Ligritinib
Based on 1 Customer Validation
Ligritinib (AB801) is an orally active AXL receptor tyrosine kinase inhibitor, with a IC50 of 1.8 nM, Ki of 0.024 nM, and Kd of 0.093 nM against human targets. It exhibits broad selectivity against the human kinome, including high selectivity for MERTK and TYRO3. Ligritinib blocks the AXL signaling pathway independent of dimerization inducers, and acts as both a tumor growth inhibitor and an AXL inducer. Ligritinib can be used in research related to clear cell renal cell carcinoma, advanced solid tumors, and non-small cell lung cancer.
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- Purity : 98.08%
- CAS No.: 3024588-48-2
- 화학식: C33H32N6O
- 분자량:528.65
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
Biological Activity
제품 설명
IC50 & Target
[1]|
Axl 1.8 nM (IC50) |
Axl 0.024 nM (Ki) |
Axl 0.093 nM (Kd) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK-293T | IC50 |
68 nM
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Inhibition of AXL autophosphorylation in transiently transfected human HEK293T cells incubated for 1 h in 100% human serum, measured via pAXL ELISA with NanoLuc activity readout.
Inhibition of AXL autophosphorylation in transiently transfected human HEK293T cells incubated for 1 h in 100% human serum, measured via pAXL ELISA with NanoLuc activity readout.
|
40407274 |
In Vitro
Ligritinib (1 h) inhibits the autophosphorylation of AXL in transiently transfected HEK293T cells, with an IC50 of 68 nM in 100% human serum[1].
Ligritinib (10 μM) inhibits hERG channels by 46%[1].
Ligritinib exhibits limited direct inhibitory effects on human CYP isoenzymes, with its IC50 values ranging from 5.6 μM (CYP3A4-T) to >100 μM (CYP1A2, CYP2B6)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Nu/Nu (female, 6-10 weeks old, human clear-cell renal cell carcinoma 786-O xenograft model via subcutaneous injection of 4 × 106 cells in right flank)[1]
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Dosage:10 mg/kg; 30 mg/kg
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Administration:p.o.; daily
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Result:Did not result in tumor growth inhibition compared to vehicle control when administered as single-agent at 10 mg/kg or 30 mg/kg.
Caused a statistically significant reduction in tumor volume compared to vehicle, single-agent sunitinib, or single-agent Ligritinib when combined with Sunitinib at 30 mg/kg.
Showed statistically significant tumor growth inhibition compared to vehicle control but not compared to single-agent Sunitinib or Ligritinib when combined with sunitinib at 10 mg/kg.
Significantly increased plasma levels of soluble AXL at 30 mg/kg, indicative of AXL inhibition.
Was well-tolerated, with no significant loss of body weight observed.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 3024588-48-2
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Appearance Solid
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분자량 528.65
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화학식 C33H32N6O
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Color Off-white to pink
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SMILES
CC(C=CC=N1)=C1C(C=N2)=CC=C2C3=NNC4=NC=C(C=C43)C5=CC6=C(C=C5)CC[C@@H](CC6)N7C8COCC7C8
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Synonyms
AB801
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Protocol
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Patient-Derived Xenograft (PDX)
Patient-derived xenograft (PDX) models are generated by engrafting primary human tumor tissue directly into immunodeficient mice, allowing in vivo propagation of patient tumor biology without initial in vitro adaptation. These models are used to preserve key histopathological and molecular characteristics of the original tumor and enable assessment of tumor growth dynamics and therapeutic response in a living organism. The biological readout is tumor engraftment and subsequent growth in the murine host, which reflects the ability of human tumor cells to survive, vascularize, and expand in an immunocompromised microenvironment.
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Patient-Derived Orthotopic Xenograft (PDOX)
Patient-derived orthotopic xenograft (PDOX) modeling implants fresh patient tumor tissue or patient-derived tumor cells into the anatomically corresponding organ or tissue site of immunodeficient mice, usually by surgical orthotopic implantation, to preserve patient tumor histology, local microenvironmental context, invasion, metastatic behavior, and treatment-response features better than subcutaneous implantation. PDOX readouts include tumor engraftment, orthotopic tumor growth, local invasion, metastasis, recurrence after resection, histologic similarity to the donor tumor, biomarker retention, molecular concordance, survival, and response or resistance to therapy. PDOX models are used for preclinical drug testing and individualized therapy evaluation, but engraftment success varies by tumor type and specimen quality.
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Subcutaneous Cell-Line-Derived Xenograft
Subcutaneous cell-line-derived xenograft (CDX) models are established by implanting cultured human cancer cell lines into immunodeficient mice, where the injected cells form localized tumors that can be monitored in vivo as a measure of tumorigenic potential, growth kinetics, and treatment response. These models are widely used in oncology research because they allow reproducible tumor formation and enable comparative assessment of tumor growth between different cell lines or genetic manipulations in a controlled in vivo microenvironment. Subcutaneous implantation of cancer cells in immunodeficient mice is a standard approach for evaluating tumor growth behavior and therapeutic response across multiple cancer types, including prostate, esophageal, pancreatic, and colon cancer models.
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Orthotopic Cell-Line Xenograft
Orthotopic cell-line xenograft models involve implantation of human cancer cell lines into the anatomically corresponding organ of immunodeficient mice to reproduce tumor growth within a native microenvironment, enabling more clinically relevant tumor behavior compared with subcutaneous models. These models are widely used because orthotopic placement better recapitulates tumor progression, including invasion and metastatic spread, which are often underrepresented in heterotopic implantation systems. Compared with conventional xenografts, orthotopic implantation is described as more technically complex but provides improved simulation of tumor-microenvironment interactions and metastatic behavior, making it particularly valuable for translational oncology research. Surgical orthotopic implantation approaches have been emphasized as enabling faithful reproduction of clinical cancer features, including metastasis and disease progression patterns that align with the tumor’s organ of origi
순도&문서
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Data Sheet (293 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
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- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Handling Instructions (2659 KB)
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)