1883429-21-7 Usage
Description
BI-7273 is a potent BRD9 bromodomain inhibitor (Kd = 15.4 nM; IC50 = 19 nM) that less effectively inhibits the functionally and structurally related BRD7 bromodomain (IC50 = 117 nM). It is without effect against the bromodomains of BRD2 and BRD4, as well as a panel of kinases. BI-7273 inhibits the growth of EOL-1 acute myeloid leukemia cells in vitro (EC50 = 1.4 μM).
in vitro
bi-7273 was previously demonstrated to mimic genetic perturbation of brd9. bi-7273 could also target brd7 bd, a bd protein that was found in a subclass of swi/snf remodelling complexes sharing high sequence homology with brd9. in addition, bi-7273 was able to form an additional positive interaction with the carbonyl of asn100 in brd9. furthermore, bi-7273 showed no measurable activity against bet family bds even up to a concentration of 100 μm in the biochemical alpha assay [1].
in vivo
in order to explore the potential of bi-7273 as in-vivo chemical probe, female bomtac:nmrifoxn1nu mice was orally administered two doses at 20 and 180 mg/ kg and the concentration of bi-7273 in plasma over time was measured. results showed that dose-dependent but nonlinear auc was observed for bi-7273, achieving exposure that was higher compared to the ec50 level determined for bi-7273 in proliferation assays with eol-1 cells [1].
IC 50
19 and 117 nm for brd9 and brd7, respectively.
references
[1] martin lj et al. structure-based design of an in vivo active selective brd9 inhibitor. j med chem.2016 may 26;59(10):4462-75.
Check Digit Verification of cas no
The CAS Registry Mumber 1883429-21-7 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,8,8,3,4,2 and 9 respectively; the second part has 2 digits, 2 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 1883429-21:
(9*1)+(8*8)+(7*8)+(6*3)+(5*4)+(4*2)+(3*9)+(2*2)+(1*1)=207
207 % 10 = 7
So 1883429-21-7 is a valid CAS Registry Number.
1883429-21-7Relevant articles and documents
COMPOUNDS AND USES THEREOF
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Page/Page column 273; 274, (2020/08/22)
The present invention relates to compositions and methods for the treatment of BAF-related disorders, such as cancers and viral infections.
Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor
Martin, Laetitia J.,Koegl, Manfred,Bader, Gerd,Cockcroft, Xiao-Ling,Fedorov, Oleg,Fiegen, Dennis,Gerstberger, Thomas,Hofmann, Marco H.,Hohmann, Anja F.,Kessler, Dirk,Knapp, Stefan,Knesl, Petr,Kornigg, Stefan,Müller, Susanne,Nar, Herbert,Rogers, Catherine,Rumpel, Klaus,Schaaf, Otmar,Steurer, Steffen,Tallant, Cynthia,Vakoc, Christopher R.,Zeeb, Markus,Zoephel, Andreas,Pearson, Mark,Boehmelt, Guido,McConnell, Darryl
, p. 4462 - 4475 (2016/06/13)
Components of the chromatin remodelling switch/sucrose nonfermentable (SWI/SNF) complex are recurrently mutated in tumors, suggesting that altering the activity of the complex plays a role in oncogenesis. However, the role that the individual subunits play in this process is not clear. We set out to develop an inhibitor compound targeting the bromodomain of BRD9 in order to evaluate its function within the SWI/SNF complex. Here, we present the discovery and development of a potent and selective BRD9 bromodomain inhibitor series based on a new pyridinone-like scaffold. Crystallographic information on the inhibitors bound to BRD9 guided their development with respect to potency for BRD9 and selectivity against BRD4. These compounds modulate BRD9 bromodomain cellular function and display antitumor activity in an AML xenograft model. Two chemical probes, BI-7273 (1) and BI-9564 (2), were identified that should prove to be useful in further exploring BRD9 bromodomain biology in both in vitro and in vivo settings.
