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

Lorlatinib (Synonyms: PF-06463922)

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

Lorlatinib (PF-06463922) is a potent, dual ALK/ROS1 inhibitor, with Kis of 0.02 nM, 0.07 nM, and 0.7 nM for ROS1, wild type ALK, and ALK-L1196M, respectively.

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
Estimated Time of Arrival: December 31
10 mg USD 108 In-stock
Estimated Time of Arrival: December 31
25 mg USD 180 In-stock
Estimated Time of Arrival: December 31
50 mg USD 288 In-stock
Estimated Time of Arrival: December 31
100 mg USD 504 In-stock
Estimated Time of Arrival: December 31
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500 mg   Get quote  

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Customer Review

Based on 4 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 potent, dual ALK/ROS1 inhibitor, with Kis of 0.02 nM, 0.07 nM, and 0.7 nM for ROS1, wild type ALK, and ALK-L1196M, respectively.

    IC50 & Target

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

    In Vitro

    Lorlatinib 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[2]. Lorlatinib 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, Lorlatinib 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[2]. In vivo, 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[3].

    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
    Kinase Assay
    [1]

    Recombinant human wild-type and mutant ALK kinase domain proteins (amino acids 1093–1411) are produced in-house using baculoviral expression, preactivated via autophosphorylation with MgATP, and assayed for kinase activity using a microfluidic mobility shift assay. The reactions contained 1.3 nM wild-type ALK or 0.5 nM mutant ALK (appropriate to produce 15-20% phosphorylation of peptide substrate after 1 h of reaction), 3 μM 5-FAM-KKSRGDYMTMQIG-CONH2), 5 mM MgCl2, and the Km level of ATP in 25 mM Hepes, pH 7.1. The inhibitors are shown to be ATP-competitive from kinetic and crystallographic studies. The Ki values are calculated by fitting the conversion (%) to a competitive inhibition equation. ROS1 enzyme is assayed as described above for ALK, except using 0.25 nM recombinant human ROS1 catalytic domain (amino acids 1883-2347). Kinase inhibitor selectivity is evaluated using a 206-kinase panel.

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

    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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    Product Name:
    Lorlatinib
    Cat. No.:
    HY-12215
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