MYLS22
(Synonyms: N-(1,5-二甲基-3-氧代-2-苯基-2,3-二氢-1H-吡唑-4-基)-3-甲基-1-苯基-1H-噻吩并[2,3-C]吡唑-5-甲酰胺) 目录号 : GC60260
MYLS22是视神经萎缩1(OPA1)的选择性抑制剂。MYLS22通过靶向内皮OPA1来抑制肿瘤生长,并通过影响NF-kB活性和血管生成基因表达来抑制血管生成。它具有抗血管生成和抗癌活性。
Cas No.:306959-01-3
Sample solution is provided at 25 µL, 10mM.
MYLS22 is a selective inhibitor of optic atrophy 1 (OPA1). MYLS22 inhibits tumor growth by targeting endothelial OPA1 and inhibits angiogenesis by affecting NF-kB activity and angiogenic gene expression. It has anti-angiogenic and anti-cancer activities [1-7].
MYLS22 (50μM) inhibits the growth of PANC-1 cells after 2 days and reduces cell migration after 72 hours [1]. MYLS22 (30μM, 72h) restores gefitinib-induced mitochondrial apoptosis in PC9M2 cells [3]. MYLS22 (50μM, 48h) significantly increased doxorubicin-induced cell killing and reduced doxorubicin-mediated mitochondrial elongation and OXPHOS [4]. MYLS22 (50μM, 24h), by inhibiting OPA1, reverses TIM-4-induced enhancement of OXPHOS and disrupts mitochondrial fusion, thereby attenuating lung cancer progression [5].
In a subcutaneous B16F10 mouse melanoma mode using C57BL6/J mice, MYLS22 (10mg/kg, ip, 6d) effectively inhibited melanoma proliferation and growth [2]. In a subcutaneous PC9M2 xenograft model using KSN/Slc mice, MYLS22 (25mg/kg, po, 18d) reversed the resistance of lung adenocarcinoma cells to gefitinib in vivo, inhibited tumor proliferation and induced tumor cell death [3]. In an A549 xenograft tumor model using female athymic nude mice, MYLS22 (10mg/kg, ip, 18d) significantly enhanced the anticancer efficacy of BAY-876 [6]. In the MDA-MB-231 xenograft tumor model of female mice, MYLS22 (10mg/kg, ip, 18d) inhibited the growth of TNBC in mice by inhibiting tumor growth, invasiveness and neovascularization [7]. MYLS22 (0, 12.5, 25 and 50mg/kg) inhibited L-OPA1, resulting in more severe lung tissue damage in mice and upregulated the inflammatory cytokines total IL-1β, IL-1β p17 and NF-κB p65 in vivo. Among them, 12.5mg/kg MYLS22 was sufficient to cause severe lung damage and inflammation in mice [8].
References:
[1]. Murata D, Ito F, Tang G, et al. mCAUSE: Prioritizing mitochondrial targets that alleviate pancreatic cancer cell phenotypes[J]. iScience. 2024 Sep 3; 27(9): 110880.
[2]. Herkenne S, Ek O, Zamberlan M, Pellattiero A, et al. Developmental and Tumor Angiogenesis Requires the Mitochondria-Shaping Protein Opa1[J]. Cell Metabolism. 2020 May 5; 31(5): 987-1003.
[3]. Noguchi M, Kohno S, Pellattiero A, et al. Inhibition of the mitochondria-shaping protein Opa1 restores sensitivity to Gefitinib in a lung adenocarcinomaresistant cell line[J]. Cell Death Disease. 2023 Apr 5; 14(4): 241.
[4]. Baek ML, Lee J, Pendleton KE, et al. Mitochondrial structure and function adaptation in residual triple negative breast cancer cells surviving chemotherapy treatment[J]. Oncogene. 2023 Mar; 42(14): 1117-1131.
[5]. Wang Y, Wang Y, Liu W, et al. TIM-4 orchestrates mitochondrial homeostasis to promote lung cancer progression via ANXA2/PI3K/AKT/OPA1 axis[J]. Cell Death Disease. 2023 Feb 20; 14(2): 141.
[6]. Guo Y, Luo C, Sun Y, et al. Inhibition of mitochondrial fusion via SIRT1/PDK2/PARL axis breaks mitochondrial metabolic plasticity and sensitizes cancer cells to glucose restriction therapy[J]. Biomedicine Pharmacotherapy. 2023 Oct; 166: 115342.
[7]. Zamberlan M, Boeckx A, Muller F, et al. Inhibition of the mitochondrial protein Opa1 curtails breast cancer growth[J]. Journal of Experimental & Clinical Cancer Research. 2022 Mar 12; 41(1): 95
[8]. Jiang HL, Yang HH, Liu YB, et al. L-OPA1 deficiency aggravates necroptosis of alveolar epithelial cells through impairing mitochondrial function during acute lung injury in mice[J]. Journal of Cellular Physiology. 2022 Jul; 237(7): 3030-3043.
MYLS22是视神经萎缩1(OPA1)的选择性抑制剂。MYLS22通过靶向内皮OPA1来抑制肿瘤生长,并通过影响NF-kB活性和血管生成基因表达来抑制血管生成。它具有抗血管生成和抗癌活性 [1-7]。
MYLS22(50μM)在2天后抑制PANC-1细胞的生长,并在72小时后减少细胞迁移 [1]。MYLS22(30μM,72h)可恢复吉非替尼诱导的PC9M2细胞线粒体凋亡 [3]。MYLS22(50μM,48h)显着增加阿霉素诱导的细胞杀伤力,并降低阿霉素介导的线粒体伸长和OXPHOS [4]。MYLS22(50μM,24h)通过抑制OPA1逆转TIM-4诱导的OXPHOS增强并破坏线粒体融合,从而减弱肺癌进展 [5]。
在使用C57BL6/J小鼠的皮下B16F10小鼠黑色素瘤模型中,MYLS22(10mg/kg,ip,6d)有效抑制了黑色素瘤的增殖和生长 [2]。在使用KSN/Slc小鼠的皮下PC9M2异种移植模型中,MYLS22(25mg/kg,po,18d)逆转了肺腺癌细胞对吉非替尼的体内耐药性,抑制了肿瘤增殖并诱导了肿瘤细胞死亡 [3]。在雌性无胸腺裸鼠的A549异种移植瘤模型中,MYLS22(10mg/kg,ip,18d)显著增强了BAY-876的抗癌效果 [6]。在雌性小鼠的MDA-MB-231异种移植瘤模型中,MYLS22(10mg/kg,ip,18d)通过抑制肿瘤生长、侵袭性和新生血管形成抑制了TNBC小鼠的生长 [7]。MYLS22(0、12.5、25和50mg/kg)抑制了L-OPA1,导致小鼠肺组织损伤更严重,并上调了体内炎症细胞因子总IL-1β、IL-1β p17和NF-κB p65。其中,12.5mg/kg MYLS22足以引起小鼠严重的肺损伤和炎症 [8]。
Cell experiment [1]: | |
Cell lines | PANC-1 cells |
Preparation Method | PANC-1 cells were then replated at 10,000 cells/well in a 96-well plate and cultured for 24h before being treated with 50μM MYLS22 for 2days. |
Reaction Conditions | 50μM; 2d |
Applications | MYLS22 exerts an inhibitory effect on pancreatic cancer cell migration by reducing 3D spheroid growth and wound healing migration, and inhibiting spheroid invasion and cell migration in PANC-1 cells. |
Animal experiment [2]: | |
Animal models | Subcutaneous B16F10 melanoma model |
Preparation Method | In a subcutaneous B16F10 melanoma model, MYLS22 treatment (10mg/kg every two days starting from day 10 post-injection) significantly affected tumor progression, as evaluated by daily tumor volume measurements using length×width²×0.5, with tumors harvested on day 16 for analysis. |
Dosage form | 10mg/kg; ip; 6d |
Applications | MYLS22 significantly inhibited melanoma growth in vivo in an endothelial Opa1-dependent manner. |
References: |
Cas No. | 306959-01-3 | SDF | |
别名 | N-(1,5-二甲基-3-氧代-2-苯基-2,3-二氢-1H-吡唑-4-基)-3-甲基-1-苯基-1H-噻吩并[2,3-C]吡唑-5-甲酰胺 | ||
Canonical SMILES | O=C(C(S1)=CC2=C1N(C3=CC=CC=C3)N=C2C)NC4=C(C)N(C)N(C5=CC=CC=C5)C4=O | ||
分子式 | C24H21N5O2S | 分子量 | 443.52 |
溶解度 | DMSO: 83.33 mg/mL (187.88 mM) | 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。 |
||
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 | |||
![]() |
1 mg | 5 mg | 10 mg |
1 mM | 2.2547 mL | 11.2734 mL | 22.5469 mL |
5 mM | 0.4509 mL | 2.2547 mL | 4.5094 mL |
10 mM | 0.2255 mL | 1.1273 mL | 2.2547 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet