Lorlatinib (PF-6463922)

Catalog No.S7536

Lorlatinib (PF-6463922) Chemical Structure

Molecular Weight(MW): 406.41

PF-06463922 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. Phase 1.

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Cited by 7 Publications

3 Customer Reviews

  • Sub-G1 and cell cycle phase distribution of NBLW and NBLW-R cells treated for 24 hours with DMSO, 1× or 10× the respective GI 50 concentrations of PF-06463922.

    Oncotarget, 2016, DOI: 10.18632/oncotarget.13541.. Lorlatinib (PF-6463922) purchased from Selleck.

    NIH 3T3 cells expressing the indicated ALK variants were treated with increasing concentrations of lorlatinib (B) for 72 hours. Propidium iodide (PI) and Hoechst 33342 were added and allowed to incubate for 20 minutes before imaging on the ImageXpress. Dose-response curves were generated by determining total live cells (# of Hoechst-positive cells minus # of PI-positive cells) at each dose. A nonlinear regression of the data is represented here.

    Mol Cancer Res, 2018, 10.1158/1541-7786.MCR-18-0171. Lorlatinib (PF-6463922) purchased from Selleck.

  • H2228 cells were treated with the ALK-inhibitors, alectinib (500 nM), ceritinib (500 nM) and lorlatinib (100 nM) alone or with saracatinib (1 µM).

    Int J Oncol, 2017, 51(5):1533-1540. Lorlatinib (PF-6463922) purchased from Selleck.

Purity & Quality Control

Choose Selective ALK Inhibitors

Biological Activity

Description PF-06463922 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. Phase 1.
Targets
ROS1 [1]
(Cell-free assay)		 ALK [1]
(Cell-free assay)		 ALK (L1196M) [1]
(Cell-free assay)		 LTK (TYK1) [1]
(Cell-free assay)		 FER [1]
(Cell-free assay)
<0.02 nM(Ki) <0.07 nM(Ki) 0.07 nM(Ki) 2.7 nM 3.3 nM
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]
Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
mouse NIH-3T3 cells MYDGeY5kfGmxbjDhd5NigQ>? MVexJIg> NV71eYMzUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BHOTF5NFygcZV1[W62IHX4dJJme3OnZDDpckBud3W|ZTDOTWguO1R|IHPlcIx{KGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIHHmeIVzKDFiaIKgZpkhe2GwZIfpZ4ghTUyLU1G= M2[2fVI1QDF7MUG2

... Click to View More Cell Line Experimental Data
Assay
Methods Test Index PMID
Western blot
p-ALK / ALK; 

PubMed: 29650534     


ALK phosphorylation in the same Ba/F3 models treated with lorlatinib, as assessed by immunoblotting of cell lysates. Lorlatinib potently suppresses ALK activation in non-mutant and single mutant EML4-ALK models, but fails to inhibit ALK in Ba/F3 cells expressing the compound mutant.

29650534
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

Solubility (25°C)

In vitro DMSO 81 mg/mL warmed (199.3 mM)
Ethanol 30 mg/mL warmed (73.81 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
2% DMSO+30% PEG 300+ddH2O
For best results, use promptly after mixing. 		5mg/mL

* 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.

Chemical Information

Molecular Weight 406.41
Formula

C21H19FN6O2
CAS No. 1454846-35-5
Storage powder
in solvent
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02838264 Completed Healthy Pfizer August 16 2016 Phase 1
NCT02838264 Completed Healthy Pfizer August 16 2016 Phase 1
NCT02804399 Completed Healthy Pfizer July 2016 Phase 1
NCT02804399 Completed Healthy Pfizer July 2016 Phase 1
NCT02569554 Completed Healthy Pfizer December 2015 Phase 1
NCT02584634 Active not recruiting Non-Small Cell Lung Cancer Pfizer December 18 2015 Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

  • Question 1:

    Do you have any special suggestions for solution of S7536, Lorlatinib (PF-6463922) to be applied to mouse models?

  • Answer:

    For S7536, we recommend 2% DMSO+30% PEG 300+ddH2O (up to 5mg/ml) for in vivo application.

selleck catalog

ALK Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID