1. Protein Tyrosine Kinase/RTK Apoptosis
  2. Anaplastic lymphoma kinase (ALK) ROS Kinase Apoptosis
  3. Lorlatinib

Lorlatinib  (Synonyms: PF-06463922)

Cat. No.: HY-12215 Purity: 99.92%
COA Handling Instructions

Lorlatinib (PF-06463922) is a selective, orally active, brain-penetrant and ATP-competitive ROS1/ALK inhibitor with anticancer activity. Lorlatinib has Kis of <0.025 nM, <0.07 nM, and 0.7 nM for ROS1, wild type ALK, and ALKL1196M, respectively. Lorlatinib targets to EML4-ALK, and inhibits ALK phosphorylation with IC50s of 15-43 nM (ALKL1196), 14-80 nM (ALKG1269A), 38-50 nM (ALK1151Tins), 77-113 nM (ALKG1202R), 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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Solid + Solvent
10 mM * 1 mL in DMSO
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10 mM * 1 mL in DMSO USD 79 In-stock
Solid
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10 mg USD 108 In-stock
25 mg USD 180 In-stock
50 mg USD 288 In-stock
100 mg USD 504 In-stock
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Customer Review

Based on 23 publication(s) in Google Scholar

Top Publications Citing Use of Products

    Lorlatinib purchased from MedChemExpress. Usage Cited in: Nat Commun. 2017 Oct 30;8(1):1197.  [Abstract]

    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 with anticancer activity. Lorlatinib has Kis of <0.025 nM, <0.07 nM, and 0.7 nM for ROS1, wild type ALK, and ALKL1196M, respectively. Lorlatinib targets to EML4-ALK, and inhibits ALK phosphorylation with IC50s of 15-43 nM (ALKL1196), 14-80 nM (ALKG1269A), 38-50 nM (ALK1151Tins), 77-113 nM (ALKG1202R), respectively[1][2][3].

    IC50 & Target

    IC50: 15-43 nM (ALKL1196), 14-80 nM (ALKG1269A), 38-50 nM (ALK1151Tins), 77-113 nM (ALKG1202R)[3]
    Ki: <0.07 nM (ALKWT), 0.6 nM (ALKL1996M), 0.9 nM (ALKG1269A), 0.1 nM (ALK1151Tins), <0.1 nM (ALKL1152R), 0.2 nM (ALKS1206Y), <0.1 nM (ALKC1156Y), <0.1nM (ALKF1174L)[3]

    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].

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

    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].

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

    Clinical Trial
    Molecular Weight

    406.41

    Formula

    C21H19FN6O2

    CAS No.
    Appearance

    Solid

    Color

    White to off-white

    SMILES

    CN1C(C#N)=C2C(CN(C)C(C3=C([C@@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 2 years
    -20°C 1 year
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 28 mg/mL (68.90 mM)

    *"≥" 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:  50% PEG300    50% Saline

      Solubility: 5 mg/mL (12.30 mM); Clear solution; Need ultrasonic

    • 2.

      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

    • 3.

      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

    • 4.

      Add each solvent one by one:  10% DMSO    90% Corn Oil

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

    • 5.

      Add each solvent one by one:  5% DMSO    40% PEG300    5% Tween-80    50% Saline

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

    • 6.

      Add each solvent one by one:  0.5% CMC/saline water

      Solubility: 1 mg/mL (2.46 mM); Suspended solution; Need ultrasonic

    *All of the co-solvents are available by MedChemExpress (MCE).
    Purity & Documentation

    Purity: 99.92%

    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
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    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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