拉羅替尼

拉羅替尼
臨床資料
商品名	Vitrakvi
其他名稱	LOXO-101, ARRY-470
AHFS/Drugs.com	Monograph
MedlinePlus	a619006
核准狀況	美 DailyMed: Larotrectinib;
懷孕分級	澳: D ; ;
给药途径	By mouth, oropharyngeal
ATC碼	L01EX12 (WHO) ;
法律規範狀態
法律規範	澳：限医生处方（S4）; 加：处方药（℞-only）; 歐：Rx-only; 英：处方药（℞-only） (POM); 美：处方药（℞-only）;
识别信息
	IUPAC命名法 (3S)-N5-[(2R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl3-hydroxypyrrolidine-1-carboxamide; ;
CAS号	1223403-58-4
PubChem CID	46188928;
DrugBank	DB14723;
ChemSpider	44210503;
UNII	PF9462I9HX;
KEGG	D11137; as salt: D11138;
ChEMBL	ChEMBL3889654;
CompTox Dashboard (EPA)	DTXSID101020707 ;
化学信息
化学式	C21H22F2N6O2
摩尔质量	428.44 g·mol−1
3D模型（JSmol）	交互式图像;
	SMILES O=C(Nc1cnn2ccc(N3CCC[C@@H]3c3cc(F)ccc3F)nc12)N1CC[C@H](O)C1;
	InChI InChI=1S/C21H22F2N6O2/c22-13-3-4-16(23)15(10-13)18-2-1-7-28(18)19-6-9-29-20(26-19)17(11-24-29)25-21(31)27-8-5-14(30)12-27/h3-4,6,9-11,14,18,30H,1-2,5,7-8,12H2,(H,25,31)/t14-,18+/m0/s1; Key:NYNZQNWKBKUAII-KBXCAEBGSA-N;

拉羅替尼（INN：英語：Larotrectinib）是一種治療癌症的藥物^[1]^[5]^[7]。它是一種原肌球蛋白激酶（英语：tropomyosin kinase）受體（英语：Trk receptor）（TRK）的抑制劑，作用於TrkA（英语：TrkA）、TrkB（英语：TrkB）與TrkC（英语：TrkC）受體^[8]^[9]^[10]。該藥物由陣列生物製藥（英语：Array BioPharma）發現，並於2013年授權予洛克索腫瘤公司（Loxo Oncology）。

拉羅替尼最初於2015年取得軟組織肉瘤的孤兒藥資格，並於2016年取得針對帶有 NTRK 融合基因的轉移性實體腫瘤之突破性療法（英语：breakthrough therapy）資格^[11]。部分臨床試驗結果於2017年公布^[12]。2018年11月26日，取得美國食品藥物管理局的醫療許可^[13]。

拉羅替尼是首批專門針對「攜帶特定基因突變」的任何癌症而開發的藥物，而非依腫瘤原發的特定組織進行治療（即非組織特異性藥物（英语：tissue-agnostic drug））。許多較早期藥物，像帕博利珠單抗後來亦獲准用於不論來源組織但具特定突變基因的癌症，它最初開發時仍以特定癌種為目標。美国食品药品监督管理局將它列為首創藥物（英语：first-in-class medication）^[14]。

拉羅替尼於2019年9月獲得歐盟核准用於醫療用途^[15]^[6]。並於2020年8月在澳洲核准使用^[1]。

參考文獻

^ ^1.0 ^1.1 ^1.2 Vitrakvi. Therapeutic Goods Administration（英语：Therapeutic Goods Administration） (TGA). 16 September 2020 [22 September 2020]. （原始内容存档于19 September 2020）.
^ Vitrakvi Product information. Health Canada. 25 April 2012 [29 May 2022]. （原始内容存档于30 May 2022）.
^ Summary Basis of Decision (SBD) for Vitrakvi. Health Canada. 23 October 2014 [29 May 2022]. （原始内容存档于31 May 2022）.
^ Vitrakvi 25mg hard capsules - Summary of Product Characteristics (SmPC). (emc). 7 March 2022 [28 November 2022]. （原始内容存档于28 November 2022）.
^ ^5.0 ^5.1 Vitrakvi- larotrectinib capsule Vitrakvi- larotrectinib solution, concentrate. DailyMed. 26 July 2019 [22 September 2020]. （原始内容存档于7 April 2021）.
^ ^6.0 ^6.1 Vitrakvi EPAR. European Medicines Agency (EMA). 23 July 2019 [22 September 2020]. （原始内容存档于2 October 2020）.
^ Larotrectinib (PDF). Statement on a Nonproprietary Name Adopted by the USAN Council. American Medical Association (AMA). 26 October 2016 [31 January 2017]. （原始内容存档 (PDF)于13 March 2018）.
^ Berger S, Martens UM, Bochum S. Larotrectinib (LOXO-101). Small Molecules in Oncology. Recent Results in Cancer Research Fortschritte der Krebsforschung. Progres dans les Recherches Sur le Cancer 211. 2018: 141–151. ISBN 978-3-319-91441-1. PMID 30069765. doi:10.1007/978-3-319-91442-8_10.
^ Federman N, McDermott R. Larotrectinib, a highly selective tropomyosin receptor kinase (TRK) inhibitor for the treatment of TRK fusion cancer. Expert Review of Clinical Pharmacology. October 2019, 12 (10): 931–939. PMID 31469968. doi:10.1080/17512433.2019.1661775 .
^ Scott LJ. Larotrectinib: First Global Approval. Drugs. February 2019, 79 (2): 201–206. PMID 30635837. S2CID 57772716. doi:10.1007/s40265-018-1044-x.
^ Larotrectinib. AdisInsight. [31 January 2017]. （原始内容存档于12 March 2018）.
^ Novel Agent Shows Antitumor Activity in TRK-Fusion Cancers. June 2017. [9 June 2017]. （原始内容存档于24 January 2021）.
^ FDA approves larotrectinib for solid tumors with NTRK gene fusions. U.S. Food and Drug Administration (FDA). 26 November 2018 [22 September 2020]. （原始内容存档于24 March 2021）.
^ New Drug Therapy Approvals 2018. U.S. Food and Drug Administration (FDA) (报告). January 2019 [16 September 2020]. （原始内容 (PDF)存档于17 September 2020）.
^ Gallagher J. 'Revolutionary' new class of cancer drugs approved. 23 September 2019 [30 September 2019]. （原始内容存档于26 September 2019）（英国英语）.

外部連結

Larotrectinib sulfate. National Cancer Institute. 6 December 2018.
Larotrectinib sulfate. NCI Dictionary of Cancer Terms. National Cancer Institute.

[Vitrakvi_AU_summary-1] 1.0 ^1.1 ^1.2 Vitrakvi. Therapeutic Goods Administration（英语：Therapeutic Goods Administration） (TGA). 16 September 2020 [22 September 2020]. （原始内容存档于19 September 2020）.

[2] Vitrakvi Product information. Health Canada. 25 April 2012 [29 May 2022]. （原始内容存档于30 May 2022）.

[3] Summary Basis of Decision (SBD) for Vitrakvi. Health Canada. 23 October 2014 [29 May 2022]. （原始内容存档于31 May 2022）.

[4] Vitrakvi 25mg hard capsules - Summary of Product Characteristics (SmPC). (emc). 7 March 2022 [28 November 2022]. （原始内容存档于28 November 2022）.

[Vitrakvi_FDA_label-5] 5.0 ^5.1 Vitrakvi- larotrectinib capsule Vitrakvi- larotrectinib solution, concentrate. DailyMed. 26 July 2019 [22 September 2020]. （原始内容存档于7 April 2021）.

[Vitrakvi_EPAR-6] 6.0 ^6.1 Vitrakvi EPAR. European Medicines Agency (EMA). 23 July 2019 [22 September 2020]. （原始内容存档于2 October 2020）.

[7] Larotrectinib (PDF). Statement on a Nonproprietary Name Adopted by the USAN Council. American Medical Association (AMA). 26 October 2016 [31 January 2017]. （原始内容存档 (PDF)于13 March 2018）.

[pmid30069765-8] Berger S, Martens UM, Bochum S. Larotrectinib (LOXO-101). Small Molecules in Oncology. Recent Results in Cancer Research Fortschritte der Krebsforschung. Progres dans les Recherches Sur le Cancer 211. 2018: 141–151. ISBN 978-3-319-91441-1. PMID 30069765. doi:10.1007/978-3-319-91442-8_10.

[pmid31469968-9] Federman N, McDermott R. Larotrectinib, a highly selective tropomyosin receptor kinase (TRK) inhibitor for the treatment of TRK fusion cancer. Expert Review of Clinical Pharmacology. October 2019, 12 (10): 931–939. PMID 31469968. doi:10.1080/17512433.2019.1661775 .

[pmid30635837-10] Scott LJ. Larotrectinib: First Global Approval. Drugs. February 2019, 79 (2): 201–206. PMID 30635837. S2CID 57772716. doi:10.1007/s40265-018-1044-x.

[adis-11] Larotrectinib. AdisInsight. [31 January 2017]. （原始内容存档于12 March 2018）.

[12] Novel Agent Shows Antitumor Activity in TRK-Fusion Cancers. June 2017. [9 June 2017]. （原始内容存档于24 January 2021）.

[13] FDA approves larotrectinib for solid tumors with NTRK gene fusions. U.S. Food and Drug Administration (FDA). 26 November 2018 [22 September 2020]. （原始内容存档于24 March 2021）.

[14] New Drug Therapy Approvals 2018. U.S. Food and Drug Administration (FDA) (报告). January 2019 [16 September 2020]. （原始内容 (PDF)存档于17 September 2020）.

[15] Gallagher J. 'Revolutionary' new class of cancer drugs approved. 23 September 2019 [30 September 2019]. （原始内容存档于26 September 2019）（英国英语）.

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