DT-9081
DT-9081 is an orally active and selective EP4 receptor antagonist, IC50 = 2.49 nM. DT-9081 blocks PGE2/EP4R-mediated cAMP signaling, counteracts EP4R-driven immunosuppression, and restores antitumor immunity. DT-9081 combined with anti-PD-1 antibody significantly improves tumor growth inhibition and animal survival in mouse tumor models. DT-9081 can be used in cancer-related research.
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- No. CAS: 2639645-80-8
- Fòrmula: C25H29F3N2O4
- Peso molecular:478.50
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Descripciòn
IC50 & Target
[1]|
EP4 2.49 nM (IC50) |
CYP2C8 11.7 μM (IC50) |
CYP2C19 3.17 μM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK293 | IC50 |
2.49 nM
|
Antagonism of human EP4 receptor in HEK-293 cells assessed by EPAC BRET cAMP assay with Prolume Purple luciferase substrate and 20 min BRET recording after EC80 TCS2510 stimulation.
Antagonism of human EP4 receptor in HEK-293 cells assessed by EPAC BRET cAMP assay with Prolume Purple luciferase substrate and 20 min BRET recording after EC80 TCS2510 stimulation.
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acs.jmedchem.6c00863 |
| HEK293 | IC50 |
3.68 nM
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Antagonism of mouse EP4 receptor in HEK-293 cells assessed by EPAC BRET cAMP assay with Prolume Purple luciferase substrate and 20 min BRET recording after EC80 TCS2510 stimulation.
Antagonism of mouse EP4 receptor in HEK-293 cells assessed by EPAC BRET cAMP assay with Prolume Purple luciferase substrate and 20 min BRET recording after EC80 TCS2510 stimulation.
|
acs.jmedchem.6c00863 |
| HEK293 | IC50 |
7.00 nM
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Antagonism of rat EP4 receptor in HEK-293 cells assessed by EPAC BRET cAMP assay with Prolume Purple luciferase substrate and 20 min BRET recording after EC80 TCS2510 stimulation.
Antagonism of rat EP4 receptor in HEK-293 cells assessed by EPAC BRET cAMP assay with Prolume Purple luciferase substrate and 20 min BRET recording after EC80 TCS2510 stimulation.
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acs.jmedchem.6c00863 |
| HEK293 | IC50 |
21.46 nM
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Antagonism of dog EP4 receptor in HEK-293 cells assessed by EPAC BRET cAMP assay with Prolume Purple luciferase substrate and 20 min BRET recording after EC80 TCS2510 stimulation.
Antagonism of dog EP4 receptor in HEK-293 cells assessed by EPAC BRET cAMP assay with Prolume Purple luciferase substrate and 20 min BRET recording after EC80 TCS2510 stimulation.
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acs.jmedchem.6c00863 |
In Vitro
DT-9081 (compound 10m) is a potent antagonist of human EP4R in the human HEK-293 EPAC BRET cAMP assay, with an IC50 of 2.49 nM, and maintains nanomolar potency against mouse, rat, and dog EP4R; it blocks EP4R/cAMP signaling in human IL-2-activated T cells, with an IC50 of 65 nM[1].
DT-9081 binds EP4R with an inhibition rate of 100.1% and is highly selective for other prostanoid receptors[1].
DT-9081 (10 μM) shows no significant off-target activity in the Safety Screen 87 panel, except for 62% binding inhibition of 5-HT2B, and has no functional 5-HT2B activity[1].
DT-9081 exhibits acceptable cross-species in vitro stability, a high plasma protein binding rate, and inhibits CYP2C8/2C19 and OATP1B1/1B3/BCRP[1].
DT-9081 (30 μM) weakly inhibits hERG in stably transfected CHO cells, with an inhibition rate of 16.7%[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
| Species | Dose | Route | CL | Vdss | T1/2 | Tmax | Cmax | AUClast | F |
|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 2 mg/kg | i.v. | 0.2 L/h/kg | 0.4 L/kg | 1.5 h | / | / | / | / |
| Mice[1] | 30 mg/kg | p.o. | / | / | / | 0.4 h | 19032 ng/mL | 65375 ng·h/mL | 44 % |
| Mice[1] | 10 mg/kg | p.o. | / | / | / | / | 4591 ng/mL | 25204 ng·h/mL | 51 % |
| Rat[1] | 2 mg/kg | i.v. | 0.05 L/h/kg | 0.4 L/kg | 4.7 h | / | / | / | / |
| Rat[1] | 10 mg/kg | p.o. | / | / | / | 4.0 h | 11897 ng/mL | 158721 ng·h/mL | 85 % |
| Dog[1] | 1 mg/kg | i.v. | 0.005 L/h/kg | 0.12 L/kg | 16.5 h | / | / | / | / |
| Dog[1] | 3 mg/kg | p.o. | / | / | / | 0.5 h | 23016 ng/mL | 287261 ng·h/mL | 74 % |
In Vivo
DT-9081 (30 mg/kg; p.o.; twice daily; day 8 to day 28) shows low single-agent activity in the 4T1 triple-negative breast cancer model, but when combined with anti-PD-1 and Cisplatin (HY-17394), it increases the response rate[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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No. CAS 2639645-80-8
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Peso molecular 478.50
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Fòrmula C25H29F3N2O4
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SMILES
O=C(O)C1=CC=C([C@@H](NC(CC(C)(N2C[C@H](OC3=CC=CC(C(F)(F)F)=C3)CC2)C)=O)C)C=C1
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
DT-9081 Related Classifications
HY-189816 Related Classifications
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