AGB1

发表于由

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

AGB1 

AGB1 是一种高选择性的有效 B&H-PROTAC 降解剂。AGB1 降解 Ab:Brd4BD2 L387A 和 Ab: BromoTag-Brd2，pDC50 分别为 7.8 和 7.9。AGB1 对 VHL 具有亲和力，Kd=125 nM。AGB1 在小鼠体内具有良好的药代动力学特征 （DC50, 6 h 约为 13 nM)。

AGB1

AGB1 Chemical Structure

规格 是否有货
100 mg   询价  
250 mg   询价  
500 mg   询价  

* Please select Quantity before adding items.

生物活性

AGB1 is a fast, highly selective, and potent bump-and-hole (B&H)-PROTAC degrader for BromoTag. AGB1 exhibits degradation for Ab:Brd4BD2 L387A and Ab: BromoTag-Brd2 with pDC50s of 7.8 and 7.9. AGB1 exhibits binary affinity to VHL (Kd=125 nM). AGB1 exhibits favorable pharmacokinetic profile in mice with the DC50, 6 h of ∼13 nM[1].

IC50 & Target

VHL

 

体外研究
(In Vitro)

AGB1 not only forms a strong, cooperative ternary complex between VHL and the BromoTag (Brd4BD2 L387A) but also completely degrades BromoTagged target proteins with low nanomolar potency and exquisite selectivity over the native wild-type BET proteins at the proteome-wide level[1].
AGB1 is not cytotoxic in several cancer relevant cell lines, further exemplifying its superior selectivity over off-target endogenous BET proteins[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究
(In Vivo)

AGB1 has also shown excellent plasma stability and acceptable pharmacokinetic (PK) profile in mice. AGB1 has good PK profiles in mice for both intravenous (IV) and subcutaneous (SC) 5 mg/kg injections. AGB1 exhibits short elimination half-life (mouse 1.49 h) due to relatively low clearance (47.2 mL/min/kg) following intravenous administration (5.0 mg/kg). AGB1 exhibits short elimination half-life (mouse 1.65 h) due to the Cmax (0.700 μM) and Tmax (0.500 h) following subcutaneous injection (5.0 mg/kg).AGB1 maintains a plasma concentration above its BromoTag-Brd2 DC50, 6 h of ∼13 nM when dosed at 5 mg/kg for ∼4 h IV injection and for >8 h SC injection[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Six- to eight-week-old C57BL/6 male mice[1]
Dosage: 5 mg/kg (Pharmacokinetic Analysis)
Administration: Administered IV injections into the tail vein of nine mice; or administered via SC injection in nine mice. The animals were restrained manually at the designated time points (0.083, 0.25, 0.5, 1, 2, 4, and 8 h); approximately, 110 μL of blood sample was collected.
Result: A relatively low clearance rate (CL) of 47.2 mL/min/kg and good half-lives (T1/2) of 1.49 and 1.65 h in IV and SC, respectively.

分子量

1031.68

Formula

C51H63ClN8O9S2
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献

  • [1]. Adam G Bond, et al. Development of BromoTag: A “Bump-and-Hole”-PROTAC System to Induce Potent, Rapid, and Selective Degradation of Tagged Target Proteins. J Med Chem. 2021 Oct 28;64(20):15477-15502.

所有产品仅用作科学研究或药证申报，我们不为任何个人用途提供产品和服务