INCB187175
INCB187175 is an orally active MRGPRX2 antagonist that blocks Gq signaling and β-arrestin recruitment. INCB187175 inhibits MRGPRX2-mediated mast cell degranulation and suppresses agonist-evoked vascular leakage in human MRGPRX2 knock-in mouse models without broadly inhibiting IgE-mediated mast cell activation. INCB187175 shows minimal inhibition of major cytochrome P450 (Cytochrome P450) isoforms and has a low hERG risk. INCB187175 can be used for research on mast cell-mediated diseases.
For research use only. We do not sell to patients.
- CAS No.: 3075832-16-2
- Formula: C23H21F7N6O2
- Molecular Weight:546.44
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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
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Biological Activity
Description
IC50 & Target
[1]|
MRGPRX2 |
β-arrestin 1.3 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| CHO-K1 | IC50 |
0.75 nM
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Antagonism of MRGPRX2 in CHO-K1 cells assessed by IP1 HTRF using Cortistatin-14 as agonist and IP1 accumulation as a measure of Gq signaling.
Antagonism of MRGPRX2 in CHO-K1 cells assessed by IP1 HTRF using Cortistatin-14 as agonist and IP1 accumulation as a measure of Gq signaling.
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acsmedchemlett.6c00376 |
| CHO-K1 | IC50 |
1.3 nM
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Inhibition of β-arrestin recruitment in CHO-K1 cells stably expressing ProLink-tagged MRGPRX2 and enzyme acceptor-tagged β-arrestin stimulated with Cortistatin-14.
Inhibition of β-arrestin recruitment in CHO-K1 cells stably expressing ProLink-tagged MRGPRX2 and enzyme acceptor-tagged β-arrestin stimulated with Cortistatin-14.
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acsmedchemlett.6c00376 |
| Mast cell | IC50 |
1.1 nM
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Inhibition of MRGPRX2-mediated β-hexosaminidase release in primary human mast cells differentiated from CD34+ progenitors stimulated with Cortistatin-14.
Inhibition of MRGPRX2-mediated β-hexosaminidase release in primary human mast cells differentiated from CD34+ progenitors stimulated with Cortistatin-14.
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acsmedchemlett.6c00376 |
In Vitro
INCB187175 inhibits MRGPRX2-mediated β-arrestin recruitment in CHO-K1 cells with an IC50 of 1.3 nM[1].
INCB187175 inhibits MRGPRX2-mediated degranulation in primary human mast cells with an IC50 of 1.1 nM[1].
The human liver microsomal CLH of INCB187175 is 0.6 L/h/kg[1].
INCB187175 has a Caco-2 Pm of 1.1 × 10−6 cm/s[1].
The free fraction of INCB187175 in human plasma is 2.5%[1].
INCB187175 shows minimal inhibition of CYP2D6 (> 25 μM) and major CYP subtypes (> 10 μM)[1].
INCB187175 inhibits hERG in patch-clamp experiments with an IC50 of 9.1 μM[1].
The FaSSIF solubility of INCB187175 is 452 μg/mL, and the SGF solubility is 250 μg/mL[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (transgenic human MRGPRX2 knock-in)[1]
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Dosage:2 mg/kg
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Administration:p.o.; single dose
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Result:Inhibited Cortistatin-14-induced Evans blue extravasation compared with vehicle at 2 mg/kg p.o.
PACAP 1-38 produced a numerical increase in Evans blue extravasation versus PBS; the PACAP 1-38 challenge response was interpreted cautiously.
IgE-mediated mast cell activation remained robust.
Chemical Information
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CAS No. 3075832-16-2
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Molecular Weight 546.44
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Formula C23H21F7N6O2
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SMILES
FC(C=C1)=CC=C1C2(CN(C(N[C@@H]3C[C@@H](O)C3)=O)C2)CNC4=CC(C(F)(F)F)=NC5=CC(C(F)(F)F)=NN54
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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)
INCB187175 Related Classifications
HY-190888 Related Classifications
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Keywords
- INCB187175
- 3075832-16-2
- INCB 187175
- INCB-187175
- Mas-related G-protein-coupled Receptor (MRGPR)
- Arrestin
- Cytochrome P450
- CYPs
- Gq signaling
- IgE-mediated mast cell activation
- MRGPRX2
- cytochrome P450
- hERG
- human MRGPRX2 knock-in mice
- mast cell degranulation
- mast cell-mediated diseases
- vascular leakage
- β-arrestin recruitment
- Inhibitor
- inhibitor
- inhibit