2. PROTAC Stem Cell/Wnt Cell Cycle/DNA Damage Apoptosis NF-κB Metabolic Enzyme/Protease
  3. Molecular Glues Casein Kinase MDM-2/p53 MALT1
  4. INNO-220

INNO-220 是一种具有口服活性，依赖 CRBN 的 靶向 CK1α 的分子胶降解剂。INNO-220 通过降解 CK1α 诱导细胞周期停滞在 G0/G1 期并引发细胞凋亡 (Apoptosis)。INNO-220 破坏 CARD11/BCL10/MALT1 复合物的组装和功能，从而抑制 CARD11 发生激活突变的刺激 T 细胞和淋巴瘤细胞中的 NF-κB 信号通路。INNO-220 为淋巴瘤研究提供了新方向。

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INNO-220

INNO-220 Chemical Structure

CAS No. : 3032576-92-1

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INNO-220 相关抗体

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CK1 CK2

  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

INNO-220 is an orally active, CRBN-dependent molecular glue degrader targeting CK1α. INNO-220 induces cell cycle arrest at G0/G1 phase and triggers apoptosis by degrading CK1α. INNO-220 disrupts the assembly and function of the CARD11/BCL10/MALT1 complex, thereby inhibiting NF-κB signaling in stimulated T cells and lymphoma cells that harbor an activating mutation in CARD11. INNO-220 provides a new direction for lymphoma research[1].

体外研究
(In Vitro)

INNO-220 (Compound INNO-220) (0.0001-10 μM, 72 h) 对野生型 p53 淋巴瘤细胞具有广谱抗增殖活性[1]。

INNO-220 (0.0001-10 μM, 24-72 h) 对 IL-2 的抑制作用依赖于 CRBN[1]。

INNO-220 (2-1250 nM, 24 h) 通过激活细胞凋亡途径并诱导细胞周期停滞在 G0/G1 期，抑制淋巴瘤细胞的生长[1]。

INNO-220 (50 nM, 8 h) 调控 OCI-Ly3 和 Z-138 细胞中的 p53/NF-κB 信号通路[1]。

INNO-220 (2-1250 nM, 6-24 h) 在 OCI-Ly3 cells, Z-138 cells, OCI-Ly19 cells 中通过降解 CK1α 激活 p53[1]。

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

INNO-220 相关抗体:

Cell Viability Assay[1]

Cell Line: 18 B-cell lymphoma cell lines, multiple wild-type p53 cell lines, DLBCL and MCL patients' cells
Concentration: 0.0001 μM, 0.001 μM, 0.01 μM, 0.1 μM, 1 μM, 10 μM
Incubation Time: 24 h, 72 h
Result: Significantly inhibited the viability of wild-type p53 lymphoma cell lines (OCI-Ly3 cells, OCI-Ly10 cells, TMD8 cells, OCI-Ly19 cells, Will-2 cells, Z-138 cells).
Significantly reduced the viability of primary patient cells.
Significantly inhibited IL-2 secretion, while having minimal effect on cell viability of PBMC and THLE-2 cells.
Had no inhibitory effect on IL-2 in CRBN knockout Jurkat cells.

Apoptosis Analysis[1]

Cell Line: OCI-Ly3 cells
Concentration: 2 nM, 10 nM, 50 nM, 250 nM, 1250 nM
Incubation Time: 24 h
Result: Induced apoptosis in a dose-dependent manner.
Cleaved PARP and Caspase 3/8/9 expression increased.

Cell Cycle Analysis[1]

Cell Line: OCI-Ly3 cells
Concentration: 2 nM, 10 nM, 50 nM, 250 nM, 1250 nM
Incubation Time: 24 h
Result: Significantly increased the proportion of cells in the G0/G1 phase and decreased the proportion in the S/G2/M phase.

Real Time qPCR[1]

Cell Line: OCI-Ly3 cells, Z-138 cells
Concentration: 50 nM
Incubation Time: 8 h
Result: Up-regulated the expression of p53 target genes (CDKN1A, BAX, MDM2) and down-regulated NF-κB target genes.

Western Blot Analysis[1]

Cell Line: OCI-Ly3 cells, Z-138 cells, MOLT-4 cells, OCI-Ly19 cells
Concentration: 2 nM, 10 nM, 50 nM, 250 nM, 1250 nM
Incubation Time: 6 h, 8 h, 24 h
Result: Dose-dependently degraded CK1α (DC50 = 3.8 nM in OCI-Ly3 cells, DC50 = 23.4 nM in Z-138 cells).
Activated the p53 pathway (upregulation of p53, p21, and MDM2), inhibited CBM complex assembly, and suppressed NF-κB signaling.
体内研究
(In Vivo)

INNO-220 (Compound INNO-220) (3-20 mg/kg, i.g, daily for 43 days) 可诱导 DLBCL 和 MCL 异种移植模型中的肿瘤消退并抑制 NF-κB 活性，且小鼠体重无显著变化，为淋巴瘤相关研究提供了新方向[1]。

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

Animal Model: DLBCL xenograft model established in nude male mice (4 weeks)[1]
Dosage: 3 mg/kg, 10 mg/kg, 20 mg/kg
Administration: Daily Oral gavage (i.g.), at the corresponding doses for 43 days.
Result: Significantly inhibited tumor growth at 20 mg/kg.
Degraded CK1α, upregulated p53 expression, and reduced Ki67 levels in tumor tissues.
分子量

400.43

Formula

C23H20N4O3
CAS 号
性状

固体

运输条件

Room temperature in continental US; may vary elsewhere.
储存方式
Powder -20°C 3 years
In solvent -80°C 6 months
-20°C 1 month
纯度 & 产品资料
参考文献

INNO-220 相关分类

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  • 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:

INNO-2203032576-92-1INNO220INNO 220Molecular GluesCasein KinaseMDM-2/p53MALT1mucosa associated lymphoid tissue lymphoma translocation gene 1DLBCL/MCL cellsCK1αlymphomaCRBNDLBCL/MCL xenograft modelInhibitorinhibitorinhibit

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