辉瑞肺癌药物赛可瑞(克唑替尼, Crizotinib, Xalkori)

Pfizer’s lung cancer medicine crizotinib (brand name:Xalkori, previouly known as PF-02341066, Chinese brand name:赛可瑞, Chinese generic name:克唑替尼), an orally selective c_MET/ALK dual inhibitor, was granted accelerated approval on August 26, 2011 and regular approval on November 20, 2013 by the U.S. Food and Drug Administration (FDA) for the treatment of advanced non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by a FDA-approved test.

Structure of Pfizer's Lung Cancer Drug Crizotinib (Xalkori) 辉瑞肺癌药物克唑替尼(赛可瑞)的化学结构式

Xalkori, the first ALK inhibitor approved in ALK+ NSCLC patients, carries a $9,600 per month price tag, or $115,000 for patients who take it for a year.

Synthesis of Pfizer’s Lung Cancer Drug Crizotinib (Xalkori) 辉瑞肺癌药物克唑替尼(赛可瑞)的化学合成

Synthesis of Pfizer's Lung Cancer Drug Crizotinib (Xalkori) 辉瑞肺癌药物克唑替尼(赛可瑞)的化学合成

Trade Name: Xalkori
Generic Name: Crizotinib
Chinese Name: 赛可瑞 (brand name), 克唑替尼 (generic name)
Synonym: PF-02341066, Crizalk
Chemical Name:3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine
CAS number:877399-52-5
US patent number: US7230098, US7825137, US7858643 (download pdf file here), US8217057 (download pdf file here)
Patent Expiration Date:March 1, 2025(US7230098), May 12, 2027(US7825137), Oct 8, 2029(US7858643), Nov 6, 2029(US8217057)
Mechanism of Action:first-in-class inhibitor of a tumour- specific protein anaplastic lymphoma kinase (ALK)
Indication:ALK-positive Non-small cell lung cancer (NSCLC)
Date of Approval:August 26, 2011 (accelerated approval), November 20, 2013 (regular approval)
Developers: Pfizer

Sources:

Jingrong Jean Cui et al;Aminoheteroaryl compounds as protein kinase inhibitors;US patent number US7230098 B2;Also published as:CA2517256A1, CA2517256C, CN103265477A, EP1603570A2, EP1603570A4, EP1603570B1, EP1603570B9, EP2476667A2, EP2476667A3, US8106197, US20050009840, US20070072874, WO2004076412A2, WO2004076412A3;Filing date:Feb 26, 2004;Original Assignee:Pfizer Inc.

James Gail Christensen, Yahong Zou;Method of treating abnormal cell growth;US patent number US7825137 B2;Also published as:CA2632286A1, CA2632286C, DE602006018354D1, EP1959955A2, EP1959955B1, US20080300273, WO2007066187A2, WO2007066187A3;Filing date:Nov 23, 2006;Original Assignee:Pfizer Inc.

Jingrong Jean Cui et al;Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors;US patent number US7858643 B2 (download pdf file here),;Also published as:CA2578066A1, CA2578066C, CN101023064A, CN101023064B, DE602005020465D1, EP1786785A2, EP1786785B1, EP1786785B9, US20060046991, US20100324061, US20120263706, WO2006021884A2, WO2006021884A3;Filing date:Aug 26, 2005;Original Assignee:Agouron Pharmaceuticals, Inc.

Jingrong Jean Cui, Michelle Bich Tran-Dubé;Polymorphs of a c-MET/HGFR inhibitor;US patent number US8217057 B2 (download pdf file here);Also published as:CA2632283A1, CA2632283C, CN101326175A, CN101326175B, EP1963302A2, EP1963302B1, US20080293769, WO2007066185A2, WO2007066185A3;Filing date:Nov 23, 2006;Original Assignee:Pfizer Inc.

Christensen, James Gail and Zou, Yahong; Crizotinib for use in the treatment of cancer, PCT Int. Appl., WO2013017989

Lu, Guoliang et al; Synthetic method of crizotinib as molecular targeted antitumor drug;Faming Zhuanli Shenqing, 102532106; 04 Jul 2012

Tang, Hong; Method for preparing crizotinib; Faming Zhuanli Shenqing, 102584795, 18 Jul 2012

Cui, J. Jean et al; Structure Based Drug Design of Crizotinib (PF-02341066), a Potent and Selective Dual Inhibitor of Mesenchymal-Epithelial Transition Factor (c-MET) Kinase and Anaplastic Lymphoma Kinase (ALK); Journal of Medicinal Chemistry, 54(18), 6342-6363; 2011

De Koning, Pieter D. et al; Fit-for-Purpose Development of the Enabling Route to Crizotinib (PF-02341066); Organic Process Research & Development, 15(5), 1018-1026; 2011

Shen, Lixin et al; Method for preparing c-met inhibitor PF22341066; Faming Zhuanli Shenqing, 101735198, 16 Jun 2010

Goetsch, Liliane; Combination of a c-Met antagonist and an aminoheteroaryl compound for the treatment of cancer; PCT Int. Appl., WO2010003992, 14 Jan 2010

Christensen, James Gail and Zou, Yahong; N-Piperidinyl-4-(pyridin-5-yl)pyrazole compounds and their preparation and method of treating abnormal cell growth; PCT Int. Appl., WO2007066187, 14 Jun 2007

辉瑞（Pfizer）抗癌药物克唑替尼（Crizotinib）2013年11月21日获得了FDA的正式批准，商品名赛可瑞（Xalkori）用于经FDA批准的一款检测试剂盒证实其肿瘤为间变性淋巴瘤激酶（ALK）阳性的转移性非小细胞肺癌（NSCLC）患者的治疗。这是第一个对间变性淋巴瘤激酶 (ALK)进行靶向治疗的药物。

肺癌是癌症致死的主要原因之一，据估计，每年约有140万人死于肺癌。出于ALK阳性NSCLC患者对新药迫切需求的考虑，FDA于2011年8月授予了Xalkori加速批准（accelerated approval）。2013年2月，赛可瑞（克唑替尼,Crizotinib,CRIZALK, XALKORI）被国家食品药品监督管理局（SFDA）批准批准用于非小细胞肺癌治疗。这是第一个用于经SFDA批准的检测方法确定的间变性淋巴瘤激酶（ALK）阳性的局部晚期或转移性非小细胞肺癌（NSCLC）患者治疗的药物。