Axl-IN-21
Axl-IN-21 is an orally active and selective AXL inhibitor (Kd = 2.7 nM, IC50 = 4.0 nM). Axl-IN-21 displays kinase selectivity and retains strong activity against cancer-related mul-kinases (Mer with Kd = 1.4 nM, DDR1 with IC50 = 22.2 nM, HIPK4 with Kd = 11.0 nM and LOK with Kd =10 nM). Axl-IN-21 overcomes tumor microenvironment-driven resistance by blocking CAF-derived GAS6-induced AXL/STAT3/ABCG1 signaling, restoring chemosensitivity and inhibiting drug efflux in gastric cancer (GC). Axl-IN-21 suppresses TGF-β1-induced epithelial-mesenchymal transition (EMT), migration, and invasion in MDA-MB-231 cells. Axl-IN-21 exhibits no significant cytotoxicity in non-cancerous cells. Axl-IN-21 can be research for triple negative breast cancer and gastric cancer[1] [2] .
For research use only. We do not sell to patients.
- CAS No.: 1958081-87-2
- Formula: C30H27FN4O5
- Molecular Weight:542.56
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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DDR1 22.2 nM (IC50) |
Mer 1.4 nM (Kd) |
Axl 4 nM (IC50) |
Axl 2.7 nM (Kd) |
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Cell Line
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Type | Value | Description | References |
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| 4T1 | IC50 |
10 μM
Compound: 9im
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Antiproliferative activity against mouse 4T1 cells over-expressing Axl cells after 24 to 72 hrs by CCK8 assay
Antiproliferative activity against mouse 4T1 cells over-expressing Axl cells after 24 to 72 hrs by CCK8 assay
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[PMID: 27379978] |
Axl-IN-21 (compound 9im) (0.1-0.5 μM) dose-dependently inhibits AXL phosphorylation and reverses the epithelial-mesenchymal transition (restoring E cadherin and reducing N cadherin expression) in SNU668 and MKN1 gastric cancer cells, even when co cultured with cancer-associated fibroblasts (CAF), restores chemosensitivity by blocking CAF induced AXL activation and downstream signaling, although co culture with CAFs normally reduces apoptotic markers (cleaved PARP and cleaved caspase 3) following chemotherapy including 5-Fluorouracil (5 FU) (HY-90006) and cisplatin (HY-17394)[1].
Axl-IN-21 (0.5-32 μM) exhibits lower cytotoxicity in non-cancerous cells compared to BGB324 (HY-15150) [1].
Axl-IN-21 (0.1-0.5 μM) inhibits JAK1/STAT3, PI3K/AKT and MEK/ERK signalling pathways and reduces the CAF)-induced enhancement of cell migration in SNU668 cells co-cultured with CAFs, even in the presence of CAF-conditioned media or direct co-culture. [1].
Axl-IN-21 (0.5-2 μM) suppresses CAF-induced AXL activation, downstream signalling, GC cell migration and chemoresistance in inhibiting AXL phosphorylation in SNU668 cocultured with CAFs and/or treated with chemotherapeutic agents[1].
Axl-IN-21 (0.1-0.5 μM) suppresses both the upregulation of ABCG1 expression and the phosphorylation of AXL, JAK1/STAT3, PI3K/AKT, and MEK/ERK in AXL-activated GC SNU668 cells treated with recombinant GAS6[1].
Axl-IN-21 decreased ABCG1 expression and increased cleaved caspase-3 positive cells, indicating enhanced apoptosis when combinate with CAFs and 5-FU[1].
Axl-IN-21 (0.03-3 μM, 6 h) has strong Axl kinase inhibition in MDA-MB-231 breast cancer cells[2].
Axl-IN-21 (0.04-5 μM, 96-144 h) dose-dependently inhibits TGF-β1-induced Axl activation in MDA-MB-231 breast cancer cells[2].
Axl-IN-21 (0.04-5 μM, 24 h) inhibits the migrating process and invasiveness in MDA-MB-231 cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-231
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Concentration:0.03, 0.1, 0.3, 1 and 3 μM
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Incubation Time:6 h
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Result:Inhibited phosphorylation of Axl and downstream signaling (pAkt, pAxl).
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Cell Line:MDA-MB-231
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Concentration:0.04, 0.2, 1 and 5μM
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Incubation Time:96 to 144 h
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Result:Dose-dependently restored the protein levels of E cadherin and N-cadherin back to the control levels.
Reversed TGF β1-induced expression level changes of E-cadherin (an epithelial marker) and N-cadherin (a meschenchymal marker) EMT markers in MDA-MB-231 cells.
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Cell Line:MDA-MB-231
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Concentration:0.2, 1.0, 5.0 μM
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Incubation Time:24 h
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Result:Moderately inhibited the migrating process in MDA-MB-231 cells, suppressing the TGF β1 (10 ng/mL)-induced wound closure by ∼24.2%, ∼50.6%, and ∼58.4% at concentrations of 0.2, 1.0, and 5.0 μM.
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Cell Line:MDA-MB-231
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Concentration:0.04, 0.2, 1.0, or 5.0 μM
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Incubation Time:24 h
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Result:Inhibited cancer cell invasion by 48.5%, 52.1%, 73.5%, and 78.1% at concentration of 0.04, 0.2, 1.0, and 5.0 μM, respectively.
Axl-IN-21 (30, 90 mg/kg, p.o., daily for 21 days) in xenograft model of highly metastatic 4T1 murine breast cancer cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SNU668 cells (1×106) with or without induced CFAs (1×106, all cells in 100 μL PBS with 50% Matrigel)-BALB/c nude mice (5 weeks old)[1]
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Dosage:90 mg/kg
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Administration:p.o., daily for 3 weeks
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Result:Increased E-cadherin expression.
Significantly reduced tumor volume and weight when combined with 5-FU whereas either agent alone had only limited effects.
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Animal Model:SNU668 cells (1×106) with or without induced CFAs (1×106, all cells in 100 μL PBS with 50% Matrigel)-BALB/c nude mice (5 weeks old)[1]
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Dosage:90 mg/kg
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Administration:p.o., daily for 3 weeks
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Result:Increases E-cadherin expression.
Significantly reduced tumor volume and weight when combined with 5-FU whereas either agent alone had only limited effects.
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Animal Model:4T1 cells (0.5 × 106) induced-female BALB/c mice[2]
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Dosage:30 or 90 mg/kg
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Administration:p.o., daily for 21 days
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Result:Did not show an obvious effect on growth of the primary tumor.
Dose-dependently suppressed both size and number of liver metastases (21.3 and 13.0 in the 30 and 90 mg/kg dosing groups, respectively).
Chemical Information
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CAS No. 1958081-87-2
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Molecular Weight 542.56
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Formula C30H27FN4O5
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SMILES
COC1=CC2=C(N=CN=C2OC3=CC=C(C=C3F)NC(C4=C(N(C5=C(C4=O)C=C(C=C5)CC)C)C)=O)C=C1OC
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Kim TH, et al. Cancer-associated fibroblast-derived GAS6 increases resistance to chemotherapy through AXL/STAT3/ABCG1 in gastric cancer. Br J Cancer. 2025 Oct 28. doi: 10.1038/s41416-025-03218- [Content Brief]
[2]. Tan L, et al. 4-Oxo-1,4-dihydroquinoline-3-carboxamide Derivatives as New Axl Kinase Inhibitors. J Med Chem. 2016 Jul 28;59(14):6807-25. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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