Lorlatinib acetate_product_DataBase

Bioactivity	Lorlatinib (PF-06463922) acetate is a selective, orally active, brain-penetrant and ATP-competitive ROS1/ALK inhibitor with anticancer activity. Lorlatinib acetate has Kis of <0.025 nM, <0.07 nM, and 0.7 nM for ROS1, wild type ALK, and ALKL1196M, respectively. Lorlatinib acetate targets to EML4-ALK, and inhibits ALK phosphorylation with IC50s of 15-43 nM (ALKL1196), 14-80 nM (ALKG1269A), 38-50 nM (ALK1151Tins), 77-113 nM (ALKG1202R), respectively[1][2][3].
Invitro	Lorlatinib (PF-06463922) acetate 对 ALK 和大量 ALK 临床突变具有显著的细胞活性，IC50 范围为 0.2 nM-77 nM[1]。在携带 SLC34A2-ROS1 融合基因的 HCC78 人 NSCLC 细胞和表达人 CD74-ROS1 的 BaF3-CD74-ROS1 细胞中，Lorlatinib acetate显著抑制细胞增殖并诱导细胞凋亡。Lorlatinib acetate还显示出强大的生长抑制活性，并在携带非突变 ALK 或突变 ALK 融合的 NSCLC 细胞中诱导细胞凋亡[2]。 MCE has not independently confirmed the accuracy of these methods. They are for reference only. 0 --> Lorlatinib acetate 相关抗体:
In Vivo	在大鼠中，Lorlatinib (PF-06463922) 表现出低血浆清除率、中等分布容积、合理的半衰期、低 p-糖蛋白 1 介导的外排倾向和 100% 的生物利用度[1]。在体内，Lorlatinib 通过抑制 ROS1 磷酸化和下游信号分子，以及抑制肿瘤中的细胞周期蛋白 Cyclin D1，在表达人 CD74-ROS1 和 Fig-ROS1 的 NIH3T3 异种移植模型中显示细胞减灭性抗肿瘤功效。Lorlatinib 还在携带表达 EML4-ALK、EML4-ALK-L1196M、EML4-ALK-G1269A、EML4-ALK-G1202R 或 NPM-ALK[2]的肿瘤异种移植物的小鼠中表现出显著的抗肿瘤活性。 MCE has not independently confirmed the accuracy of these methods. They are for reference only.
CAS	1924207-18-0
Formula	C23H23FN6O4
Molar Mass	466.46
Transport	Room temperature in continental US; may vary elsewhere.
Storage	Please store the product under the recommended conditions in the Certificate of Analysis.
Reference	[1]. Zou HY, et al. PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models. Cancer Cell. 2015 Jul 13;28(1):70-81. [2]. Johnson TW, et al. Discovery of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations. J Med Chem. 2014 Jun 12;57(11):4720-44. [3]. Zou HY, et al. PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking PF-02341066-resistant ROS1 mutations. Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3493-8

PeptideDB

Lorlatinib acetate

CAS: 1924207-18-0 F: C23H23FN6O4 W: 466.46