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Technical Data
| Formula | C21H19FN6O2 |
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| Molecular Weight | 406.41 | CAS No. | 1454846-35-5 | |
| Solubility (25°C)* | In vitro | DMSO | 81 mg/mL (199.3 mM) | |
| Ethanol | 81 mg/mL (199.3 mM) | |||
| Water | Insoluble | |||
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
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Preparing Stock Solutions
Biological Activity
| Description | Lorlatinib (PF-6463922) is a potent, dual ALK/ROS1 inhibitor with Ki of <0.02 nM, <0.07 nM, and 0.7 nM for ROS1, ALK (WT), and ALK (L1196M), respectively. PF-06463922 induces apoptosis. Phase 1. | |||||||||||
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| Targets |
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| In vitro | PF-06463922 demonstrates significant cell activity against ALK and a large set of ALK clinical mutations with IC50 ranging from 0.2 nM-77 nM. [1] PF-06463922 significantly inhibits cell proliferation and induces cell apoptosis in the HCC78 human NSCLC cells harboring SLC34A2-ROS1 fusions and the BaF3-CD74-ROS1 cells expressing human CD74-ROS1.[2] PF-06463922 also shows potent growth inhibitory activity and induces apoptosis in the NSCLC cells harboring either non-mutant ALK or mutant ALK fusions. [3] | |||||||||||
| In vivo | In rats, PF-06463922 displays low plasma clearance, a moderate volume of distribution, a reasonable half-life, low propensity for p-glycoprotein 1-mediated efflux and a bioavailability of 100%. [1] In vivo, PF-06463922 shows cytoreductive antitumor efficacy in the NIH3T3 xenograft models expressing human CD74-ROS1 and Fig-ROS1 via inhibition in ROS1 phosphorylation and the downstream signaling molecules, as well as inhibition of the cell cycle protein Cyclin D1 in tumors. [2] In vivo, PF-06463922 also demonstrates marked antitumor activity in mice bearing tumor xenografts expressing EML4-ALK, EML4-ALK-L1196M, EML4-ALK-G1269A, EML4-ALK-G1202R or NPM-ALK. [3] |
Protocol (from reference)
References
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Customer Product Validation
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Data from [Data independently produced by , , Oncotarget, 2016, DOI: 10.18632/oncotarget.13541.]
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Data from [Data independently produced by , , Mol Cancer Res, 2018, 10.1158/1541-7786.MCR-18-0171]
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Data from [Data independently produced by , , Int J Oncol, 2017, 51(5):1533-1540]
Selleck's Lorlatinib (PF-6463922) has been cited by 65 publications
| NVL-520 Is a Selective, TRK-Sparing, and Brain-Penetrant Inhibitor of ROS1 Fusions and Secondary Resistance Mutations [ Cancer Discov, 2023, 13(3):598-615] | PubMed: 36511802 |
| Circulating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma [ Nat Commun, 2023, 14(1):2601] | PubMed: 37147298 |
| Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models [ Clin Cancer Res, 2023, 29(7):1317-1331] | PubMed: 36602782 |
| Discovery of oncogenic ROS1 missense mutations with sensitivity to tyrosine kinase inhibitors [ EMBO Mol Med, 2023, 10.15252/emmm.202217367] | PubMed: 37587872 |
| Adaptive resistance to lorlatinib via EGFR signaling in ALK-rearranged lung cancer [ NPJ Precis Oncol, 2023, 7(1):12] | PubMed: 36702855 |
| FGFR blockade inhibits targeted therapy-tolerant persister in basal FGFR1- and FGF2-high cancers with driver oncogenes [ NPJ Precis Oncol, 2023, 7(1):107] | PubMed: 37880373 |
| FGFR blockade inhibits targeted therapy-tolerant persister in basal FGFR1- and FGF2-high cancers with driver oncogenes [ NPJ Precis Oncol, 2023, 7(1):107] | PubMed: 37880373 |
| Pan-HER inhibitors overcome lorlatinib resistance caused by NRG1/HER3 activation in ALK-rearranged lung cancer [ Cancer Sci, 2023, 10.1111/cas.15579] | PubMed: 36086904 |
| Pan-HER inhibitors overcome lorlatinib resistance caused by NRG1/HER3 activation in ALK-rearranged lung cancer [ Cancer Sci, 2023, 114(1):164-173] | PubMed: 36086904 |
| Tyrosine Kinase Inhibitors Target B Lymphocytes [ Biomolecules, 2023, 13(3)438] | PubMed: 36979373 |
RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.
SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.
NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.