Loratinib

Details:

CAS number :1454846-35-5

English name :Lorlatinib

English alias :Loratinib; PF0643922; PF-06463922; PF-6463922; 140539; CS-1727; EOS-60936; Lorbrena.; PF6463922; Laratinib

Molecular formula :C21H19FN6O2

Molecular weight :406.41

Melting point :184-187°C

Boiling point :675.0±55.0°C(Predicted)

Density :1.42±0.1g/cm3(Predicted)

Storage conditions: Hygroscopic, 20 ° CFreezer, Underinertatmosphere

Degree of Chemicalbook dissolution :Chloroform(Slightly),EthylAcetate(Slightly)

Form :Solid

Acidity coefficient (pKa):6.05±0.40(Predicted)

Color :WhitetoOff-White

Stability :Hygroscopic

Loratinib (PF-06463922) is an ALK inhibitor modified by Pfizer in the United States through Crizotinib, which entered clinical trials in 2014 for the treatment of lung cancer. It is mainly targeted at patients with non-small cell lung cancer who are resistant to first-generation ALK inhibitors crizotinib and second-generation ALK inhibitors ceritinib and Alectinib.

On April 27, 2017, Pfizer announced that its next-generation ALK/ROS1 inhibitor Lauratinib has been granted breakthrough drug designation by the FDA for ALK-positive, metastatic NSCLC whose disease has progressed after treatment with one or more ALK inhibitors.

Pharmacological action
Lauratinib is an ALK inhibitor. ALK is a receptor tyrosine kinase, belonging to the insulin receptor superfamily, and has a high degree of homology with leukocyte tyrosine kinase. ALK was first identified in 1994 in the form of the NPM1-ALK fusion gene in anaplastic large-celllymphoma (ALCL). The ALK gene is located in human chromosome 2p23 and encodes a polypeptide of 1620 amino acids, which is modified after translation to produce a mature ALK protein of 200-220kDa. ALK consists of 1030 amino acids, including extracellular ligand binding domain, transmembrane domain and intracellular tyrosine kinase domain. ALK is highly conserved in all species and is expressed in the adult brain and is thought to play an important role in the development and function of the nervous system. ALK is also expressed in the small intestine, testicles, prostate, and colon, but it is not expressed in normal lymphoid tissue, lung, and other tissues. ALK to activation of multiple signaling pathways in cells, including phospholipase C gamma, JAK kinase, signal transduction and transcriptional activation factor (signaltransducerandactivatoroftranscription - 3, STAT3), phosphatidyl inositol 3 kinase (PI3K phosphatidylinositol3 - kinase), mammals rapamycin target protein (mammaliantargetofrapamycin, mTOR) and silk crack amp-activated protein kinase (MAPK), etc.. It is involved in regulating cell growth, transformation and anti-apoptosis.