Alobresib (GS-5829)

製品コードS8961 バッチS896101

印刷

化学情報

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

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension

CMC-NA

≥5mg/ml

Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 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 this compound causing a dose-dependent decrease in the phosphorylated levels of c-Myc and a dose-dependent increase in caspase activation (apoptosis).^[1] It 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 this agent also inhibits NF-κB signaling. Its-induced apoptosis results from an imbalance between positive (BIM) and negative regulators (BCL-XL) of the intrinsic apoptosis pathway.^[2]
in vivo	Alobresib (GS-5829) has impressive activity against USC primary tumors as well as USC xenografts. Assessment of c-Myc expression in tumors exposed to this compound demonstrates down-regulation of both total and phospho c-Myc proteins. This chemical 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 this compound 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 this compound 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

参考

https://pubmed.ncbi.nlm.nih.gov/29941483/
https://pubmed.ncbi.nlm.nih.gov/31862959/

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。