MK-1088
MK-1088 is an orally active A2A/A2B adenosine receptor antagonist with human A2A Ki of 0.31 nM, human A2B Ki 5.3 nM. MK-1088 blocks receptor downstream signaling, inhibits CREB phosphorylation and reverses adenosine-mediated immunosuppression. MK-1088 restores TNF−α release and enhances tumor immune surveillance. MK-1088 can be used for the research of cancer[1].
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- CAS No.: 2433765-51-4
- Formule: C23H29FN8O2
- Masse moléculaire:468.53
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
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Activité biologique
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hA2AAR 0.31 nM (Ki) |
hA2B 5.3 nM (Ki) |
hA1AR 82 nM (Ki) |
hA3 233 nM (Ki) |
MK-1088 (Compound 46) (60 min at room temperature) potently binds to hA2AR expressed in CHO cell membranes with a Ki of 0.31 nM[1].
MK-1088 (60 min at room temperature) binds to hA2BR with a Ki of 5.3 nM, showing a 16-fold lower potency relative to hA2BR[1].
MK-1088 (60 min at room temperature) binds to hA1R expressed in CHO-K1 cell membranes with a Ki of 82 nM, showing 259-fold lower potency relative to hA2AR[1].
MK-1088 (0.1 nM-100 μM) dose-dependently inhibits NECA-stimulated CREB phosphorylation in human CD4+ T cells with an IC50 of 70 nM[1].
MK-1088 dose-dependently recovers LPS (HY-D1056)-stimulated, NECA (HY-103173)-suppressed TNF-α release in human whole blood[1].
MK-1088 has a clean off-target profile for cardiac ion channels and most CYP enzymes, with only moderate inhibition of CYP3A4-midazolam (IC50 = 4.1 μM) and no time-dependent CYP3A4 inhibition[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | CLunbound | Vd | T1/2 | Bioavailability |
|---|---|---|---|---|---|---|
| Rat[1] | 0.5 mg/kg | i.v. | 45.4 mL/min/kg | 9.3 L/kg | 2.3 h | / |
| Rat[1] | 3 mg/kg | p.o. | / | / | / | 36.8 % |
| Dog[1] | 0.1 mg/kg | i.v. | 6.6 mL/min/kg | 5.7 L/kg | 9.2 h | / |
| Dog[1] | 3 mg/kg | p.o. | / | / | / | 42.4 % |
| Rhesus monkey[1] | 0.5 mg/kg | i.v. | 45.2 mL/min/kg | 8.9 L/kg | 2.2 h | / |
| Rhesus monkey[1] | 3 mg/kg | p.o. | / | / | / | 51.4 % |
MK-1088 (30 mg/kg; p.o.; twice daily; 21 days) delivers 47% tumor growth inhibition as a single agent in mice bearing CM3 syngeneic tumors[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 mice (syngeneic tumor model)[1]
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Dosage:30 mg/kg
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Administration:p.o.; twice daily; 16 days
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Result:Achieved 54% tumor growth inhibition (TGI) relative to control tumors at day 16, p < 0.0001 by one-way ANOVA.
Reached 97% A2AR target engagement based on mouse A2AR affinity (Ki = 6 nM) and 10 h unbound plasma exposure.
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Animal Model:Mice (10 animals per group; syngeneic tumor model)[1]
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Dosage:30 mg/kg
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Administration:p.o.; twice daily; 21 days
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Result:Afforded 47% tumor growth inhibition (TGI) as a single agent on study day 14.
Chemical Information
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CAS No. 2433765-51-4
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Masse moléculaire 468.53
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Formule C23H29FN8O2
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SMILES
NC1=NC2=C(C=C(C(OC)=C2)F)C3=NC([C@@H]4CC[C@@H](N(C4)C5=CN(N=C5)CC(O)(C)C)C)=NN31
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
MK-1088 Related Classifications
HY-183599 Related Classifications
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