MLT-231
目录号 : GC62611
MLT-231 是一种高效、高选择性的变构 MALT1 抑制剂，IC50 为 9 nM。MLT-231 特异性地阻止内源性 BCL10 断裂，IC50 为 160 nM。MLT-23 在 ABC-DLBCL 型异种移植模型中具有抗肿瘤活性。
Cas No.:2682102-10-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
MLT-231 is a potent, highly selective allosteric MALT1 Inhibitor with an IC50 of 9 nM. MLT-231 specifically prevents endogenous BCL10 cleavage with IC50 of 160 nM. MLT-231 shows antitumor activity in an ABC-DLBCL type xenograft model in mouse[1].
MLT-231 (19.5-10000 nM) inhibits the proliferation of OCI-Ly3 cells. MLT-231 (50-5000 nM; 24 hours) leads to accumulation of the uncleaved form of its substrates CYLD, BCL10, and RELB while expression of the NF-κB target gene IRF4 is suppressed[1].
MLT-231 (10-100 mg/kg; p.o.; bid schedule for 2 weeks) displays in vivo efficacy in the ABC-DLBCL xenograft model[1].MLT-231 (1 mg/kg; i.v.; BALB/c mice) treatment shows the CL, t1/2, and Vss are 11 mL/min/kg, 1.9 hours, and 1.5 L/kg, respectively[1].MLT-231 (1 mg/kg; i.v.; Sprague-Dawley rats) treatment shows the CL, t1/2, and Vss are 41 mL/min/kg, 3.2 hours, and 9.4 L/kg, respectively[1].MLT-231 (3 mg/kg; p.o.; BALB/c mice) treatment shows the AUC0-24, Cmax and F are 3096 nM/h, 549 nM, and 99%, respectively[1].MLT-231 (3 mg/kg; p.o.; Sprague-Dawley rats) treatment shows the AUC0-24, Cmax and F are 547 nM/h, 46 nM, and 61%, respectively.
[1]. Pissot Soldermann C, et al. Discovery of Potent, Highly Selective, and In Vivo Efficacious, Allosteric MALT1 Inhibitors by Iterative Scaffold Morphing [published online ahead of print, 2020 Nov 30]. J Med Chem. 2020;10.1021/acs.jmedchem.0c01245.
| Cas No. | 2682102-10-7 | SDF | |
| 分子式 | C19H19ClF3N7O2 | 分子量 | 469.85 |
| 溶解度 | DMSO : 110 mg/mL (234.12 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1283 mL | 10.6417 mL | 21.2834 mL |
| 5 mM | 0.4257 mL | 2.1283 mL | 4.2567 mL |
| 10 mM | 0.2128 mL | 1.0642 mL | 2.1283 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Discovery of Potent, Highly Selective, and In Vivo Efficacious, Allosteric MALT1 Inhibitors by Iterative Scaffold Morphing
J Med Chem 2020 Dec 10;63(23):14576-14593.PMID:33252239DOI:10.1021/acs.jmedchem.0c01245
MALT1 plays a central role in immune cell activation by transducing NF-κB signaling, and its proteolytic activity represents a key node for therapeutic intervention. Two cycles of scaffold morphing of a high-throughput biochemical screening hit resulted in the discovery of MLT-231, which enabled the successful pharmacological validation of MALT1 allosteric inhibition in preclinical models of humoral immune responses and B-cell lymphomas. Herein, we report the structural activity relationships (SARs) and analysis of the physicochemical properties of a pyrazolopyrimidine-derived compound series. In human T-cells and B-cell lymphoma lines, MLT-231 potently and selectively inhibits the proteolytic activity of MALT1 in NF-κB-dependent assays. Both in vitro and in vivo profiling of MLT-231 support further optimization of this in vivo tool compound toward preclinical characterization.