Lorlatinib (PF-06463922) | ALK/ROS1 Inhibitor | CAS 1454846-35-5

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Quality Control

Batch: Purity: 99.95%

99.95

Related Targets	EGFR VEGFR PDGFR FGFR c-Met Src MEK CSF-1R FLT3 HER2
Other ALK Products	TAE684 (NVP-TAE684) GSK1838705A Repotrectinib (TPX-0005) AZD3463 AP26113-analog (ALK-IN-1) Ensartinib dihydrochloride ASP3026 HG-14-10-04 X-376 ALK inhibitor 1

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	Activity Description	PMID
NIH-3T3	Function assay	1 hr	Inhibition of human EML4-fused ALK F1174L mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 0.0002 μM.	24819116
NIH/3T3	Function assay		Inhibition of wild type EML4/ALK F1174L mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.0002 μM.	28431340
BAF3	Antiproliferative assay	72 hrs	Antiproliferative activity against mouse BAF3 cells harboring CD74-ROS1 after 72 hrs by SRB or CCK8 assay, IC50 = 0.0012 μM.	29288940
NIH-3T3	Function assay	1 hr	Inhibition of wild type human EML4-fused ALK expressed in mouse NIH-3T3 cells assessed as phosphorylated ALK level after 1 hr by sandwich ELISA, IC50 = 0.0013 μM.	24819116
NIH/3T3	Function assay		Inhibition of wild type EML4/ALK (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.0013 μM.	28431340
NIH-3T3	Function assay	1 hr	Inhibition of human EML4-fused ALK C1156Y mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 0.0016 μM.	24819116
NIH/3T3	Function assay		Inhibition of wild type EML4/ALK C1156Y mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.0016 μM.	28431340
BAF3	Antiproliferative assay	72 hrs	Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK after 72 hrs by SRB or CCK8 assay, IC50 = 0.0029 μM.	29288940
KARPAS299	Antiproliferative assay	72 hrs	Antiproliferative activity against human KARPAS299 cells harboring NPM-ALK after 72 hrs by SRB or CCK8 assay, IC50 = 0.003 μM.	29288940
NIH-3T3	Function assay	1 hr	Inhibition of human EML4-fused ALK S1206Y mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 0.0042 μM.	24819116
NIH/3T3	Function assay		Inhibition of wild type EML4/ALK S1206Y mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.0042 μM.	28431340
SU-DHL1	Antiproliferative assay	72 hrs	Antiproliferative activity against human SU-DHL1 cells harboring NPM-ALK after 72 hrs by SRB or CCK8 assay, IC50 = 0.0049 μM.	29288940
NCI-H3122	Antiproliferative assay	72 hrs	Antiproliferative activity against human NCI-H3122 cells after 72 hrs by SRB or CCK8 assay, IC50 = 0.0078 μM.	29288940
NIH-3T3	Function assay	1 hr	Inhibition of human EML4-fused ALK L1152R mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 0.009 μM.	24819116
NIH/3T3	Function assay		Inhibition of wild type EML4/ALK L1152R mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.009 μM.	28431340
NIH-3T3	Function assay	1 hr	Inhibition of human EML4-fused ALK G1269A mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 0.015 μM.	24819116
NIH/3T3	Function assay		Inhibition of wild type EML4/ALK G1269A mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.015 μM.	28431340
NIH-3T3	Function assay	1 hr	Inhibition of human EML4-fused ALK L1196M mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 0.021 μM.	24819116
NIH/3T3	Function assay		Inhibition of wild type EML4/ALK L1196M mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.021 μM.	28431340
NIH-3T3	Function assay	1 hr	Inhibition of human EML4-fused ALK 1151Tins mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 0.038 μM.	24819116
NIH/3T3	Function assay		Inhibition of wild type EML4/ALK 1151Tins mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.038 μM.	28431340
BAF3	Antiproliferative assay	72 hrs	Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK L1196M mutant after 72 hrs by SRB or CCK8 assay, IC50 = 0.0424 μM.	29288940
NIH-3T3	Function assay	1 hr	Inhibition of human EML4-fused ALK G1202R mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 0.077 μM.	24819116
NIH/3T3	Function assay		Inhibition of wild type EML4/ALK G1202R mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.077 μM.	28431340
BAF3	Antiproliferative assay	72 hrs	Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK G1202R mutant after 72 hrs by SRB or CCK8 assay, IC50 = 0.2 μM.	29288940
BAF3	Antiproliferative assay	72 hrs	Antiproliferative activity against mouse BAF3 cells harboring CD74-ROS1 G2032R mutant after 72 hrs by SRB or CCK8 assay, IC50 = 0.262 μM.	29288940
HCC78	Antiproliferative assay	72 hrs	Antiproliferative activity against human HCC78 cells harboring SLC34A2-ROS1 after 72 hrs by SRB or CCK8 assay, IC50 = 0.357 μM.	29288940
SU-DHL1	Function assay		Inhibition of ALK in human SU-DHL1 cells assessed as reduction in STAT3 phosphorylation at Y705 residue at 20 to 80 nM after 1 hr by Western blot analysis	29288940
SU-DHL1	Function assay		Inhibition of ALK in human SU-DHL1 cells assessed as reduction in Akt phosphorylation at S473 residue at 20 to 80 nM after 1 hr by Western blot analysis	29288940
SU-DHL1	Function assay		Inhibition of ALK phosphorylation at Y1278 residue in human SU-DHL1 cells at 20 to 80 nM after 1 hr by Western blot analysis	29288940
SU-DHL1	Function assay		Inhibition of ALK in human SU-DHL1 cells assessed as reduction in ERK phosphorylation at T202//Y204 residues at 20 to 80 nM after 1 hr by Western blot analysis	29288940
NCI-H3122	Function assay		Inhibition of ALK phosphorylation at Y1278 residue in human NCI-H3122 cells at 20 to 80 nM after 1 hr by Western blot analysis	29288940
NCI-H3122	Function assay		Inhibition of ALK in human NCI-H3122 cells assessed as reduction in STAT3 phosphorylation at Y705 residue at 20 to 80 nM after 1 hr by Western blot analysis	29288940
NCI-H3122	Function assay		Inhibition of ALK in human NCI-H3122 cells assessed as reduction in Akt phosphorylation at S473 residue at 20 to 80 nM after 1 hr by Western blot analysis	29288940
NCI-H3122	Function assay		Inhibition of ALK in human NCI-H3122 cells assessed as reduction in ERK phosphorylation at T202//Y204 residues at 20 to 80 nM after 1 hr by Western blot analysis	29288940
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 81 mg/mL (199.3 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 40.5 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	4.000mg/ml (9.84mM)	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.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.400mg/ml (0.98mM)	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.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Chemical Information, Storage & Stability

Molecular Weight	406.41	Formula	C₂₁H₁₉FN₆O₂	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1454846-35-5	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin 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

Mechanism of Action

Targets/IC₅₀/Ki	ROS1 (Cell-free assay) <0.02 nM(Ki) ALK (Cell-free assay) <0.07 nM(Ki) ALK (L1196M) (Cell-free assay) 0.07 nM(Ki) LTK (TYK1) (Cell-free assay) 2.7 nM FER (Cell-free assay) 3.3 nM FES (FPS) (Cell-free assay) 6 nM PTK2B (FAK2) (Cell-free assay) 14 nM TNK2 (ACK) (Cell-free assay) 17 nM PTK2 (FAK) (Cell-free assay) 17 nM NTRK2 (TRKB) (Cell-free assay) 23 nM NTRK1 (TRKA) (Cell-free assay) 24 nM NTRK3 (TRKC) (Cell-free assay) 46 nM FRK (PTK5) (Cell-free assay) 53 nM EGFR (ErbB1) T790M L858R (Cell-free assay) 245 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. 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. PF-06463922 also shows potent growth inhibitory activity and induces apoptosis in the NSCLC cells harboring either non-mutant ALK or mutant ALK fusions.
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%. 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. 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.
References	[1] https://pubmed.ncbi.nlm.nih.gov/24819116/ [2] http://mct.aacrjournals.org/content/12/11_Supplement/A277.short [3] http://mct.aacrjournals.org/content/12/11_Supplement/C253.short

Applications

Methods	Biomarkers	Images	PMID
Western blot	p-ALK / ALK		29650534

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT06378892	Recruiting	Non Small Cell Lung Cancer Metastatic\|ALK Gene Mutation	Centro di Riferimento Oncologico - Aviano	March 15 2024	Phase 2
NCT06092086	Recruiting	ALK Positive Non-small Cell Lung Cancer	Guangdong Association of Clinical Trials	August 18 2023	Phase 2
NCT05297890	Active not recruiting	Advanced or Metastatic ROS1-Positive Non-Small Cell Lung Cancer	CStone Pharmaceuticals\|Pfizer	May 27 2022	Phase 2
NCT05224609	Recruiting	Moderate Hepatic Impairment\|Severe Hepatic Impairment\|Healthy Volunteers	Pfizer	April 28 2022	Phase 1

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Frequently Asked Questions

Question 1:
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Answer:
For S7536, we recommend 2% DMSO+30% PEG 300+ddH2O (up to 5mg/ml) for its in vivo application.

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Lorlatinib (PF-6463922) ALK inhibitor

Chemical Structure

Molecular Weight: 406.41