2. PROTAC Neuronal Signaling
  3. PROTACs Huntingtin
  4. PROTAC mHTT Degrader-1

PROTAC mHTT Degrader-1 是一种能够穿透血脑屏障的突变亨廷顿蛋白 (mHTT) PROTAC 降解剂。PROTAC mHTT Degrader-1 特异性识别致病的 mHTT 聚集体，并招募 Cereblon (CRBN)，从而诱导 mHTT 发生泛素化并被蛋白酶体降解。PROTAC mHTT Degrader-1 减轻了 mHTT 诱导的细胞毒性和神经炎症。在 R6/2 亨廷顿舞蹈病小鼠模型中，PROTAC mHTT Degrader-1 降低了脑内蛋白聚集水平，改善了动物的体重、运动协调性及存活率。PROTAC mHTT Degrader-1 可用于亨廷顿病及其他神经退行性疾病的 PROTAC 疗法的研究。
(粉色: Huntingtin 配体 (HY-181897)；蓝色: Cereblon 配体 (HY-41547)；黑色: 连接子 (HY-W007545))。

MCE 的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

我们将采用定制合成服务的方式为您快速提供所需产品和技术服务

PROTAC mHTT Degrader-1

PROTAC mHTT Degrader-1 Chemical Structure

CAS No. : 2919475-43-5

1.  客户无需承担相应的运输费用。

2.  同一机构（单位）同一产品试用装仅限申领一次，同一机构（单位）一年内

     可免费申领三个不同产品的试用装。

3.  试用装只面向终端客户。

规格 价格 是否有货 数量
5 mg ￥7904
8 - 10 周
10 mg 询价 8 - 10 周
25 mg 询价 8 - 10 周
50 mg   询价  
100 mg   询价  

* Please select Quantity before adding items.

Customer Review

PROTAC mHTT Degrader-1 相关抗体

Top Publications Citing Use of Products

查看 PROTACs 亚型特异性产品:

查看所有亚型
von Hippel-Lindau (VHL) Cereblon MDM2 cIAP1

  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

PROTAC mHTT Degrader-1 is a blood-brain barrier-penetrant mutant huntingtin (mHTT) PROTAC degrader. PROTAC mHTT Degrader-1 specifically recognizes pathogenic mHTT aggregates and recruits Cereblon (CRBN), thereby inducing ubiquitination and proteasomal degradation of mHTT. PROTAC mHTT Degrader-1 alleviates mHTT-induced cytotoxicity and neuroinflammation. In the R6/2 Huntington's disease mouse model, PROTAC mHTT Degrader-1 reduces cerebral protein aggregation levels and improves body weight, motor coordination and survival rate of animals. PROTAC mHTT Degrader-1 can be used for research on PROTAC therapies for Huntington's disease and other neurodegenerative diseases[1]. (Pink: Huntingtin ligand (HY-181897); Blue: Cereblon ligand (HY-41547); Black: linker (HY-W007545)).

IC50 & Target

Cereblon

 

体外研究
(In Vitro)

PROTAC mHTT Degrader-1 (PROTAC 2′) (1 μM；22 h) 可显著降低表达 HTT (Q)109-eYFP 的 N2a 细胞中 mHTT 聚集体阳性细胞比例与不溶性 mHTT 聚集体水平，对可溶性 mHTT 水平无显著影响；可降低细胞内 DNA 损伤标志物 p-H2A.X (Ser139) 的水平，抑制 mHTT 诱导的细胞凋亡通路激活[1]。
PROTAC mHTT Degrader-1 (PROTAC 2′) (1 μM；22 h) 可减少细胞内 mHTT 寡聚体比例，实现对可溶性寡聚体和不溶性聚集体的同步靶向降解；其降解作用可被蛋白酶体抑制剂 MG132 显著逆转，证实其通过泛素 - 蛋白酶体系统发挥作用[1]。
PROTAC 2′ (0.01-10 μM；22 h) 可剂量依赖性地选择性降解表达 HTT (Q)109-eYFP 的 N2a 细胞中的 mHTT 聚集体，对非致病性的 HTT (Q)25-eYFP 水平无明显影响[1]。
PROTAC 2′ (1 μM；48 h) 可显著提升表达 HTT (Q)109-eYFP 的 N2a 细胞的活力，有效缓解 mHTT 诱导的神经细胞毒性[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

PROTAC mHTT Degrader-1 相关抗体:

Cell Viability AssayWestern Blot AnalysisCell Proliferation AssayApoptosis AnalysisCell Cytotoxicity AssayCell Cycle AnalysisRT-PCRCell Autophagy AssayImmunofluorescenceCell Differentiation AssayCell Invasion AssayCell Migration Assay Real Time qPCRELISA Assay[1]

Cell Line: Mouse neuroblastoma N2a cells transfected with HTT(Q)109-eYFP or HTT(Q)25-eYFP plasmid
Concentration: 0.01 μM, 0.1 μM, 1 μM, 10 μM
Incubation Time: 22 h
Result: Degraded insoluble HTT(Q)109-eYFP aggregates in a dose-dependent manner, while it exerted negligible effect on the level of soluble HTT(Q)109-eYFP and nonpathogenic HTT(Q)25-eYFP across all tested concentrations.
Reduced the level of DNA damage marker phosphor-H2A.X (Ser139) at 1 μM, and relieved the mHTT-induced cellular apoptosis pathway activation.
体内研究
(In Vivo)

PROTAC mHTT Degrader-1 (PROTAC 2′) (3 mg/kg；皮下注射；单次；给药后观察 6 h) 野生型 B6CBA 小鼠模型，可穿透血脑屏障，在给药后 6 h 内可在小鼠脑组织中持续检测到，平均浓度维持在约 1.96 ppb[1]。

PROTAC mHTT Degrader-1 (3 mg/kg/ 周；皮下注射；每周 1 次；连续给药 5 周) 在野生型 B6CBA 小鼠模型中，长期给药后小鼠体重、大脑皮层厚度、纹状体体积与对照组无显著差异，血清肝肾功能指标无异常，无明显肝、肾、脑组织毒性[1]。
PROTAC mHTT Degrader-1 (3 mg/kg/ 周；皮下植入渗透泵持续给药；持续输注；给药 4 周) 在 B6CBA-R6/2 亨廷顿病小鼠模型中，可显著延缓模型小鼠体重下降，改善运动协调能力与自发探索行为，延长生存期；同时可降低小鼠脑内 mHTT 聚集体水平与神经炎症，缓解皮层与纹状体萎缩，部分恢复神经元功能[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Wild-type (WT) B6CBA mice, 6 weeks of age at administration, n=9 per time point[1]
Dosage: 3 mg/kg/week
Administration: subcutaneous (SC) injection once a week for 5 consecutive weeks
Result: No structural abnormalities were observed in the cortical thickness, striatal volume of the brain, or the morphology of liver and kidney tissues in PROTAC 2′-treated mice.
There were no significant differences in serum levels of liver function markers (AST, ALT) and kidney function markers (BUN, CRE), indicating no evident hepatotoxicity or nephrotoxicity of the compound after long-term low-dose administration.
Animal Model: B6CBA-Tg(HDexon1)62Gpb/1J (R6/2) transgenic Huntington’s disease mice and wild-type B6CBA mice, 6 weeks of age at the start of administration[1]
Dosage: 3 mg/kg/week
Administration: subcutaneously implanted osmotic pumps for 4 weeks
Result: Markedly delayed the progressive weight loss of R6/2 mice, and maintained higher body weight of the model animals until 11 weeks of age.
Significantly improved the motor coordination of R6/2 mice in the rotarod assay from 10 to 13 weeks of age, and increased the rearing frequency of the model mice in the cylinder assay at 14 weeks of age.
Significantly extended the survival of R6/2 mice: 50% of treated mice survived to 16 weeks and 35% survived to 17 weeks, while all vehicle-treated R6/2 mice died by 15 weeks of age.
分子量

613.66

Formula

C33H35N5O7
CAS 号
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.
纯度 & 产品资料
参考文献

PROTAC mHTT Degrader-1 相关分类

  • 摩尔计算器

  • 稀释计算器

The molarity calculator equation

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

质量   浓度   体积   分子量 *
= × ×

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

浓度 (start) × 体积 (start) = 浓度 (final) × 体积 (final)
× = ×
C1   V1   C2   V2
Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

PROTAC mHTT Degrader-12919475-43-5PROTAC mHTT Degrader1PROTAC mHTT Degrader 1PROTACsHuntingtinaggregated mutant huntingtinE3 ubiquitin ligasewild-type huntingtinmHTTneuroinflammationcereblonCRBNHuntington’s diseaseblood-brain barrierR6/2 mouse modelsInhibitorinhibitorinhibit

您最近查看的产品:

Your information is safe with us. * Required Fields.

   产品名称：

  

* 需求量：

* 客户姓名：

 

* Email：

* 电话：

 

* 公司或机构名称：

   留言给我们：

Bulk Inquiry

Inquiry Information

产品名称：
PROTAC mHTT Degrader-1
目录号：
HY-181879
需求量：

Request for HNMR Report

Please fill out this form to request the QC report. We will send it to your Email address shortly.

Your information is safe with us. * Required Fields.

   产品名称：

  

* Lot #：

* 客户姓名：

 

* Email：

   电话：

 

* 部门：

* 公司或机构名称：

 

   留言给我们：

Request for HNMR Report

We have received your request and will respond to you as soon as possible.

嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z