![]() XP-524 structure
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Common Name | XP-524 | ||
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CAS Number | 2344825-52-9 | Molecular Weight | 552.653 | |
Density | N/A | Boiling Point | N/A | |
Molecular Formula | C30H28N6O3S | Melting Point | N/A | |
MSDS | N/A | Flash Point | N/A |
Use of XP-524XP-524 (XL-223, XP524) is a potent, dual-BET/EP300 inhibitor, inhibits BRD4-BD (IC50=5.8 nM) and BRD4-BD2 (IC50=1.5 nM).XP-524 binds strongly to and inhibits EP300 and CBP proteins with IC50 of 28 and 116 nM, respectively.XP-524 (XL-223) showed high potency and selectivity (Kd < 1 nM) across BET family proteins. Selectivity for BRD proteins over all other bromodomain proteins was >400-fold.XP-524 significantly decreased expression of Myc pathway oncogenes such as c-MYC and n-MYC, increased expression of CDKN1B, a tumor suppressor that prevents the activation of the cyclin-D/CDK4 complex, and also reduced expression of cyclin-D (CCND1) itself.XP-524 showed increased potency and superior tumoricidal activity than the benchmark BET inhibitor JQ-1 in vitro, with comparable efficacy to higher-dose JQ-1 combined with the EP300/CBP inhibitor SGC-CBP30.XP-524 prevented KRAS-induced, neoplastic transformation in vivo and extended survival in two transgenic mouse models of aggressive PDAC. |
Name | XP-524 |
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Description | XP-524 (XL-223, XP524) is a potent, dual-BET/EP300 inhibitor, inhibits BRD4-BD (IC50=5.8 nM) and BRD4-BD2 (IC50=1.5 nM).XP-524 binds strongly to and inhibits EP300 and CBP proteins with IC50 of 28 and 116 nM, respectively.XP-524 (XL-223) showed high potency and selectivity (Kd < 1 nM) across BET family proteins. Selectivity for BRD proteins over all other bromodomain proteins was >400-fold.XP-524 significantly decreased expression of Myc pathway oncogenes such as c-MYC and n-MYC, increased expression of CDKN1B, a tumor suppressor that prevents the activation of the cyclin-D/CDK4 complex, and also reduced expression of cyclin-D (CCND1) itself.XP-524 showed increased potency and superior tumoricidal activity than the benchmark BET inhibitor JQ-1 in vitro, with comparable efficacy to higher-dose JQ-1 combined with the EP300/CBP inhibitor SGC-CBP30.XP-524 prevented KRAS-induced, neoplastic transformation in vivo and extended survival in two transgenic mouse models of aggressive PDAC. |
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References | 1. Yangfeng Li, et al. J Med Chem. 2020 Jul 9;63(13):7186-7210. 2. Principe DR, et al. Proc Natl Acad Sci U S A. 2022 Jan 25;119(4):e2116764119. |
Molecular Formula | C30H28N6O3S |
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Molecular Weight | 552.653 |