Autotaxin-IN-8
Autotaxin-IN-8 (Compound 14E) is an orally active Autotaxin inhibitor with an IC50 of 14.2 nM against hAutotaxin. Autotaxin-IN-8 inhibits Autotaxin activity, MAPK activation, LPAR1 and p-ERK1/2. Autotaxin-IN-8 reduces the phosphorylation levels of JNK and p38. Autotaxin-IN-8 decreases collagen deposition in a mouse model of pulmonary fibrosis. Autotaxin-IN-8 can be used in research related to pulmonary fibrosis.
For research use only. We do not sell to patients.
- CAS No.: 3058084-21-9
- Formula: C21H20ClN9O
- Molecular Weight:449.90
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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]|
ERK1 |
ERK2 |
LPA1 Receptor |
Autotaxin 14.2 nM (IC50) |
In Vitro
Autotaxin-IN-8 (14.2 nM; 2 h) potently inhibits recombinant human ATX enzymatic activity with an in vitro IC50 of 14.2 nM[1].
Autotaxin-IN-8 (94.31 μM; 24 h) shows low cytotoxicity toward human normal lung epithelial L132 cells with an IC50 of 94.31 μM[1].
Autotaxin-IN-8 (1 μM; 12 h) significantly inhibits basal, TGF-β-stimulated, and LPC-stimulated migration of A549 cells over 12 h[1].
Autotaxin-IN-8 (1 μM; 48 h) significantly reduces spontaneous, TGF-β-triggered, and LPC-triggered collagen gel contraction by MLg cells over 48 h[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Human normal lung epithelial L132 cells
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Concentration:0.1-5.0 μM (concentration-dependent study); 0.5 μM (time-dependent study); 0.5 μM (LPC/LPA co-treatment pre-incubation); 0.5 μM (TGF-β co-treatment pre-incubation)
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Incubation Time:75 min (concentration-dependent study); 30-75 min (time-dependent study); 75 min pre-incubation + 15 min LPC/LPA stimulation (co-treatment); 3 h pre-incubation + 3 h TGF-β stimulation (co-treatment)
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Result:Inhibited phosphorylation of p-JNK with an EC50 of 0.958 μM, p-p38 with an EC50 of 0.785 μM, and p-ERK1/2 with an EC50 of 0.297 μM, with marked inhibition at concentrations as low as 0.5 μM.
Inhibited phosphorylation of p-JNK with an estimated time of 35.4 min, p-p38 with an estimated time of 39.13 min, and p-ERK1/2 with an estimated time of 30.46 min, with effects observed within 30 min.
Suppressed LPC-induced activation of p-JNK, p-p38, and p-ERK1/2 but had no effect on LPA-induced activation.
Significantly reduced TGF-β-induced phosphorylation of JNK, ERK, and p38.
Parmacokinetics
| Species | Dose | Route | Tmax | Cmax | T1/2 | AUC0-last |
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| Rat[1] | 1 mg/kg | p.o. | 2.67 h | 135.26 ng/mL | 5.49 h | 631.01 |
In Vivo
Autotaxin-IN-8 (1-3 mg/kg; p.o.; daily; 21 days) reduces collagen deposition, fibrosis marker expression, and inflammation in a Bleomycin (HY-17565A)-induced pulmonary fibrosis mouse model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (male, 8 weeks old, bleomycin-induced pulmonary fibrosis)[1]
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Dosage:1 mg/kg; 3 mg/kg
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Administration:p.o.; daily; 21 days
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Result:Markedly reduced bleomycin-induced collagen deposition in lung tissue.
Decreased lung tissue expression of α-SMA and TGF-β.
Suppressed the bleomycin-induced increase in LPAR1 and p-ERK1/2.
Mitigated bleomycin-provoked inflammatory responses by reducing IL-1β and IL-6 expression in lung tissue.
Chemical Information
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CAS No. 3058084-21-9
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Molecular Weight 449.90
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Formula C21H20ClN9O
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SMILES
ClC1=CC=C(C=C1)CCNC2=NC=C(C3=NN=C(N4C[C@@]5([H])[C@H](C6=CN=NN6)[C@@]5([H])C4)O3)C=N2
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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)
Autotaxin-IN-8 Related Classifications
HY-181931 Related Classifications
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