产品说明书

Mivebresib

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Chemical Structure| 1445993-26-9 同义名 : ABBV-075
CAS号 : 1445993-26-9
货号 : A414117
分子式 : C22H19F2N3O4S
纯度 : 99%+
分子量 : 459.466
MDL号 : MFCD30377200
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(228.53 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • BET
描述 Mivebresib is a potent and selective inhibitor of the bromodomain and extra terminal domain family of proteins. It binds to the bromodomains of BRD2/4/T with Ki values of 1-2.2nM. It also exhibits 10-fold weaker potency for BRD3 with a Ki value of 12.2nM. Mivebresib is highly selective for 18 bromodomain proteins with Kd values >1μM ( >600-fold selectivity versus BRD4). It displayed moderate activity towards CREBBP with a Kd value of 87μM (54-fold selectivity versus BRD4). Mivebresib showed robust single agent activity in cancer cell lines derived from lymphomas, leukemia, and solid tumors. It disrupted cell cycle control of cancer cells, inhibiting apoptosis and oncogenesis[3]. Mivebresib inhibited DHT-stimulated transcription of androgen receptor (AR) target genes without affecting the protein expression of AR. It disrupted DHT-stimulated recruitment of BRD4 to gene regulatory regions co-occupied by AR. Mivebresib also inhibited MYC and TMPRSS2-ETS fusion proteins with high potency[4]. In flank xenograft mouse models, mivebresib exhibited potent anti-tumor activity comparable or superior to standard-of-care agents[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.18mL

0.44mL

0.22mL

10.88mL

2.18mL

1.09mL

21.76mL

4.35mL

2.18mL
参考文献

[1]Bui MH, Lin X, et al. Preclinical characterization of BET family bromodomain inhibitor ABBV-075 suggests combination therapeutic strategies. Cancer Res. 2017 Apr 17. pii: canres.1793.2016.

[2]Lin X, Huang X, et al. HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues. Mol Cancer Ther. 2017 Feb;16(2):388-396.

[3]Abstract 4718: ABBV-075, a novel BET family bromodomain inhibitor, represents a promising therapeutic agent for a broad spectrum of cancer indications

[4]Abstract 4694: ABBV-075, a novel BET family inhibitor, disrupts critical transcription programs that drive prostate cancer growth to induce potent anti-tumor activity in vitro and in vivo