Loratinib (PF-06463922; Lorlatinib; lorbrena)

Description: Loratinib (formerly also known as Lorlatinib, PF-06463922; trade name: Lorbrena) is a potent, orally bioavailable, brain-penetrant, ATP-competitive, and dual ALK/ROS1 inhibitor with potential antitumor activity. It inhibits ROS1, ALK (WT), and ALK (L1196M) with Ki values of< 0.02 nM, < 0.07 nM, and 0.7 nM, respectively. Loratinib was approved by FDA for treating patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer. Upon administration, PF-06463922 binds to and inhibits both ALK and ROS1 kinases which leads to disruption of ALK- and ROS1-mediated signaling and eventually inhibition of tumor cell growth. PF-06463922 has potential for treating ROS1 fusion-positive cancers, including those requiring agents with CNS-penetrating properties, as well as for overcoming crizotinib resistance driven by ROS1 mutation.

References: J Med Chem. 2014 Jun 12; 57(11):4720-44; Clin Cancer Res. 2012 Sep 1; 18(17):4570-9.

Related CAS: 2135926-03-1 (maleate); 1924207-18-0 (PF-06463922 acetate); 2306217-6 (hydrate) 1454846-35-5 (free base);

Chemical Name: (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.

InChi Key: IIXWYSCJSQVBQM-LLVKDONJSA-N

InChi Code: InChI=1S/C21H19FN6O2/c1-11-15-7-13(22)4-5-14(15)21(29)27(2)10-16-19(17(8-23)28(3)26-16)12-6-18(30-11)20(24)25-9-12/h4-7, 9, 11H, 10H2, 1-3H3, (H2, 24, 25)/t11-/m1/s1