Lorlatinib (PF-6463922)

For research use only.

Catalog No.S7536

19 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.

Size Price Stock Quantity  
USD 197 In stock
USD 797 In stock
Bulk Discount
Bulk Inquiry

Free Overnight Delivery on orders over $ 500
Next day delivery by 10:00 a.m. Order now.

Selleck's Lorlatinib (PF-6463922) has been cited by 19 publications

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. 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 NFrTNnZHfW6ldHnvckBie3OjeR?= Ml:2NUBp M1jRRmlvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugSlEyPzSOIH31eIFvfCCneIDy[ZN{\WRiaX6gcY92e2ViTlnIMVNVOyClZXzsd{Bie3Onc4Pl[EBieyCyaH;zdIhwNUGOSzDs[ZZmdCCjZoTldkAyKGi{IHL5JJNidmS5aXPoJGVNUVOD NYq3Z5R4OjR6MUmxNVY>

... 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 CC1OC2=C(N)N=CC(=C2)C3=C(C#N)[N](C)N=C3CN(C)C(=O)C4=C1C=C(F)C=C4

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation (Different batches have different solubility ratios, please contact Selleck to provide you with the correct ratio)
% DMSO % % Tween 80 % ddH2O
CalculateReset

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

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.

Molarity Calculator

Mass Concentration Volume Molecular Weight

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

If you have any other enquiries, please leave a message.

  • * Indicates a Required Field

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

Related ALK Products

  • Erlotinib New

    Erlotinib is an EGFR inhibitor with IC50 of 2 nM, >1000-fold more sensitive for EGFR than human c-Src or v-Abl. Erlotinib induces autophagy.

  • Bemcentinib（R428) New

    R428 (BGB324) is an inhibitor of Axl with IC50 of 14 nM, >100-fold selective for Axl versus Abl. Selectivty for Axl is also greater than Mer and Tyro3 (50-to-100- fold more selective) and InsR, EGFR, HER2, and PDGFRβ (100- fold more selective).

  • Pexidartinib (PLX3397) New

    Pexidartinib (PLX3397) is an oral, potent mutil-targeted receptor tyrosine kinase inhibitor of CSF-1R, Kit, and FLT3 with IC50 of 20 nM, 10 nM and 160 nM, respectively. Pexidartinib (PLX3397) induces apoptosis and necrosis with antitumor activity. Phase 3.

  • TAE684 (NVP-TAE684)

    TAE684 (NVP-TAE684) is a potent and selective ALK inhibitor with IC50 of 3 nM in a cell-free assay, 100-fold more sensitive for ALK than InsR.

  • GSK1838705A

    GSK1838705A is a potent IGF-1R inhibitor with IC50 of 2.0 nM, modestly potent to IR and ALK with IC50 of 1.6 nM and 0.5 nM, respectively, and little activity to other protein kinases.

    Features:A small-molecule kinase inhibitor of IGF-1R and the insulin receptor.

  • Alectinib (CH5424802)

    Alectinib (CH5424802) is a potent ALK inhibitor with IC50 of 1.9 nM in cell-free assays, sensitive to L1196M mutation and higher selectivity for ALK than PF-02341066, NVP-TAE684 and PHA-E429.

  • AP26113-analog (ALK-IN-1)

    AP26113-analog (ALK-IN-1) is an analog of AP26113 which is a potent and selective ALK inhibitor. It is also an inhibitor of EGFR.

    Features:At least 10-fold more potent and selective in ALK inhibition relative to crizotinib.

  • ASP3026

    ASP3026 is a novel and selective inhibitor for ALK with IC50 of 3.5 nM. Phase 1.

  • AZD3463

    AZD3463 is a novel orally bioavailable ALK inhibitor with Ki of 0.75 nM, which also inhibits IGF1R with equivalent potency.

  • Ceritinib (LDK378)

    Ceritinib (LDK378) is potent inhibitor against ALK with IC50 of 0.2 nM in cell-free assays. Ceritinib (LDK378) also inhibits IGF-1R, InsR, STK22D and FLT3 with IC50 of 8 nM, 7 nM, 23 nM and 60 nM, respectively. Phase 3.

    Features:Does not cross react with c-Met, and has an improved in vivo glucose homeostasis profile relative to TAE684. May be active in Crizotinib-relapsed tumors.

Tags: buy Lorlatinib (PF-6463922) | Lorlatinib (PF-6463922) supplier | purchase Lorlatinib (PF-6463922) | Lorlatinib (PF-6463922) cost | Lorlatinib (PF-6463922) manufacturer | order Lorlatinib (PF-6463922) | Lorlatinib (PF-6463922) distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID