77173-35-4Relevant academic research and scientific papers
Structure-Guided Design of IACS-9571, a Selective High-Affinity Dual TRIM24-BRPF1 Bromodomain Inhibitor
Palmer, Wylie S.,Poncet-Montange, Guillaume,Liu, Gang,Petrocchi, Alessia,Reyna, Naphtali,Subramanian, Govindan,Theroff, Jay,Yau, Anne,Kost-Alimova, Maria,Bardenhagen, Jennifer P.,Leo, Elisabetta,Shepard, Hannah E.,Tieu, Trang N.,Shi, Xi,Zhan, Yanai,Zhao, Shuping,Barton, Michelle C.,Draetta, Giulio,Toniatti, Carlo,Jones, Philip,Geck Do, Mary,Andersen, Jannik N.
, p. 1440 - 1454 (2016)
The bromodomain containing proteins TRIM24 (tripartite motif containing protein 24) and BRPF1 (bromodomain and PHD finger containing protein 1) are involved in the epigenetic regulation of gene expression and have been implicated in human cancer. Overexpression of TRIM24 correlates with poor patient prognosis, and BRPF1 is a scaffolding protein required for the assembly of histone acetyltransferase complexes, where the gene of MOZ (monocytic leukemia zinc finger protein) was first identified as a recurrent fusion partner in leukemia patients (8p11 chromosomal rearrangements). Here, we present the structure guided development of a series of N,N-dimethylbenzimidazolone bromodomain inhibitors through the iterative use of X-ray cocrystal structures. A unique binding mode enabled the design of a potent and selective inhibitor 8i (IACS-9571) with low nanomolar affinities for TRIM24 and BRPF1 (ITC Kd = 31 nM and ITC Kd = 14 nM, respectively). With its excellent cellular potency (EC50 = 50 nM) and favorable pharmacokinetic properties (F = 29%), 8i is a high-quality chemical probe for the evaluation of TRIM24 and/or BRPF1 bromodomain function in vitro and in vivo.
BROMODOMAIN INHIBITORS FOR TREATING DISEASE
-
Paragraph 0200-0201, (2016/03/19)
Disclosed herein are compounds and compositions useful in the treatment of bromodomain-containing protein-mediated diseases, such as cancer, having the structure of Formula I: Methods of inhibiting activity of a bromodomain-containing protein in a human or animal subject are also provided.
NEW LIPOPHENOL COMPOUNDS AND USES THEREOF
-
Page/Page column 45, (2015/11/10)
The present invention relates to a compound of formula (I) wherein: - i is 0 or 1; j is 0 or 1; k is 0 or 1; - R1 and R2 are in particular H, (C1-C12)alkyl, or a group of formula C(O)R; - R is a, linear or branched, alkyl radical, comprising at least 19 carbon atoms; - R3 is H and k=0 when j=1; or, when j=0, R3 is -C(O)R or -L-C(O)R; - L, U and L" are linkers; wherein, when j=0, at least one of the groups R1; R2 and R3 comprises a radical R.
Synthesis and functionalization of inherently chiral tetraoxacalix[2] arene[2]pyridines
Pan, Shuai,Wang, De-Xian,Zhao, Liang,Wang, Mei-Xiang
supporting information, p. 6254 - 6257 (2013/02/23)
Inherently chiral tetraoxacalix[2]arene[2]pyridines containing C 2 symmetry were synthesized efficiently from a macrocyclic condensation reaction of resorcinol derivatives with 2,6-dichloro-3- nitropyridine in a one-pot reaction manner, while tetraoxacalix[2]arene[2] pyridine with an ABCD-substitution pattern was prepared in a good yield by means of a stepwise fragment coupling approach. Postmacrocyclization chemical manipulations led to functionalized tetraoxacalix[2]arene[2]pyridines. A racemic sample was resolved into enantiopure (+)- and (-)-inherently chiral compounds.
