Axl-IN-22
Axl-IN-22 is a selective, orally active dual inhibitor of AXL/MER, with IC50 values of 13 nM and 10 nM, respectively. Axl-IN-22 functionally inhibits AXL kinase activity, including ligand-independent autophosphorylation, and blocks the downstream PI3K/AKT signaling pathway, with excellent selectivity over TYRO3, IGF1R and INSR. Axl-IN-22 inhibits tumor growth in vivo and produces a synergistic effect when combined with anti-PD-1 antibody. Axl-IN-22 can be used in studies related to malignant tumors, leukemia, colon cancer and non-small cell lung cancer.
For research use only. We do not sell to patients.
- CAS No.: 2758062-71-2
- Formula: C34H35F2N9O3
- Molecular Weight:655.70
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
Axl 13 nM (IC50) |
Mer 10 nM (IC50) |
In Vitro
Axl-IN-22 (compound 4j) at 1 μM potently and selectively inhibits purified AXL and MER kinases, with IC50 values of 13 nM and 10 nM, respectively; it exhibits only extremely low activity against the remaining 364 human kinases[1].
Axl-IN-22 potently inhibits ligand-independent AXL autophosphorylation in MEF-AXL cells, with an IC50 of 4.1 nM[1].
Axl-IN-22 exhibits favorable metabolic stability in human liver microsomes, with a half-life of 184.9 min[1].
Axl-IN-22 (72 h) potently inhibits the proliferation of AXL- and MER-dependent Ba/F3 cells, with IC50 values of 37.5 nM and 50.9 nM, respectively. It exhibits moderate activity against FLT3-dependent cells, but shows only very low activity against TYRO3-, IGF1R-, INSR-dependent cells and parental Ba/F3 cells[1].
Axl-IN-22 (1.2-300 nM; 90 min) dose-dependently blocks the downstream PI3K/AKT signaling pathway in Ba/F3-TEL-AXL cells and inhibits the phosphorylation of AXL, Gab1 and AKT, with IC50 values of 18.3 nM, 27.9 nM and 19.4 nM, respectively[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Ba/F3-TEL-AXL cells
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Concentration:1.2, 3.7, 11, 33, 100 and 300 nM
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Incubation Time:90 min
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Result:Inhibited phosphorylation of AXL with an IC50 of 18.3 nM, phosphorylation of Gab1 with an IC50 of 27.9 nM, and phosphorylation of AKT with an IC50 of 19.4 nM in a dose-dependent manner.
Parmacokinetics
| Species | Dose | Route | T1/2 | C0 | AUClast | Vss | CL | Bioavailability | Cmax |
|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 1 mg/kg | i.v. | 4.23 h | 958 ng/mL | 4165 ng·h/mL | 1.27 L/kg | 3.93 mL/min/kg | 54.2 % | / |
| Rat[1] | 5 mg/kg | p.o. | 3.52 h | / | 11382 ng·h/mL | / | / | / | 894 ng/mL |
| Mice[1] | 1 mg/kg | i.v. | 1.12 h | 637 ng/mL | 541 | 1.9 L/kg | 30.7 mL/min/kg | 57.6 % | / |
| Mice[1] | 10 mg/kg | p.o. | 2.96 h | / | 2659 ng·h/mL | / | / | / | 691 ng/mL |
| Dog[1] | 1 mg/kg | i.v. | 6.7 h | 370 ng/mL | 1561 ng·h/mL | 3.92 L/kg | 10.2 mL/min/kg | 36.6 % | / |
| Dog[1] | 2 mg/kg | p.o. | 10.8 h | / | 1132 ng·h/mL | / | / | / | 166 ng/mL |
In Vivo
Axl-IN-22 (80 mg/kg; p.o.; twice daily; for 17 consecutive days) exhibits moderate monotherapy activity in colon cancer models. When combined with anti-PD-1 antibody, it achieves a 98% TGI, while enhancing anti-tumor immune cell infiltration and reducing immunosuppressive cell populations[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude mice were inoculated subcutaneously with 1 × 107 Ba/F3-TEL-AXL cells[1]
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Dosage:20 mg/kg; 60 mg/kg; 100 mg/kg
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Administration:p.o.; twice daily; 14 days
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Result:Significantly inhibited tumor growth compared to vehicle at all tested doses.
Achieved a tumor growth inhibition (TGI) rate of 71% at 100 mg/kg dose.
Reduced mean tumor volume to 641 mm3 on day 14 at 100 mg/kg dose (vs 1849 mm3 for vehicle).
Reduced mean tumor weight to 0.89 g at 100 mg/kg dose (vs 1.97 g for vehicle).
Caused no significant body weight loss across all dose levels.
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Animal Model:Male C57BL/6J mice were inoculated subcutaneously with 5 × 106 MC38 colon adenocarcinoma cells.[1]
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Dosage:80 mg/kg (monotherapy); 80 mg/kg (combination with anti-PD-1 antibody)
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Administration:p.o.; twice daily; 17 days (monotherapy); p.o.; twice daily; 17 days (combination with anti-PD-1 antibody, i.p.; twice weekly; 5 doses)
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Result:Achieved a 30% TGI rate as monotherapy (p > 0.05 vs vehicle).
Achieved a 98% TGI rate in combination with anti-PD-1 antibody, significantly outperforming the bemcentinib plus anti-PD-1 combination (63% TGI, p < 0.05).
Increased tumor-infiltrating CD3+ T cells to a mean 13.25% (p = 0.0318) compared to vehicle when combined with anti-PD-1 antibody.
Increased tumor-infiltrating CD8+ T cells to a mean 8.18% (p = 0.0016) compared to vehicle when combined with anti-PD-1 antibody.
Reduced immunosuppressive myeloid cell populations when combined with anti-PD-1 antibody.
Caused no added toxicity with the combination treatment.
Chemical Information
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CAS No. 2758062-71-2
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Molecular Weight 655.70
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Formula C34H35F2N9O3
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SMILES
CC(F)(C(N1CCC(CC1)C2=CC(C3=CC=C(C=C3F)NC(C4=C5CCCCN5N(C4=O)C6=NC=CC=C6)=O)=C7C(N)=NC=NN27)=O)C
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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
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Axl-IN-22 Related Classifications
HY-184433 Related Classifications
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