| Bioactivity | BRD6989, an analog of the natural product cortistatin A (dCA), inhibits CDK8 and upregulates IL-10. BRD6989 selectively binds a complex of CDK8 with an IC50 of ~200 nM. BRD6989 inhibits the kinase activity of recombinant CDK8 or CDK19 complexes[1]. | ||||||||||||
| Invitro | Pretreatment of BMDCs with BRD6989 (0-100 μM; for 48 hours) increases IL-10 production with an EC50 of ~1 μM[1]. BRD6989 (0.6, 1.7, 5, 15 μM) suppresses phosphorylation of the STAT1 transactivation domain at Ser727 in IFNγ-stimulated BMDCs[1]. BRD6989 (5 µM; ~2 hours) suppresses induction of STAT1–STAT2 activity and NF-κB activation to a varying degree after stimulation of BMDMs[1]. BRD6989 (5 µM; 24 hours) enhances IL-10 production in activated human and murine macrophages and dendritic cells[1]. | ||||||||||||
| Name | BRD6989 | ||||||||||||
| CAS | 642008-81-9 | ||||||||||||
| Formula | C16H16N4 | ||||||||||||
| Molar Mass | 264.33 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Johannessen L, et al. Small-molecule studies identify CDK8 as a regulator of IL-10 in myeloid cells. Nat Chem Biol. 2017 Oct;13(10):1102-1108 |