|
|
| | BAY-985 Basic information |
| Product Name: | BAY-985 | | 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-;BAY-985,IKK,BAY985,IκB kinase,melanoma,IKKε,TBK1,inhibit,I kappa B kinase,Inhibitor,BAY 985,antitumor;(R)-1-(4-(1-(2-((6-(6-(Dimethylamino)pyrimidin-4-yl)-1H-benzo[d]imidazol-2-yl)amino)pyridin-4-yl)ethyl)piperazin-1-yl)-3,3,3-trifluoropropan-1-one | | CAS: | 2409479-29-2 | | MF: | C27H30F3N9O | | MW: | 553.58 | | EINECS: | | | Product Categories: | | | Mol File: | 2409479-29-2.mol |  |
| | BAY-985 Chemical Properties |
| 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) |
| | BAY-985 Usage And Synthesis |
| 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 |
|
| | BAY-985 Preparation Products And Raw materials |
|