Lorlatinib (PF-6463922)

Catalog No.S7536 Batch:S753608

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Technical Data

Formula

C21H19FN6O2
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
In vivo (Add solvents to the product individually and in order)
Clear solution
5% DMSO 95% Corn oil
0.4mg/ml Taking the 1 mL working solution as an example, add 50 μL of 8 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
4.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 80 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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.)

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.
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)		 View More
<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]
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)

Customer Product Validation

Data from [Data independently produced by , , Oncotarget, 2016, DOI: 10.18632/oncotarget.13541.]

Data from [Data independently produced by , , Mol Cancer Res, 2018, 10.1158/1541-7786.MCR-18-0171]

Data from [Data independently produced by , , Int J Oncol, 2017, 51(5):1533-1540]

Selleck's Lorlatinib (PF-6463922) has been cited by 73 publications

NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations [ Cancer Discov, 2024, OF1-OF20.] PubMed: 39269178
LTK mutations responsible for resistance to lorlatinib in non-small cell lung cancer harboring CLIP1-LTK fusion [ Commun Biol, 2024, 7(1):412] PubMed: 38575808
HER3 overexpression: a predictive marker for poor prognosis in advanced ALK-positive non-small cell lung cancer treated with ALK inhibitors [ Transl Lung Cancer Res, 2024, 13(2):321-333] PubMed: 38496685
Synergistic Effects of Neratinib in Combination With Palbociclib or Miransertib in Brain Cancer Cells [ World J Oncol, 2024, 15(3):492-505] PubMed: 38751701
The Combination of Afatinib With Dasatinib or Miransertib Results in Synergistic Growth Inhibition of Stomach Cancer Cells [ World J Oncol, 2024, 15(2):192-208] PubMed: 38545471
Therapy-induced APOBEC3A drives evolution of persistent cancer cells [ Nature, 2023, 620(7973):393-401] PubMed: 37407818
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

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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.