1. Protein Tyrosine Kinase/RTK
    Apoptosis
  2. ALK
    ROS
    Apoptosis
  3. Lorlatinib

Lorlatinib (Synonyms: PF-06463922)

Cat. No.: HY-12215 Purity: 99.83%
Handling Instructions

Lorlatinib (PF-06463922) is a selective, orally active, brain-penetrant and ATP-competitive ROS1/ALK inhibitor. Lorlatinib has Kis of <0.025 nM, <0.07 nM, and 0.7 nM for ROS1, wild type ALK, and ALKL1196M, respectively. Lorlatinib has anticancer activity.

For research use only. We do not sell to patients.

Lorlatinib Chemical Structure

Lorlatinib Chemical Structure

CAS No. : 1454846-35-5

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 79 In-stock
Estimated Time of Arrival: December 31
5 mg USD 72 In-stock
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10 mg USD 108 In-stock
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25 mg USD 180 In-stock
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50 mg USD 288 In-stock
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100 mg USD 504 In-stock
Estimated Time of Arrival: December 31
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Customer Review

Based on 5 publication(s) in Google Scholar

Top Publications Citing Use of Products

    Lorlatinib purchased from MCE. Usage Cited in: Nat Commun. 2017 Oct 30;8(1):1197.

    Representative photographs (left) and quantification (right) of soft agar colony formation assay.
    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    Lorlatinib (PF-06463922) is a selective, orally active, brain-penetrant and ATP-competitive ROS1/ALK inhibitor. Lorlatinib has Kis of <0.025 nM, <0.07 nM, and 0.7 nM for ROS1, wild type ALK, and ALKL1196M, respectively. Lorlatinib has anticancer activity[1][2].

    IC50 & Target

    Ki: < 0.02 nM (ROS1), < 0.07 nM (ALK WT), 0.7 nM (ALK L1196M)

    In Vitro

    Lorlatinib (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]. Lorlatinib 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. Lorlatinib also shows potent growth inhibitory activity and induces apoptosis in the NSCLC cells harboring either non-mutant ALK or mutant ALK fusions[2].

    In Vivo

    In rats, Lorlatinib (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, Lorlatinib 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. Lorlatinib 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[2].

    Clinical Trial
    Molecular Weight

    406.41

    Formula

    C₂₁H₁₉FN₆O₂

    CAS No.

    1454846-35-5

    SMILES

    CN1C(C#N)=C2C(CN(C)C(C3=C([[email protected]@H](C)OC4=C(N)N=CC2=C4)C=C(F)C=C3)=O)=N1

    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 28 mg/mL (68.90 mM)

    H2O : < 0.1 mg/mL (insoluble)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.4606 mL 12.3028 mL 24.6057 mL
    5 mM 0.4921 mL 2.4606 mL 4.9211 mL
    10 mM 0.2461 mL 1.2303 mL 2.4606 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 2.5 mg/mL (6.15 mM); Clear solution

    • 2.

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

      Solubility: 2.5 mg/mL (6.15 mM); Suspended solution; Need ultrasonic

    • 3.

      Add each solvent one by one:  10% DMSO    90% corn oil

      Solubility: ≥ 2.5 mg/mL (6.15 mM); Clear solution

    *All of the co-solvents are provided by MCE.
    References
    Cell Assay
    [2]

    Cells are seeded in 96-well plates in growth medium containing 10% FBS and are cultured overnight at 37°C. The following day, serial dilutions of Lorlatinib or appropriate controls are added to the designated wells, and cells are incubated at 37°C for 72 h. A CellTiter-Glo assay is performed to determine the relative cell numbers. IC50 values are calculated by concentration-response curve fitting using a four-parameter analytical method.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2]

    De novoGBM tumorigenesis is initiated in LSL-FIG-ROS1;Cdkn2a−/−;LSL-Luc mice through intracranial stereotactic injections of Adeno-Cre as described previously. Tumor development is monitored using BLI as described below. Once tumors reach a given size (107 p-1·s-1·cm-2·sr-1), animals are randomLy enrolled into vehicle control or 3-, 7-, or 14-d treatment with the indicated doses of Lorlatinib. Drug is administered through s.c. implanted Alzet osmotic pumps. After treatment, mice are killed, GBM tumors are microdissected, and tissues are flash-frozen in liquid N2. The remaining brains are processed for histology.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References

    Purity: 99.83%

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    Keywords:

    LorlatinibPF-06463922PF06463922PF 06463922ALKROSApoptosisAnaplastic lymphoma kinaseALK tyrosine kinase receptorCD246Cluster of differentiation 246NSCLCNeuroblastomaCarcinomabrain-penetrantmutationthird-generationtyrosinekinaseInhibitorinhibitorinhibit

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