2. PROTAC MAPK/ERK Pathway GPCR/G Protein Apoptosis Cell Cycle/DNA Damage
  3. PROTACs Ras Apoptosis PERK p38 MAPK Caspase TNF Receptor
  4. MCB-36

MCB-36 是一种能招募 VHL 蛋白的泛 KRAS PROTAC 降解剂，而不影响 KRAS 的转录。MCB-36 对 HRAS 和 NRAS 蛋白水平的影响极小。MCB-36结合 G12D、G12C、G12V 和野生型 KRAS 的 GDP 负载状态，其 Kd ≈ 1 pM。MCB-36 降低 p-ERK 水平，诱导细胞凋亡 (apoptosis)。MCB-36 有效抑制 KRASG12C 耐药的癌细胞，重塑肿瘤免疫微环境。MCB-36 可用于结直肠癌和肺癌的研究 (Pink: 靶蛋白配体; Blue: E3 连接酶 (HY-112078); Black: 连接子 (HY-W091879))。

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

MCB-36

MCB-36 Chemical Structure

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 是否有货
50 mg   询价  
100 mg   询价  
250 mg   询价  

* Please select Quantity before adding items.

Customer Review

MCB-36 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

查看 Ras 亚型特异性产品:

查看所有亚型
K-Ras H-Ras N-Ras Ras

查看 p38 MAPK 亚型特异性产品:

查看所有亚型
p38 MAPK p38α p38β MAPK13 p38δ p38γ

查看 Caspase 亚型特异性产品:

查看所有亚型
Caspase 1 Caspase 2 Caspase 3 Caspase 4 Caspase 5 Caspase 6 Caspase 7 Caspase 8 Caspase 9 Caspase 10 Caspase 12 Caspase Caspase 11 Caspase-13

查看 TNF Receptor 亚型特异性产品:

查看所有亚型
TNFRSF1A/CD120a TNFRSF4 TNFRSF5/CD40 TNFRSF6/Fas/CD95 TNFRSF7/CD27 TNFRSF8/CD30 TNFRSF9/4-1BB/CD137 TNFRSF12A/TWEAK TNFRSF16/NGF Receptor/CD271 TNFRSF18/GITR/CD357

  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

MCB-36 is a VHL-recruiting pan-KRAS PROTAC degrader without affecting KRAS transcription. MCB-36 exhibits minimal effects on HRAS and NRAS protein levels. MCB-36 binds to the GDP-loaded state of G12D, G12C, G12V, and wild-type KRAS with high affinities Kd ≈ 1 pM). MCB-36 decreases p-ERK levels, leading to cell apoptosis. MCB-36 effectively suppress KRASG12C inhibitor-resistant cancer cells and remodel the tumor immune microenvironment. MCB-36 can be used for the study of colorectal cancer and lung cancer (Pink: Target protein ligand; Blue: E3 ligand (HY-112078); Black: Linker (HY-W091879))[1].

IC50 & Target[1]

KRas G12C

 

KRas G12D

 

KRas G12V

 

KRAS G13D

 

K-Ras WT

 

Caspase 3

 

体外研究
(In Vitro)

MCB-36 (1 nM-100 μM, 5 days) 对KRAS 依赖性癌细胞 (如PC-1 (G12D)、H358 (G12C)、LS180 (G12V)、HCT116 (G13D) 等) 具有显著的抗增殖作用 (测试的 30 种细胞系中有 24 种的平均 IC50 约为1 μM)，同时对正常细胞 (hTERT-HPNE、NCM460) 和非 KRAS 依赖性细胞无影响 (IC50 > 10 μM)[1]。
MCB-36 (0-10 μM, 0-72 h) 在所有测试的细胞系中均能有效降解 KRAS 蛋白、降低 p-ERK 水平并诱导细胞死亡，包括表达 KRASG12C、KRASG12C/Y96C 和 KRASG12C/H95D 的 MIA PaCa-2 细胞[1]。
MCB-36 (0-2.5 μM, 6 days) 抑制 KRAS 突变型结直肠癌类器官的生长，同时伴随 MAPK 信号通路成分的丰度降低和凋亡标志物的升高[1]。
MCB-36 显著上调从 CT26 肿瘤中分离的 CD45+免疫细胞中的 TNF-α 应答通路，并增加效应性 CD8+ T 细胞的丰度[1]。

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

MCB-36 相关抗体:

Western Blot Analysis[1]

Cell Line: Caco-2 (WT), Capan-2 (G12V), H358 (G12C), AsPC-1 (G12D) cells
Concentration: 0, 0.1, 1 and 10 μM
Incubation Time: 0, 3, 6, 12, 24, 48 h
Result: Dose- and time- dependently degraded KRAS.
Dose- and time- dependently decreased p-ERK, cleaved caspase-3, and cleaved PARP.

Western Blot Analysis[1]

Cell Line: MIA PaCa-2 (G12C), MIA PaCa-2 (G12C/Y96C) and MIA PaCa-2 (G12C/H95D)
Concentration: 100 nM
Incubation Time: 0, 1, 3, 6, 12, 24, 36, 48, 72 h
Result: Inhibited p-ERK levels, induced cell death and retained their potency over at least 36 h.

Western Blot Analysis[1]

Cell Line: KRAS-mutant colorectal cancer organoids
Concentration: 0, 1.25 and 2.5 μM
Incubation Time: 6 days
Result: Decreased p-ERK, cleaved caspase-3, and cleaved PARP.
体内研究
(In Vivo)

MCB-294 (10 mg/kg, i.p., 单次剂量) 在小鼠体内具有生物可利用性，且在治疗 6 小时后可降低 KRAS 和 p-ERK 水平[1]。
MCB-294 (60 mg/kg, i.p., 每日 2 次, 共 1-21 天) 有效抑制 KRASG12C 耐药的癌细胞，并重塑小鼠的肿瘤免疫微环境[1]。

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

Animal Model: Patient-derived xenograft (PDX) model induced by colorectal carcinoma harboring a KRASG12C mutation (PDX A02), and lung adenocarcinoma harboring a KRASG12V mutation (PDX A03) established in four- to five-week-old male BALB/c mice[1]
Dosage: 60 mg/kg
Administration: Intraperitoneal administration (i.p.), twice daily, for 16 days
Result: Significantly reduced tumor volume and weight in the PDX A02 and PDX A03 xenograft models. Showed a dramatic decrease in KRAS and Ki67 expression from a cohort of treated mice. No signs of overt toxicity were observed, as mouse body weight maintained stable.
Animal Model: CT26 induced immunoregulation model established in six- to eight-week-old male BALB/c nude mice[1]
Dosage: 60 mg/kg
Administration: Intraperitoneal administration (i.p.), twice daily, for 2 days
Result: Increased the abundance of effector CD8+ T cells, IFN-γ, TNF-α and Ki67.
Enhanced the efficacy of anti-PD-1 therapy.
分子量

1100.32

Formula

C60H71F2N9O7S
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

MCB-36 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:

MCB-36MCB36MCB 36PROTACsRasApoptosisPERKp38 MAPKCaspaseTNF ReceptorProtein kinase R-like endoplasmic reticulum kinasePKR-like endoplasmic reticulum kinaseTumor Necrosis Factor ReceptorTNFRKRAS signalingcancer therapeuticsdegraderimmune evasiononcogenic KRASpan-KRAS inhibitortargeted protein degradationtherapy resistancetumor immune microenvironmentInhibitorinhibitorinhibit

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：
MCB-36
目录号：
HY-176786
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