2. Epigenetics TGF-beta/Smad Stem Cell/Wnt Neuronal Signaling
  3. Histone Demethylase TGF-beta/Smad Notch
  4. TAS1440

TAS1440 是一种口服有效的 LSD1/KDM1A 抑制剂，对人源靶点的 IC50 为 4.8 nM。TAS1440 以非共价方式结合 LSD1 的组蛋白 H3 结合口袋，抑制其去甲基化酶活性，并破坏其与 INSM1 和 SMAD2 形成的抑制性复合物。TAS1440 通过转录重编程激活具有肿瘤抑制作用的 TGF-β 和 NOTCH 信号通路。TAS1440 可用于小细胞肺癌 (尤其是 SCLC-A 亚型) 的研究。

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

TAS1440

TAS1440 Chemical Structure

CAS No. : 2098585-77-2

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

Other Forms of TAS1440:

TAS1440 相关抗体

Top Publications Citing Use of Products

查看 Histone Demethylase 亚型特异性产品:

查看所有亚型
KDM1/LSD1 KDM2 KDM3 KDM4 KDM5 KDM6 KDM7

  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

TAS1440 is an orally active LSD1/KDM1A inhibitor with a human IC50 of 4.8 nM. TAS1440 non-covalently binds to the histone H3-binding pocket of LSD1, inhibiting demethylase activity and disrupting repressive complexes with INSM1 and SMAD2. TAS1440 activates tumor-suppressive TGF-β and NOTCH signaling pathways via transcriptional reprogramming. TAS1440 can be used for the research of small cell lung cancer, specifically the SCLC-A subtype[1].

IC50 & Target[1]

KDM1/LSD1

4.8 nM (IC50)

体外研究
(In Vitro)

TAS1440 是一种高选择性、组蛋白 H3 竞争性的纯化重组人源 LSD1 抑制剂，其 IC50 为 4.8 nM，对 LSD2、MAO-A、MAO-B 或其他多种表观遗传酶无显著活性[1]。
TAS1440 (0-7500 nM；8 天) 可选择性抑制 SCLC-A 细胞系的增殖，在 NCI-H1417、NCI-H510A、NCI-H146 和 COR-L51 细胞中的活性最强，且在这些敏感模型中表现出比共价 LSD1 抑制剂更强的抗增殖活性[1]。
TAS1440 (300 nM；1-7 天) 可诱导 SCLC 细胞系发生转录重编程，激活具有肿瘤抑制作用的 TGF-β 和 NOTCH 通路，并抑制神经内分泌基因的表达，其中对 TAS1440 敏感的 SCLC-A 细胞系的变化最为显著[1]。
TAS1440 (300 nM；30 分钟-5 天) 可通过诱导 SMAD2 磷酸化、NOTCH1 上调及通路活性组分的核蓄积，激活 SCLC-A 细胞系中的 TGF-β 和 NOTCH 信号通路；同时，其破坏 INSM1-LSD1 与 SMAD2-LSD1 蛋白复合物的效果优于共价 LSD1 抑制剂[1]。
TAS1440 (300 nM；5 天) 可在 SCLC-A 细胞系中诱导全局表观遗传重编程，增加转录起始位点 (TSSs) 处的活性组蛋白标记 (H3K4me1、H3K4me2、H3K27ac)，并促进 INSM1 和 SMAD2 与抑癌的 NOTCH 及 TGF-β 通路基因启动子结合[1]。
TAS1440 (100-3000 nM；7 天) 在 SCLC-A 细胞系中的抗增殖作用与转录效应依赖于 LSD1 的表达及催化活性，而其破坏 INSM1/SMAD2-LSD1 复合物的能力则不依赖于 LSD1 的催化功能[1]。
TAS1440 (300 nM；2 小时-10 天) 的抗增殖作用、转录重编程以及对 SCLC-A 细胞系中 TGF-β/NOTCH 信号通路的激活依赖于 INSM1[1]。

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

TAS1440 相关抗体:

Cell Proliferation Assay[1]

Cell Line: 19 small cell lung cancer (SCLC) cell lines stratified into SCLC-A, SCLC-N, and SCLC-P subtypes
Concentration: 7500 nM
Incubation Time: 8 days
Result: Showed the strongest growth suppression in SCLC-A cell lines compared to SCLC-N and SCLC-P subtypes.
Exhibited the lowest IC50 values in NCI-H1417, NCI-H510A, NCI-H146, and COR-L51 SCLC-A cells.
Exhibited greater potency than covalent LSD1 inhibitors in sensitive SCLC-A lines, as covalent comparators often had IC50 values ≥1,000 nM or were right-censored at the 7,500 nM testing limit.
Showed broadly similar inhibition patterns to another H3-competitive inhibitor (CC-90011) but greater potency in the most sensitive SCLC-A lines.
体内研究
(In Vivo)

TAS1440 (16.7-50 mg/kg/day；口服；每日给药；持续 3 周) 可显著抑制多种 SCLC-A 皮下异种移植模型的肿瘤生长，并在异种移植肿瘤中激活具有抑瘤作用的 NOTCH/TGF-β 信号通路[1]。
TAS1440 (50 mg/kg/天；口服；每日给药；持续 3 周) 可显著抑制 INSM1 野生型而非 INSM1 敲除型 NCI-H146 SCLC-A 异种移植瘤的生长，表明其体内疗效依赖于 INSM1[1]。
TAS1440 (50 mg/kg/天；口服；每日给药；持续 4 周) 在原位 NCI-H146 SCLC-A 异种移植模型中可使肺部肿瘤负荷降低 67%[1]。

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

Animal Model: C.B-17 SCID mice (male, 6-week-old, subcutaneously injected with NCI‑H1417, NCI‑H146, NCI‑H510A, COR-L51 and NCI-H146 INSM1-KO cells)[1]
Dosage: 16.7 mg/kg/day; 50 mg/kg/day
Administration: p.o.; daily; 3 weeks
Result: Significantly reduced tumor growth in NCI-H1417 xenografts compared with vehicle at 16.7 and 50 mg/kg/day.
Significantly reduced tumor growth in NCI-H146, NCI-H510A, and COR-L51 xenografts compared with vehicle at 50 mg/kg/day.
Upregulated NOTCH1 and increased phosphorylated SMAD2 (pSMAD2) in xenograft tumors.
Induced NOTCH/TGF-β pathway genes (NOTCH1, HES1, TGFB2, TGFBR2, ID3) and reduced ASCL1 and DLL3 in xenograft tumors.
Animal Model: C.B-17 SCID mice (male, 6-week-old, subcutaneously injected with NCI‑H1417, NCI‑H146, NCI‑H510A, COR-L51 and NCI-H146 INSM1-KO cells)[1]
Dosage: 50 mg/kg/day
Administration: p.o.; daily; 3 weeks
Result: Significantly reduced tumor growth in INSM1-wild-type NCI-H146 xenografts compared with vehicle.
Had no significant effect on tumor growth in INSM1-knockout NCI-H146 xenografts.
Animal Model: C.B-17 SCID mice (male, 6-week-old, subcutaneously injected with NCI‑H1417, NCI‑H146, NCI‑H510A, COR-L51 and NCI-H146 INSM1-KO cells)[1]
Dosage: 50 mg/kg/day
Administration: p.o.; daily; 4 weeks
Result: Reduced pulmonary tumor area by 67% compared with vehicle, as measured by micro-CT volumetric quantification.
分子量

475.53

Formula

C28H27F2N3O2
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

TAS1440 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:

TAS14402098585-77-2TAS 1440TAS-1440Histone DemethylaseTGF-beta/SmadNotchTransforming growth factor betaNOTCH signaling pathwaysINSM1histone H3NCI-H1417SMAD2Lysine-specific histone demethylase 1ASCLC-A subtypeTGF-β signaling pathwayssmall cell lung cancerLSD1/KDM1AInhibitorinhibitorinhibit

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：
TAS1440
目录号：
HY-183067
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