Alobresib (GS-5829)

製品コードS8961 バッチS896101

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
化学式

C26H23N5O2
分子量 437.49 CAS No. 1637771-14-2
Solubility (25°C)* 体外 DMSO 87 mg/mL (198.86 mM)
Ethanol 11 mg/mL (25.14 mM)
Water ˂1 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Alobresib (GS-5829) is a novel BET inhibitor that represents a highly effective therapeutics agent against recurrent/chemotherapy-resistant USC-overexpressing c-Myc. Alobresib (GS-5829) inhibits CLL cell proliferation and induces leukemia cell apoptosis through deregulation of key signaling pathways, such as BLK, AKT, ERK1/2, and MYC. Alobresib (GS-5829) also inhibits NF-κB signaling.
in vitro

In-vitro experiments demonstrates high sensitivity of USC cell-lines to the exposure to GS-5829 causing a dose-dependent decrease in the phosphorylated levels of c-Myc and a dose-dependent increase in caspase activation (apoptosis).[1] GS-5829 inhibits CLL cell proliferation and induces leukemia cell apoptosis through deregulation of key signaling pathways, such as BLK, AKT, ERK1/2, and MYC. IκBα modulation indicates that GS-5829 also inhibits NF-κB signaling. GS-5829-induced apoptosis results from an imbalance between positive (BIM) and negative regulators (BCL-XL) of the intrinsic apoptosis pathway.[2]
in vivo

GS-5829 has impressive activity against USC primary tumors as well as USC xenografts. Assessment of c-Myc expression in tumors exposed to the GS-5829 demonstrates down-regulation of both total and phospho c-Myc proteins. GS-5829 demonstrates excellent bioavailability after oral administration and is significantly more effective than JQ1 at the doses used in comparative experiments in vivo against USC xenografts. Clinical studies with GS-5829 in USC patients harboring disease resistant to standard salvage chemotherapy are warranted.[1]

プロトコル(参考用のみ)

細胞アッセイ 細胞株 PBMC, MEC-1
濃度 100 nM, 200 nM, 400 nM, 800 nM
反応時間 72 h, 24 h
実験の流れ

TACS XTT cell proliferation/viability assay (Trevigen) is performed according to the manufacturer’s instructions on MEC-1 cells treated with GS-5829 or the BCR signaling inhibitors for 72 h. Half-maximal inhibitory concentrations (IC50) are calculated using Prism 6 or 7 based on technical triplicate measurements.
動物実験 動物モデル female CB17/lcrHsd-Prkd/scid mice bearing USC-ARK1 or USC-ARK2 xenograft
投薬量 20 mg/kg, 10 mg/kg
投与方法 Oral gavage

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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