, Lehman AM, Yu L,
Zhang J, Ma Y, Zhang Y, Spevak W, Shi S, Severson P, Shellooe R, Carias H, Tsang
G, Dong K, Ewing T, Marimuthu A, Tantoy C, Walters J, Sanftner L, Rezaei H, Nespi
M, Matusow B, Habets G, Ibrahim P, Zhang C, Mathé EA, Bollag G, Byrd JC,
Lapalombella R. BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia
Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally
Distinct BET Inhibitor. Cancer Discov. 2018 Apr;8(4):458-477. doi:
10.1158/2159-8290.CD-17-0902. Epub 2018 Jan 31. PubMed PMID: 29386193; PubMed
Central PMCID: PMC5882533.