马赛替尼

马赛替尼
临床数据
商品名（英语：Drug nomenclature）	Masivet, Kinavet
AHFS/Drugs.com	国际药品名称
ATC码	L01EX06 (WHO) ;
识别信息
	IUPAC命名法 4-[(4-Methylpiperazin-1-yl)methyl]-N-(4-methyl-3-{[4-(pyridin-3-yl)-1,3-thiazol-2-yl]amino}phenyl)benzamide; ;
CAS号	790299-79-5
PubChem CID	10074640;
ChemSpider	8250179;
UNII	M59NC4E26P;
KEGG	D10229;
ChEMBL	ChEMBL1908391;
PDB配体ID	G65 (PDBe, RCSB PDB);
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID001000207 ;
化学信息
化学式	C28H30N6OS
摩尔质量	498.65 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES O=C(c1ccc(cc1)CN2CCN(C)CC2)Nc3cc(c(cc3)C)Nc4nc(cs4)c5cccnc5;
	InChI InChI=InChI=1S/C28H30N6OSc1-20-5-10-24(16-25(20)31-28-32-26(19-36-28)23-4-3-11-29-17-23)30-27(35)22-8-6-21(7-9-22)18-34-14-12-33(2)13-15-34h3-11,16-17,19H,12-15,18H2,1-2H3,(H,30,35)(H,31,32); Key:WJEOLQLKVOPQFV-UHFFFAOYSA-N;

马赛替尼（商品名：Masivet）是一种酪氨酸激酶抑制剂，用于治疗动物肥大细胞瘤，尤其是狗。^[1]^[2]自2009年下半年以来，它已经在欧洲上市。^[3]马赛替尼已针对多种人类疾病进行了研究，包括黑色素瘤、多发性骨髓瘤、胃肠道癌、胰腺癌、阿尔茨海默病、多发性硬化症、类风湿性关节炎、肥大细胞增多症、肌萎缩性侧索硬化症和 COVID-19。^[4]^[5]^[6]

作用机制

马赛替尼是一种酪氨酸激酶抑制剂，可抑制酪氨酸激酶，这些酶负责通过信号转导级联激活许多蛋白质。具体来说，马赛替尼靶向受体酪氨酸激酶 c-Kit，该受体被发现在几种癌症中过度表达或发生突变。^[2]^[7]马赛替尼也是其他靶点，它还抑制血小板衍生生长因子受体（PDGFR）、淋巴细胞特异性蛋白酪氨酸激酶（Lck）、粘着斑激酶 (FAK) 和成纤维细胞生长因子受体3（FGFR3）以及集落刺激因子1受体（CSF1R）。^[8]^[9]

马赛替尼已被证明通过抑制其主要蛋白酶3CLpro来阻断SARS-CoV-2的复制。马赛替尼显示感染SARS-CoV-2的小鼠肺部和鼻子中的病毒滴度降低了200倍以上。^[4]

临床使用

马赛替尼正在研究用于治疗系统性肥大细胞增多症 (Masipro)，但由于担心“研究结果的可靠性”和研究设计的重大变化，2017 年欧盟拒绝批准。^[2]^[10]

2018 年，欧盟拒绝批准马赛替尼治疗肌萎缩性脊髓侧索硬化症 (Alsitek) 。^[10]

参考文献

^ Hahn, K.A.; Oglivie, G.; Rusk, T.; Devauchelle, P.; Leblanc, A.; Legendre, A.; Powers, B.; Leventhal, P.S.; Kinet, J.-P.; Palmerini, F.; Dubreuil, P. Masitinib is Safe and Effective for the Treatment of Canine Mast Cell Tumors. Journal of Veterinary Internal Medicine. 2008-11, 22 (6) [2022-06-19]. doi:10.1111/j.1939-1676.2008.0190.x. （原始内容存档于2022-06-19）（英语）.
^ ^2.0 ^2.1 ^2.2 Masivet. European Medicines Agency. [2022-06-19]. （原始内容存档于2022-06-18）.
^ Masitinib. PubChem. [2022-06-19]. （原始内容存档于2022-06-19）（英语）.
^ ^4.0 ^4.1 Drayman, Nir; DeMarco, Jennifer K.; Jones, Krysten A.; Azizi, Saara-Anne; Froggatt, Heather M.; Tan, Kemin; Maltseva, Natalia Ivanovna; Chen, Siquan; Nicolaescu, Vlad; Dvorkin, Steve; Furlong, Kevin. Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2. Science. 2021-08-20, 373 (6557) [2022-06-19]. ISSN 0036-8075. PMC 8809056  . PMID 34285133. doi:10.1126/science.abg5827. （原始内容存档于2022-06-19）（英语）.
^ EU/3/16/1722: Orphan designation for the treatment of amyotrophic lateral sclerosis. European Medicines Agency. [2022-06-19]. （原始内容存档于2022-06-19）.
^ Folch, Jaume; Petrov, Dmitry; Ettcheto, Miren; Pedrós, Ignacio; Abad, Sonia; Beas-Zarate, Carlos; Lazarowski, Alberto; Marin, Miguel; Olloquequi, Jordi; Auladell, Carme; Camins, Antoni. Masitinib for the treatment of mild to moderate Alzheimer’s disease. Expert Review of Neurotherapeutics. 2015-06-03, 15 (6). ISSN 1473-7175. PMID 25961655. doi:10.1586/14737175.2015.1045419.
^ Dubreuil, Patrice; Letard, Sébastien; Ciufolini, Marco; Gros, Laurent; Humbert, Martine; Castéran, Nathalie; Borge, Laurence; Hajem, Bérengère; Lermet, Anne; Sippl, Wolfgang; Voisset, Edwige. Masitinib (AB1010), a Potent and Selective Tyrosine Kinase Inhibitor Targeting KIT. PLOS ONE. 2009-09-30, 4 (9) [2022-07-30]. ISSN 1932-6203. PMC 2746281  . PMID 19789626. doi:10.1371/journal.pone.0007258. （原始内容存档于2022-06-19）（英语）.
^ Gil da Costa, Rui M. C-kit as a prognostic and therapeutic marker in canine cutaneous mast cell tumours: From laboratory to clinic. The Veterinary Journal. 2015-07-01, 205 (1). ISSN 1090-0233. PMID 26021891. doi:10.1016/j.tvjl.2015.05.002 （英语）.
^ Trias, Emiliano; Ibarburu, Sofía; Barreto-Núñez, Romina; Babdor, Joël; Maciel, Thiago T.; Guillo, Matthias; Gros, Laurent; Dubreuil, Patrice; Díaz-Amarilla, Pablo; Cassina, Patricia; Martínez-Palma, Laura. Post-paralysis tyrosine kinase inhibition with masitinib abrogates neuroinflammation and slows disease progression in inherited amyotrophic lateral sclerosis. Journal of Neuroinflammation. 2016-07-11, 13 (1). ISSN 1742-2094. PMC 4940876  . PMID 27400786. doi:10.1186/s12974-016-0620-9.
^ ^10.0 ^10.1 Public Health - European Commission. Union Register of medicinal products. [2022-06-19]. （原始内容存档于2018-06-11）（英语）.

[1] Hahn, K.A.; Oglivie, G.; Rusk, T.; Devauchelle, P.; Leblanc, A.; Legendre, A.; Powers, B.; Leventhal, P.S.; Kinet, J.-P.; Palmerini, F.; Dubreuil, P. Masitinib is Safe and Effective for the Treatment of Canine Mast Cell Tumors. Journal of Veterinary Internal Medicine. 2008-11, 22 (6) [2022-06-19]. doi:10.1111/j.1939-1676.2008.0190.x. （原始内容存档于2022-06-19）（英语）.

[ema-2] 2.0 ^2.1 ^2.2 Masivet. European Medicines Agency. [2022-06-19]. （原始内容存档于2022-06-18）.

[3] Masitinib. PubChem. [2022-06-19]. （原始内容存档于2022-06-19）（英语）.

[science-4] 4.0 ^4.1 Drayman, Nir; DeMarco, Jennifer K.; Jones, Krysten A.; Azizi, Saara-Anne; Froggatt, Heather M.; Tan, Kemin; Maltseva, Natalia Ivanovna; Chen, Siquan; Nicolaescu, Vlad; Dvorkin, Steve; Furlong, Kevin. Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2. Science. 2021-08-20, 373 (6557) [2022-06-19]. ISSN 0036-8075. PMC 8809056  . PMID 34285133. doi:10.1126/science.abg5827. （原始内容存档于2022-06-19）（英语）.

[5] EU/3/16/1722: Orphan designation for the treatment of amyotrophic lateral sclerosis. European Medicines Agency. [2022-06-19]. （原始内容存档于2022-06-19）.

[6] Folch, Jaume; Petrov, Dmitry; Ettcheto, Miren; Pedrós, Ignacio; Abad, Sonia; Beas-Zarate, Carlos; Lazarowski, Alberto; Marin, Miguel; Olloquequi, Jordi; Auladell, Carme; Camins, Antoni. Masitinib for the treatment of mild to moderate Alzheimer’s disease. Expert Review of Neurotherapeutics. 2015-06-03, 15 (6). ISSN 1473-7175. PMID 25961655. doi:10.1586/14737175.2015.1045419.

[7] Dubreuil, Patrice; Letard, Sébastien; Ciufolini, Marco; Gros, Laurent; Humbert, Martine; Castéran, Nathalie; Borge, Laurence; Hajem, Bérengère; Lermet, Anne; Sippl, Wolfgang; Voisset, Edwige. Masitinib (AB1010), a Potent and Selective Tyrosine Kinase Inhibitor Targeting KIT. PLOS ONE. 2009-09-30, 4 (9) [2022-07-30]. ISSN 1932-6203. PMC 2746281  . PMID 19789626. doi:10.1371/journal.pone.0007258. （原始内容存档于2022-06-19）（英语）.

[8] Gil da Costa, Rui M. C-kit as a prognostic and therapeutic marker in canine cutaneous mast cell tumours: From laboratory to clinic. The Veterinary Journal. 2015-07-01, 205 (1). ISSN 1090-0233. PMID 26021891. doi:10.1016/j.tvjl.2015.05.002 （英语）.

[9] Trias, Emiliano; Ibarburu, Sofía; Barreto-Núñez, Romina; Babdor, Joël; Maciel, Thiago T.; Guillo, Matthias; Gros, Laurent; Dubreuil, Patrice; Díaz-Amarilla, Pablo; Cassina, Patricia; Martínez-Palma, Laura. Post-paralysis tyrosine kinase inhibition with masitinib abrogates neuroinflammation and slows disease progression in inherited amyotrophic lateral sclerosis. Journal of Neuroinflammation. 2016-07-11, 13 (1). ISSN 1742-2094. PMC 4940876  . PMID 27400786. doi:10.1186/s12974-016-0620-9.

[europa-10] 10.0 ^10.1 Public Health - European Commission. Union Register of medicinal products. [2022-06-19]. （原始内容存档于2018-06-11）（英语）.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]