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MYLS22

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Chemical Structure| 306959-01-3 同义名 : -
CAS号 : 306959-01-3
货号 : A1097751
分子式 : C24H21N5O2S
纯度 : 95%
分子量 : 443.521
MDL号 : MFCD01062681
存储条件：

粉末 Keep in dark place,Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(56.37 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 The inner mitochondrial membrane mitochondrial fusion protein optic atrophy 1 (OPA1) is required for angiogenesis. In response to angiogenic stimuli, OPA1 levels rapidly increase to limit nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB) signaling, ultimately allowing angiogenic genes expression and angiogenesis. Endothelial Opa1 is indeed required in an NFκB-dependent pathway essential for developmental and tumor angiogenesis, impacting tumor growth and metastatization. MYLS22 is a first-in-class and selective OPA1 inhibitor. MYLS22 can target endothelial OPA1 to curtail tumor growth and inhibits angiogenesis by impinging on NFkB activity and on angiogenic gene expression. MYLS22 (10 mg/kg/die; peritumoral injection; every 2 days for 14 days) causes the tumor growth curtailed mice[2]. The offspring from crosses of a constitutive knockout for the structural complex I component Ndufs4 (Ndufs4(-/-)), and of a muscle-specific conditional knockout for the complex IV assembly factor Cox15 (Cox15(sm/sm)), with Opa1 transgenic (Opa1(tg)) mice showed improved motor skills and respiratory chain activities compared to the naive, non-Opa1-overexpressing, models. While the amelioration was modest in Ndufs4(-/-)::Opa1(tg) mice, correction of cristae ultrastructure and mitochondrial respiration, improvement of motor performance and prolongation of lifespan were remarkable in Cox15(sm/sm)::Opa1(tg) mice. Mechanistically, respiratory chain supercomplexes were increased in Cox15(sm/sm)::Opa1(tg) mice, and residual monomeric complex IV was stabilized[3]. Cardiac function and mitochondrial morphology were rescued by Oma1 deletion, which prevented OPA1 cleavage. Feeding mice a high-fat diet or ablating Yme1l in skeletal muscle restored cardiac metabolism and preserved heart function without suppressing mitochondrial fragmentation. Thus, unprocessed OPA1 is sufficient to maintain heart function, OMA1 is a critical regulator of cardiomyocyte survival, and mitochondrial morphology and cardiac metabolism are intimately linked[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.25mL

0.45mL

0.23mL

11.27mL

2.25mL

1.13mL

22.55mL

4.51mL

2.25mL
参考文献

[1]Herkenne S, Ek O, Zamberlan M, Pellattiero A, Chergova M, Chivite I, Novotná E, Rigoni G, Fonseca TB, Samardzic D, Agnellini A, Bean C, Di Benedetto G, Tiso N, Argenton F, Viola A, Soriano ME, Giacomello M, Ziviani E, Sales G, Claret M, Graupera M, Scorrano L. Developmental and Tumor Angiogenesis Requires the Mitochondria-Shaping Protein Opa1. Cell Metab. 2020 May 5;31(5):987-1003.e8. doi: 10.1016/j.cmet.2020.04.007. Epub 2020 Apr 20. PMID: 32315597.

[2] Stéphanie Herkenne, et al. Developmental and Tumor Angiogenesis Requires the Mitochondria-Shaping Protein Opa1. Cell Metab. 2020 May 5;31(5):987-1003.e8.

[3] Gabriele Civiletto,et al. Opa1 overexpression ameliorates the phenotype of two mitochondrial disease mouse models. Cell Metab. 2015 Jun 2;21(6):845-54.

[4]Timothy Wai,et al. Imbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice. Science. 2015 Dec 4;350(6265):aad0116.