| Identification | Back Directory | [Name]
BAY-985 | [CAS]
2409479-29-2 | [Synonyms]
BAY-985
1-Propanone, 1-[4-[(1R)-1-[2-[[6-[6-(dimethylamino)-4-pyrimidinyl]-1H-benzimidazol-2-yl]amino]-4-pyridinyl]ethyl]-1-piperazinyl]-3,3,3-trifluoro- | [Molecular Formula]
C27H30F3N9O | [MDL Number]
MFCD32690108 | [MOL File]
2409479-29-2.mol | [Molecular Weight]
553.58 |
| Chemical Properties | Back Directory | [Boiling point ]
753.3±70.0 °C(Predicted) | [density ]
1.373±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: 50 mg/mL (90.32 mM) | [form ]
A solid | [pka]
10.06±0.10(Predicted) | [color ]
Light yellow to yellow | [InChIKey]
HZRJHVDNTDBTOZ-QGZVFWFLSA-N | [SMILES]
C(N1CCN([C@@H](C2C=CN=C(NC3NC4=CC(C5C=C(N(C)C)N=CN=5)=CC=C4N=3)C=2)C)CC1)(=O)CC(F)(F)F |
| Hazard Information | Back Directory | [Uses]
BAY-985 is a highly potent, orally active and selective ATP-competitive dual inhibitor of TBK1 and IKKε with IC50s of 2/30 and 2 nM for TBK1 (low/high ATP) and IKKε, respectively. Antitumor efficacy[1]. | [Biological Activity]
BAY-985 is a potent and highly selective TBK1/IKKε inhibitor. It is highly potent against TBK1 (IC50 = 2 nM, low ATP assay; 30 nM, high ATP assay) and IKKε (IC50 = 2 nM) and also in mechanocellular phosphorylation of interferon regulatory factor 3 (pIRF3) assays High potency (IC50 = 74 nM) and anti-proliferative effect on SK-MEL-2 cells (IC50 = 900 nM). | [in vitro]
BAY-985 inhibits FLT3, RSK4, DRAK1, and ULK1 with IC 50 s of 123, 276, 311, and 7930 nM, respectively.
BAY-985 inhibits the cellular phosphorylation of interferon regulatory factor 3 (IRF3) with an IC 50 of 74 nM.
BAY-985 is active in cellular mechanistic assay and shows anti-proliferative activity in a few cancer cells lines with IC 50 s of 900 and 7260 nM for SK-MEL2 (NRAS and TP53 mutated) and ACHN (CDKN2A mutated) cells, respectively. Cell Proliferation Assay | Cell Line: | ACHN and SK-MEL-2 cell lines | | Concentration: | | | Incubation Time: | td> 96 hours | | Result: | Inhibited proliferation i n SK-MEL2 and ACHN cells with IC 50 s of 900 and 7260 nM, respectively. | | [in vivo]
BAY-985 (200 mg/kg; po; bid; 111 days) results in weak antitumor efficacy.
BAY-985 shows high clearance (CL b = 4.0 L/h/kg, ca. 95% hepatic extraction), large volume of distribution at steady state (V ss =2.9 L/kg) and a short terminal half-life (t 1 /2 =0.79 h). | Animal Model: | Female NMRI nude mice bearing SK-MEL-2 human melanoma xenograft model | | Dosage: | 200 mg/kg | | Administration: | Applied po; twice daily (bid) continuously 111 days | | Result: | Treatment resulted in weak antitumor efficacy with a T/C tumor weight ratio of 0.6.
The treatment was well tolerated, with a maximum body weight loss of less than 10%. | | [target]
| Target | Value | TBK1
(in low ATP assay) | 2 nM | IKKε
(Cell-free assay) | 2 nM | < td style="border-bottom: 1px dotted #ccc;padding: 5px;"> TBK1
(in high ATP assay) 30 nM | pIRF3
(Cell-free assay) | 74 nM |
| [IC 50]
TBK1: 2 nM (IC50, low ATP); TBK1: 30 nM (IC50, high ATP); IKKε: 2 nM (IC50) | [References]
[1] Lefranc J, et al. Discovery of BAY-985, a Highly Selective TBK1/IKKε Inhibitor. J Med Chem. 2020 Jan 10. DOI:10.1021/acs.jmedchem.9b01460 |
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| Company Name: |
Twochem Co.Ltd
|
| Tel: |
021-021-58111628 15800915896 |
| Website: |
www.twochem.com |
|