GFH018 methylbenzenesulfonate
GFH018 is an orally active, selective and ATP-competitive TGF-βR1 inhibitor with an IC50 of 40 nM. GFH018 reactivates the immune system by blocking the immunosuppression mediated by regulatory T cells and M2 macrophages. GFH018 inhibits tumor angiogenesis. GFH018 suppresses tumor growth in mouse tumor models. GFH018 can be used for the research of solid tumors, hepatocellular carcinoma, colorectal cancer, breast cancer, and relapsed/metastatic nasopharyngeal carcinoma.
For research use only. We do not sell to patients.
- CAS No.: 2345717-52-2
- Formula: C28H27N7O4S
- Molecular Weight:557.62
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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
Description
In Vitro
GFH018 (0.2 nM-40 μM; 40 min) methylbenzenesulfonate inhibits p38α enzymatic activity with an IC50 of 2,648 nM, and is 66.2-fold more selective for TGF-βR1 than for p38α[1].
GFH018 methylbenzenesulfonate inhibits the proliferation of NIH 3T3 fibroblasts with an IC50 of 0.73 μM[1].
GFH018 methylbenzenesulfonate inhibits TGF-β-induced Smad phosphorylation in HEK293 reporter cells, with an IC50 of 105 nM[1].
GFH018 (0.1-10 μM; 4 days) methylbenzenesulfonate dose-dependently inhibits TGF-β-induced Treg differentiation in a mouse CD4+ T cell-APC co-culture system, with the strongest inhibitory effect observed at the concentration of 10 μM[1].
GFH018 (0.1-10 μM; 16 h) methylbenzenesulfonate regulates cytokine secretion in human M2 macrophages in a dose-dependent manner, upregulating TNF-α and IL-6 levels while downregulating IL-10 levels at concentrations ranging from 0.1 to 10 μM[1].
GFH018 (0.1-10 μM; 6 h) methylbenzenesulfonate inhibits tube formation of HUVEC cells on Matrigel in a dose-dependent manner. After 6 h of incubation, significant reductions in the number of nodes and tube length are observed at concentrations ranging from 0.1 to 10 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
GFH018 (50 mg/kg; p.o.; twice daily) methylbenzenesulfonate and anti-PD-L1 antibody exerts synergistic antitumor efficacy in a mouse colorectal cancer model, with a TGI of 79.4%[1].
GFH018 (100 mg/kg; p.o.; twice daily; for 32 days) methylbenzenesulfonate potently inhibits the metastasis of breast cancer to multiple organs in vivo at an oral dose of 100 mg/kg twice daily[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 (female, 6-8 weeks old, subcutaneous inoculation of H22 murine hepatocellular carcinoma cells)[1]
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Dosage:15 mg/kg; 50 mg/kg
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Administration:p.o.; twice daily; 11 days
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Result:Induced tumor growth delay in a dose-dependent manner, with tumor growth inhibition (TGI) of 50.8% at 15 mg/kg and 57.5% at 50 mg/kg.
Sustained plasma exposure covering the in vitro p-Smad IC50 for approximately 3.5 h after the last 15 mg/kg dose and 5.5 h after the last 50 mg/kg dose.
Significantly reduced phosphorylated Smad3 protein levels in H22 tumors compared to vehicle control at 1 h post-final dose; inhibition was nearly absent at 12 h post-dose.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 2345717-52-2
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Molecular Weight 557.62
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Formula C28H27N7O4S
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SMILES
NC(/C=C/C1=C(C=CC2=NC=NN21)C3=C(CCC4)N4N=C3C5=CC=CC(C)=N5)=O.O=S(O)(C6=CC=C(C=C6)C)=O
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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)
GFH018 methylbenzenesulfonate Related Classifications
HY-160215A Related Classifications
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