[ 鐧诲綍] [ 鍏嶈垂娉ㄥ唽]
璇曞墏浠櫒缃? title=
浣嶇疆锛欬a href="/">棣栭〉> 浜у搧搴掽/a> > PLX51107
绔嬪嵆鍜ㄨ
鍜ㄨ绫诲瀷锛欬/div>
*濮撳悕锛欬/div>
*鐢佃瘽锛欬/div>
*鍗曚綅锛欬/div>
Email锛欬/div>
*鐣欒█鍐呭锛欬/div>
璇疯缁嗚鏄庢偍鐨勯渶姹傘€
*楠岃瘉鐮侊細
PLX51107
鏈骇鍝佷笉鍚戜釜浜洪攢鍞紝浠呯敤浣滅瀛︾爺绌讹紝涓嶇敤浜庝换浣曚汉浣撳疄楠屽強闈炵鐮旀€ц川鐨勫姩鐗╁疄楠屻€侟/div>
PLX51107鍥剧墖
CAS NO: 1627929-55-8
瑙勬牸: 鈮?8%
鍖呰涓庝环鏍硷細
鍖呰 浠锋牸(鍏?
5mg 鐢佃
10mg 鐢佃
25mg 鐢佃
50mg 鐢佃

浜у搧浠嬬粛
鐞嗗寲鎬ц川鍜屽偍瀛樻潯浠迭/div>
Molecular Weight (MW) 438.49
Formula C26H22N4O3
CAS No. 1627929-55-8
Storage -20鈩 for 3 years in powder form
-80鈩 for 2 years in solvent
Solubility(In vitro) DMSO:> 80 mM
Water: < 1mg/mL
Ethanol: < 1mg/mL
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
Synonyms PLX-51107; PLX51107; PLX 51107
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
瀹為獙鍙傝€冩柟娉旤/div>
In Vitro

In vitroactivity: PLX51107 is a novel, potent and selective BET (Bromodomain and Extra-Terminal motif) inhibitor, also called BRD4 (bromodomain and extra terminal domain) inhibitor with Kd values 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; 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. PLX51107 also interacts with the bromodomains of CBP and EP300 with Kd in the 100 nM range. PLX51107 (0.156-10 渭M) suppresses the CpG-induced proliferation of primary chronic lymphocytic leukemia (CLL) cells. PLX51107 also causes accumulation of p21 and I魏B伪, reduces c-MYC level, and modulates proapoptotic and antiapoptotic proteins. PLX51107 selectively modulates CLL driver gene.


Kinase Assay: DAVID functional annotation tool was used to identify enriched gene ontology terms in a given gene list. IPA (Qiagen Bioinformatics) software was used for functional annotation of differentially expressed genes regulated by BRD4 inhibition. Fold change information from microarray gene expression data was also provided as an input to IPA. Significantly overrepresented canonical pathways were reported. Upstream transcriptional regulators that could explain the observed changes in gene expression were identified by IPA upstream regulator analysis with a z-score cutoff of +2 for activation and 鈥? for inhibition. Overrepresented diseases and biological functions with a predicted activation state were identified by IPA diseases/biofunctions analysis with a z-score cutoff of 2 for increase and 鈥? for decrease.


Cell Assay: Primary CLL cells (1 脳 107 cells per condition) were treated with vehicle (DMSO), or 1 渭mol/L PLX51107 with or without CpG oligonucleotides (3.2 渭mol/L) for 4 hours. Cells were fixed with 1% formaldehyde for 15 minutes and quenched with 0.125 mol/L glycine. Chromatin was isolated by the addition of lysis buffer, followed by disruption with a Dounce homogenizer. Lysates were sonicated and the DNA sheared to an average length of 300 to 500 bp. See Supplementary Information for detailed cross-link procedure. Genomic DNA regions of interest were isolated using 4 渭g antibody against BRD4, H3K27ac, and RNA Pol II. Complexes were washed, eluted from the beads with SDS buffer, and subjected to RNase and proteinase K treatment. Cross-links were reversed by incubation overnight at 65掳C, and ChIP DNA was purified by phenol鈥揷hloroform extraction and ethanol precipitation.

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
Animal model Ba/F3 splenomegaly mouse model
Formulation & Dosage 20 mg/kg; qd, p.o.
References Cancer Discov. 2018 Apr;8(4):458-477.
Baidu
map