Lorlatinib (PF-6463922)

For research use only.

Catalog No.S7536

20 publications

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. PF-06463922 induces apoptosis. Phase 1.

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Selleck's Lorlatinib (PF-6463922) has been cited by 20 publications

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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. 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)
<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 NF:0PHRHfW6ldHnvckBie3OjeR?= NHLxSIcyKGh? MoDzTY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzDGNVE4PExibYX0ZY51KGW6cILld5Nm\CCrbjDtc5V{\SCQSVitN3Q{KGOnbHzzJIF{e2W|c3XkJIF{KHCqb4PwbI8uSUyNIHzleoVtKGGodHXyJFEhcHJiYomgd4Fv\HerY3igSWxKW0F? Mn3zNlQ5OTlzMU[=

... 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)
Water Insoluble
Ethanol ''30 mg/mL warmed
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
Smiles CC1C2=C(C=CC(=C2)F)C(=O)N(CC3=NN(C(=C3C4=CC(=C(N=C4)N)O1)C#N)C)C

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Step 2: Enter the in vivo formulation ()
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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03726333 Recruiting Drug: lorlatinib Advanced Cancers Pfizer January 14 2020 Phase 1
NCT03505554 Recruiting Drug: Lorlatinib Anaplastic Large Cell Lymphoma ALK-Positive University of Milano Bicocca|Pfizer October 10 2017 Phase 2
NCT03107988 Recruiting Drug: Lorlatinib|Drug: Cyclophosphamide|Drug: Topotecan Neuroblastoma New Approaches to Neuroblastoma Therapy Consortium|Pfizer|University of Southern California|Solving Kids'' Cancer US/EU|Children''s Neuroblastoma Cancer Foundation|The Band of Parents|The Evan Foundation|Wade''s Army|Ronan Thompson Foundation|The Catherine Elizabeth Blair Memorial Foundation|Cookies for Kids'' Cancer September 1 2017 Phase 1
NCT03184168 Completed Drug: [14C]lorlatinib Healthy Volunteers Pfizer July 5 2017 Phase 1
NCT03439215 Recruiting Drug: Lorlatinib Carcinoma Non-Small-Cell Lung Fondazione Ricerca Traslazionale|Clinical Research Technology S.r.l. June 13 2017 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

Tel: +1-832-582-8158 Ext:3

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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.

ALK Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID