PF-06463922, Lorlatinib
Lorlatinib
CAS: 1454846-35-5
Molecular Formula: C21H19FN6O2
PF-06463922, Lorlatinib - Names and Identifiers
PF-06463922, Lorlatinib - Physico-chemical Properties
| Molecular Formula | C21H19FN6O2 |
| Molar Mass | 406.41 |
| Density | 1.42±0.1 g/cm3(Predicted) |
| Melting Point | 184-187°C |
| Boling Point | 675.0±55.0 °C(Predicted) |
| Water Solubility | Chloroform (Slightly), Ethyl Acetate (Slightly) |
| Solubility | DMSO: ≥ 28 mg/mL |
| Appearance | Solid White to Off-White |
| Color | White to Off-White |
| pKa | 6.05±0.40(Predicted) |
| Storage Condition | Hygroscopic, -20°C Freezer, Under inert atmosphere |
| Stability | Hygroscopic |
| Use | Lorantinib (PF-06463922) is an ALK inhibitor modified by Pfizer (Pfizer) through crizotinib (Crizotinib). The drug entered clinical trials in 2014 for the treatment of lung cancer, mainly for the first generation of non-small cell lung cancer patients who are resistant to the ALK inhibitor crizotinib and the second generation of ALK inhibitors seritinib (Ceritinib) and erentinib (Alectinib). |
| In vitro study | PF-06463922 showed significant cellular activity against ALK and a large number of ALK clinical mutants with an IC50 range of 0.2 nM-77 nM. In HCC78 human NSCLC cells containing SLC34A2-ROS1 fusion and CD74-ROS1 cells expressing human BaF3-CD74-ROS1, PF-06463922 significantly inhibited cell proliferation and induced apoptosis. In NSCLC cells containing non-mutant ALK or mutant ALK fusions, PF-06463922 also exhibited potent growth inhibitory activity and induced apoptosis. |
| In vivo study | In rats, PF-06463922 showed low plasma clearance, modest volume of distribution, reasonable half-life, low sensitivity to low P-glycoprotein 1 mediated efflux, and a bioavailability of 100%. In vivo, CD74-ROS1 of NIH3T3 xenograft models expressing human Fig-ROS1 and PF-06463922 showed a cell-reducing anticancer effect by inhibiting ROS1 phosphorylation and downstream signaling molecules, and play a role in the inhibition of cyclin D1 in tumors. EML4-ALK also showed significant anti-tumor activity in mice overexpressing EML4-ALK-L1196M,EML4-ALK-G1269A,EML4-ALK-G1202R, NPM-ALK or PF-06463922 of the tumor grafts. |
PF-06463922, Lorlatinib - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.461 ml | 12.303 ml | 24.606 ml |
| 5 mM | 0.492 ml | 2.461 ml | 4.921 ml |
| 10 mM | 0.246 ml | 1.23 ml | 2.461 ml |
| 5 mM | 0.049 ml | 0.246 ml | 0.492 ml |
Last Update：2024-01-02 23:10:35
PF-06463922, Lorlatinib - Introduction
Indications
On April 27, 2017, Pfizer announced that its new generation of ALK/ROS1 inhibitor lorotinib was granted breakthrough drug status by FDA for advanced, ALK-positive and metastatic NSCLC that has received one or more ALK inhibitors in the past.
Pharmacological effects
Lorantinib is an ALK inhibitor. ALK is a receptor tyrosine kinase, which belongs to the insulin receptor superfamily and has high homology with leukocyte tyrosine kinase. In 1994, ALK was first discovered in anaplastic large cell lymphoma (large-celllymphoma,ALCL) in the form of NPM1-ALK fusion gene. ALK gene is located on human chromosome 2 p23 and encodes a polypeptide of 1620 amino acids. After post-translational modification, it generates mature ALK protein of 200~220 kDa. ALK consists of 1030 amino acids consisting of extracellular ligand binding domain, transmembrane domain and intracellular tyrosine kinase domain. ALK is highly conserved in all species. ALK expressed in adult brain is considered to play an important role in the development and function of nervous system. ALK is also expressed in small intestine, testis, prostate and colon, but it is not expressed in normal lymphoid tissues, lung and other tissues. ALK can activate multiple intracellular signaling pathways, including phospholipase C & gamma;,JAK kinase, signal transducer and transcription activator (signaltransducer and activator of transcription-3,STAT3), phosphatidylinositol -3-kinase (phosphatidylinositol 3-kinase,PI3K), mammalian target of rapamycin (mammaliantarget of rapamycin,mTOR) and mitogen-activated protein kinase (MAPK), etc, involved in regulating cell growth, transformation and anti-apoptosis.
Use
Lorantinib should be regarded as the third-generation ALK inhibitor, which can inhibit 9 mutations of crizotinib resistance, has strong blood-brain barrier penetration ability, and has strong brain entry effect. It is especially suitable for advanced NSCLC patients with other ALK resistance. Lorantinib carries EGFR-sensitive mutations in advanced non-small cell lung cancer, which can be treated with many EGFR inhibitors, such as the first-generation drug Iressa, Tarceva, Camelina, and the second-generation drug Afatinib, dactinib, the third-generation drug osimertinib (AZD9291)-these targeted drugs have an effective rate of 70% or even higher, and have few side effects. They are the first choice for treatment of such patients.
Last Update：2024-04-09 19:55:45
Supplier List
Spot supply
Product Name: Lorlatinib Visit Supplier Webpage Request for quotationCAS: 1454846-35-5
Tel: 0714-3999186
Email: 2853786052@qq.com
Mobile: 86+15671228036
QQ: 2853786052
Wechat: 15671228036
Spot supply
Product Name: PF-06463922 Visit Supplier Webpage Request for quotationCAS: 1454846-35-5
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
Spot supply
Product Name: Lorlatinib Visit Supplier Webpage Request for quotationCAS: 1454846-35-5
Tel: 0714-3999186
Email: 2853786052@qq.com
Mobile: 86+15671228036
QQ: 2853786052
Wechat: 15671228036
Spot supply
Product Name: PF-06463922 Visit Supplier Webpage Request for quotationCAS: 1454846-35-5
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
View History