Lorlatinib
Based on 38 publication(s) in Google Scholar
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.
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Pureté: 99.99%
- CAS No.: 1454846-35-5
- Formule: C21H19FN6O2
- Masse moléculaire:406.41
-
Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
Publications Citing Use of MedChemExpress (MCE) Lorlatinib
More- Cancer Cell. 2026 May 11;44(5):983-994.e5. [Abstract]
- Cancer Discov. 2024 Dec 2;14(12):2367-2386. [Abstract]
- Nat Cancer. 2022 Oct;3(10):1211-1227. [Abstract]
- Cancer Res. 2022 Feb 1;82(3):484-496. [Abstract]
- Nat Commun. 2024 Apr 23;15(1):3422. [Abstract]
- Nat Commun. 2017 Oct 30;8(1):1197. [Abstract]
- Cell Rep Med. 2023 Feb 21;4(2):100911. [Abstract]
- Cancer Lett. 2026 May 29:656:218624. [Abstract]
- J Exp Med. 2024 Mar 4;221(3):e20232028. [Abstract]
- Oncogene. 2022 Sep;41(40):4547-4559. [Abstract]
- Oncogene. 2022 May;41(20):2789-2797. [Abstract]
- Leukemia. 2025 Aug 14. [Abstract]
- EMBO Mol Med. 2020 Jul 7;12(7):e11099. [Abstract]
- J Med Chem. 2024 Oct 24;67(20):18098-18123. [Abstract]
- Mol Syst Biol. 2024 Jan;20(1):28-55. [Abstract]
- Sci Rep. 2024 Sep 27;14(1):22191. [Abstract]
- Mol Pharm. 2023 Jan 2;20(1):357-369. [Abstract]
- Cancers (Basel). 2026 May 14;18(10):1591. [Abstract]
- Cancers (Basel). 2021 Dec 29;14(1):151. [Abstract]
- iScience. 2024 Apr 23;27(5):109800. [Abstract]
- Bioengineering (Basel). 2025 Oct 19;12(10):1121. [Abstract]
- Cancer Res Commun. 2023 Dec 27;3(12):2608-2622. [Abstract]
- Cancer Med. 2020 Jun;9(12):4350-4359. [Abstract]
- J Pharm Biomed Anal. 2021 Jan 30:193:113733. [Abstract]
- Mol Pharmacol. 2022 Jun;101(6):381-389. [Abstract]
- Fundam Clin Pharmacol. 2021 Oct;35(5):919-929. [Abstract]
- J Chromatogr B Analyt Technol Biomed Life Sci. 2025 Dec 15:1267:124770. [Abstract]
- Eur J Drug Metab Pharmacokinet. 2021 Sep;46(5):625-635. [Abstract]
- J Anal Methods Chem. 2019 Mar 4:2019:7574369. [Abstract]
- Biomed Chromatogr. 2024 Oct;38(10):e5986. [Abstract]
- Biomed Chromatogr. 2023 Jun;37(6):e5628. [Abstract]
- bioRxiv. 2026 Jan 27.
- bioRxiv. 2026 Jan 23:2026.01.21.700721. [Abstract]
- bioRxiv. 2025 Dec 5.
- Maastricht University. 2023 Jun 1.
- Universitat Autònoma de Barcelona. 2022 Aug.
- Uppsala University. 2022 Feb.
- bioRxiv. October 28, 2021.
-
In Vivo Efficacy Study
-
Cell Proliferation/Viability Assay
-
Cell Imaging/Staining
-
WB
-
Cell Proliferation/Viability Assay
Activité biologique
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]
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| BaF3 | IC50 |
1.2 nM
Compound: 5
|
Antiproliferative activity against mouse BAF3 cells harboring CD74-ROS1 after 72 hrs by SRB or CCK8 assay
Antiproliferative activity against mouse BAF3 cells harboring CD74-ROS1 after 72 hrs by SRB or CCK8 assay
|
[PMID: 29288940] |
| BaF3 | IC50 |
2.9 nM
Compound: 5
|
Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK after 72 hrs by SRB or CCK8 assay
Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK after 72 hrs by SRB or CCK8 assay
|
[PMID: 29288940] |
| BaF3 | IC50 |
200 nM
Compound: 5
|
Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK G1202R mutant after 72 hrs by SRB or CCK8 assay
Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK G1202R mutant after 72 hrs by SRB or CCK8 assay
|
[PMID: 29288940] |
| BaF3 | IC50 |
262 nM
Compound: 5
|
Antiproliferative activity against mouse BAF3 cells harboring CD74-ROS1 G2032R mutant after 72 hrs by SRB or CCK8 assay
Antiproliferative activity against mouse BAF3 cells harboring CD74-ROS1 G2032R mutant after 72 hrs by SRB or CCK8 assay
|
[PMID: 29288940] |
| BaF3 | IC50 |
42.4 nM
Compound: 5
|
Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK L1196M mutant after 72 hrs by SRB or CCK8 assay
Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK L1196M mutant after 72 hrs by SRB or CCK8 assay
|
[PMID: 29288940] |
| BaF3 | IC50 |
>1000 nM
Compound: 5
|
Antiproliferative activity against IL3-stimulated mouse BAF3 cells after 72 hrs by SRB or CCK8 assay
Antiproliferative activity against IL3-stimulated mouse BAF3 cells after 72 hrs by SRB or CCK8 assay
|
[PMID: 29288940] |
| HCC78 | IC50 |
357 nM
Compound: 5
|
Antiproliferative activity against human HCC78 cells harboring SLC34A2-ROS1 after 72 hrs by SRB or CCK8 assay
Antiproliferative activity against human HCC78 cells harboring SLC34A2-ROS1 after 72 hrs by SRB or CCK8 assay
|
[PMID: 29288940] |
| KARPAS-299 | IC50 |
3 nM
Compound: 5
|
Antiproliferative activity against human KARPAS299 cells harboring NPM-ALK after 72 hrs by SRB or CCK8 assay
Antiproliferative activity against human KARPAS299 cells harboring NPM-ALK after 72 hrs by SRB or CCK8 assay
|
[PMID: 29288940] |
| NCI-H3122 | IC50 |
7.8 nM
Compound: 5
|
Antiproliferative activity against human NCI-H3122 cells after 72 hrs by SRB or CCK8 assay
Antiproliferative activity against human NCI-H3122 cells after 72 hrs by SRB or CCK8 assay
|
[PMID: 29288940] |
| NIH3T3 | IC50 |
0.2 nM
Compound: 8k, PF-06463922
|
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
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
|
[PMID: 24819116] |
| NIH3T3 | IC50 |
1.3 nM
Compound: 8k, PF-06463922
|
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
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
|
[PMID: 24819116] |
| NIH3T3 | IC50 |
1.6 nM
Compound: 8k, PF-06463922
|
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
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
|
[PMID: 24819116] |
| NIH3T3 | IC50 |
15 nM
Compound: 8k, PF-06463922
|
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
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
|
[PMID: 24819116] |
| NIH3T3 | IC50 |
21 nM
Compound: 8k, PF-06463922
|
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
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
|
[PMID: 24819116] |
| NIH3T3 | IC50 |
38 nM
Compound: 8k, PF-06463922
|
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
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
|
[PMID: 24819116] |
| NIH3T3 | IC50 |
4.2 nM
Compound: 8k, PF-06463922
|
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
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
|
[PMID: 24819116] |
| NIH3T3 | IC50 |
77 nM
Compound: 8k, PF-06463922
|
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
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
|
[PMID: 24819116] |
| NIH3T3 | IC50 |
9 nM
Compound: 8k, PF-06463922
|
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
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
|
[PMID: 24819116] |
| SU-DHL-1 | IC50 |
4.9 nM
Compound: 5
|
Antiproliferative activity against human SU-DHL1 cells harboring NPM-ALK after 72 hrs by SRB or CCK8 assay
Antiproliferative activity against human SU-DHL1 cells harboring NPM-ALK after 72 hrs by SRB or CCK8 assay
|
[PMID: 29288940] |
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.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
-
CAS No. 1454846-35-5
-
Appearance Solid
-
Masse moléculaire 406.41
-
Formule C21H19FN6O2
-
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
-
Synonyms
PF-06463922
-
Livraison
Room temperature in continental US; may vary elsewhere.
-
Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (38)
-
Journal Impact Factor
-
Most Recent
-
Cancer Cell
JYP0322, a highly selective and brain-penetrant ROS1 inhibitor, overcomes ROS1G2032R resistance mutation in NSCLC: The first-in-human phase 1 trial. [Abstract]2026 May 11;44(5):983-994.e5. PMID: 42030931 -
Cancer Discov
NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations. [Abstract]2024 Dec 2;14(12):2367-2386. PMID: 39269178
Lorlatinib purchased from MedChemExpress. Usage Cited in: Cancer Discov. 2024 Dec 2;14(12):2367-2386. [Abstract]
Lorlatinib (10 mg/kg; oral; daily). Change in tumor volume over time plotted as mean ± SEM for models harboring ALK fusion with a WT kinase domain.
-
Nat Cancer
Targeting the ALK-CDK9-Tyr19 kinase cascade sensitizes ovarian and breast tumors to PARP inhibition via destabilization of the P-TEFb complex. [Abstract]2022 Oct;3(10):1211-1227. PMID: 36253486
Lorlatinib purchased from MedChemExpress. Usage Cited in: Nat Cancer. 2022 Oct;3(10):1211-1227. [Abstract]
Representative images of clonogenic assay results in PARP inhibitor (PARPi)-resistant OVCA433 cell in the presence of the indicated inhibitor for 12 d. ALKi, ALK inhibitor; LOR, Lorlatinib (250-500 nM); TALA, Talazoparib (100-200 nM); Comb, combination of Lorlatinib and Talazoparib.
Lorlatinib purchased from MedChemExpress. Usage Cited in: Nat Cancer. 2022 Oct;3(10):1211-1227. [Abstract]
Representative images of RAD51 with EdU/DAPI staining in OVCA433 cell treated with 0.25 μM PARP inhibitor (PARPi; Talazoparib) or 0.5 μM ALK inhibitor (ALKi; Lorlatinib), either alone or in combination, for 48 h.
Lorlatinib purchased from MedChemExpress. Usage Cited in: Nat Cancer. 2022 Oct;3(10):1211-1227. [Abstract]
WB of indicated proteins in cells treated with or without 0.5 μM ALK inhibitor (Lorlatinib) for 24 h.
-
Cancer Res
2022 Feb 1;82(3):484-496. PMID: 34853072 -
Nat Commun
Targeting NRAS via miR-1304-5p or farnesyltransferase inhibition confers sensitivity to ALK inhibitors in ALK-mutant neuroblastoma. [Abstract]2024 Apr 23;15(1):3422. PMID: 38653965 -
Nat Commun
Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions. [Abstract]2017 Oct 30;8(1):1197. PMID: 29084941
Lorlatinib purchased from MedChemExpress. Usage Cited in: Nat Commun. 2017 Oct 30;8(1):1197. [Abstract]
Lorlatinib (100 nM; 72 h). Representative photographs of soft agar colony formation assay.
-
Cell Rep Med
Using patient-derived organoids to predict locally advanced or metastatic lung cancer tumor response: A real-world study. [Abstract]2023 Feb 21;4(2):100911. PMID: 36657446 -
Cancer Lett
Integrated clinical, genomic and functional characterization of a novel ALK variant in neuroblastoma. [Abstract]2026 May 29:656:218624. PMID: 42217560 -
J Exp Med
2024 Mar 4;221(3):e20232028. PMID: 38284990 -
Oncogene
ALK fusion promotes metabolic reprogramming of cancer cells by transcriptionally upregulating PFKFB3. [Abstract]2022 Sep;41(40):4547-4559. PMID: 36064579 -
Oncogene
2022 May;41(20):2789-2797. PMID: 35411036 -
Leukemia
Unraveling the impact of crizotinib to promote megakaryopoiesis for alleviating thrombocytopenia in myelodysplastic neoplasms. [Abstract]2025 Aug 14. PMID: 40813622 -
EMBO Mol Med
Vulnerability of drug-resistant EML4-ALK rearranged lung cancer to transcriptional inhibition. [Abstract]2020 Jul 7;12(7):e11099. PMID: 32558295 -
J Med Chem
Discovery of Oral Degraders of the ROS1 Fusion Protein with Potent Activity against Secondary Resistance Mutations. [Abstract]2024 Oct 24;67(20):18098-18123. PMID: 39361251 -
Mol Syst Biol
Illuminating phenotypic drug responses of sarcoma cells to kinase inhibitors by phosphoproteomics. [Abstract]2024 Jan;20(1):28-55. PMID: 38177929 -
Sci Rep
Novel insight into mechanisms of ROS1 catalytic activation via loss of the extracellular domain. [Abstract]2024 Sep 27;14(1):22191. PMID: 39333184 -
Mol Pharm
Dynamic Changes in Gastrointestinal Fluid Characteristics after Food Ingestion Are Important for Quantitatively Predicting the In Vivo Performance of Oral Solid Dosage Forms in Humans in the Fed State. [Abstract]2023 Jan 2;20(1):357-369. PMID: 36373973 -
Cancers (Basel)
A Zinc Finger Protein-Based Prognostic Model in Lung Adenocarcinoma Identifies FGD3 as a Marker Associated with Lorlatinib Resistance. [Abstract]2026 May 14;18(10):1591. PMID: 42192951 -
Cancers (Basel)
BRG1 and NPM-ALK Are Co-Regulated in Anaplastic Large-Cell Lymphoma; BRG1 Is a Potential Therapeutic Target in ALCL. [Abstract]2021 Dec 29;14(1):151. PMID: 35008316 -
iScience
ALK inhibitors suppress HCC and synergize with anti-PD-1 therapy and ABT-263 in preclinical models. [Abstract]2024 Apr 23;27(5):109800. PMID: 38741708 -
Bioengineering (Basel)
Precision Oncology for High-Grade Gliomas: A Tumor Organoid Model for Adjuvant Treatment Selection. [Abstract]2025 Oct 19;12(10):1121. PMID: 41155119 -
Cancer Res Commun
SHP2 inhibition with TNO155 increases efficacy and overcomes resistance of ALK inhibitors in neuroblastoma. [Abstract]2023 Dec 27;3(12):2608-2622. PMID: 38032104 -
Cancer Med
The underlying mechanisms of lorlatinib penetration across the blood-brain barrier and the distribution characteristics of lorlatinib in the brain. [Abstract]2020 Jun;9(12):4350-4359. PMID: 32347012 -
J Pharm Biomed Anal
To quantify the small-molecule kinase inhibitors ceritinib, dacomitinib, lorlatinib, and nintedanib in human plasma by liquid chromatography/triple-quadrupole mass spectrometry. [Abstract]2021 Jan 30:193:113733. PMID: 33217707 -
Mol Pharmacol
Influence of Tyrosine Kinase Inhibition on Organic Anion Transporting Polypeptide 1B3-Mediated Uptake. [Abstract]2022 Jun;101(6):381-389. PMID: 35383108 -
Fundam Clin Pharmacol
2021 Oct;35(5):919-929. PMID: 33523504 -
J Chromatogr B Analyt Technol Biomed Life Sci
Development of a validated and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to simultaneous determination of crizotinib, alectinib and lorlatinib in human plasma. [Abstract]2025 Dec 15:1267:124770. PMID: 40902417 -
Eur J Drug Metab Pharmacokinet
Differential Inhibition of Equilibrative Nucleoside Transporter 1 (ENT1) Activity by Tyrosine Kinase Inhibitors. [Abstract]2021 Sep;46(5):625-635. PMID: 34275128 -
J Anal Methods Chem
Pharmacokinetic Study and Tissue Distribution of Lorlatinib in Mouse Serum and Tissue Samples by Liquid Chromatography-Mass Spectrometry. [Abstract]2019 Mar 4:2019:7574369. PMID: 30949374 -
Biomed Chromatogr
Development and validation of an ultra-performance liquid chromatography-tandem mass spectrometry method to quantify the small molecule inhibitors adagrasib, alectinib, brigatinib, capmatinib, crizotinib, lorlatinib, selpercatinib, and sotorasib in human plasma. [Abstract]2024 Oct;38(10):e5986. PMID: 39136165 -
Biomed Chromatogr
Development and validation of an HPLC-MS/MS method to simultaneously quantify brigatinib, lorlatinib, pralsetinib and selpercatinib in human K2-EDTA plasma. [Abstract]2023 Jun;37(6):e5628. PMID: 36941218 -
-
bioRxiv
2026 Jan 23:2026.01.21.700721. PMID: 41648424 -
-
-
-
-
Solvant et solubilité
DMSO : ≥ 28 mg/mL (68.90 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
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
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
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
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
For the following dissolution methods, please prepare the working solution directly:
It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 50% PEG300 50% Saline
Solubility: 5 mg/mL (12.30 mM); Clear solution; Need ultrasonic
Add each solvent one by one: 0.5% CMC/saline water
Solubility: 1 mg/mL (2.46 mM); Suspended solution; Need ultrasonic
Please enter the basic information of animal experiments:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
-
%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
-
%+
-
+%Tween-80 + +
-
%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocole
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.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Pureté et documentation
-
Fiche technique (285 KB)
-
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
-
Instruction de manipulation (2659 KB)
Références
[1]. Zou HY, et al. PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models. Cancer Cell. 2015 Jul 13;28(1):70-81. [Content Brief]
[2]. Johnson TW, et al. Discovery of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations. J Med Chem. 2014 Jun 12;57(11):4720-44. [Content Brief]
[3]. Zou HY, et al. PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking PF-02341066-resistant ROS1 mutations. Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3493-8 [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.4606 mL | 12.3028 mL | 24.6057 mL | 61.5142 mL |
| 5 mM | 0.4921 mL | 2.4606 mL | 4.9211 mL | 12.3028 mL | |
| 10 mM | 0.2461 mL | 1.2303 mL | 2.4606 mL | 6.1514 mL | |
| 15 mM | 0.1640 mL | 0.8202 mL | 1.6404 mL | 4.1009 mL | |
| 20 mM | 0.1230 mL | 0.6151 mL | 1.2303 mL | 3.0757 mL | |
| 25 mM | 0.0984 mL | 0.4921 mL | 0.9842 mL | 2.4606 mL | |
| 30 mM | 0.0820 mL | 0.4101 mL | 0.8202 mL | 2.0505 mL | |
| 40 mM | 0.0615 mL | 0.3076 mL | 0.6151 mL | 1.5379 mL | |
| 50 mM | 0.0492 mL | 0.2461 mL | 0.4921 mL | 1.2303 mL | |
| 60 mM | 0.0410 mL | 0.2050 mL | 0.4101 mL | 1.0252 mL |