445430-58-0
BMS-345541 free base
CAS: 445430-58-0
Molecular Formula: C14H17N5
445430-58-0 - Names and Identifiers
445430-58-0 - Physico-chemical Properties
| Molecular Formula | C14H17N5 |
| Molar Mass | 255.32 |
| Density | 1.32±0.1 g/cm3(Predicted) |
| Boling Point | 449.5±45.0 °C(Predicted) |
| pKa | 9.02±0.10(Predicted) |
| Storage Condition | under inert gas (nitrogen or Argon) at 2–8 °C |
| Use | BMS-345541 is a selective IKK catalytic subunit IKK-1 and IKK-2 inhibitor, inhibiting IKK-2 and IKK-1 with IC50 values of 0.3 μM and 4 μM respectively. BMS-345541 binds to the allosteric site of IKK. |
| In vitro study | In THP-1 monocytes, BMS-345541 dose-dependently inhibited TNF-α-stimulated phosphorylation of IκBα with an IC 50 of 4 μm. BMS-345541 inhibited lipopolysaccharide-stimulated tumor necrosis factor, interleukin-1β, interleukin-8 and interleukin-6 in THP-1 cells with IC 50 values in the range of 1 to 5 μm. BMS-345541 binds in a mutually exclusive manner to a polypeptide inhibitor that is identical to the amino acid sequence of IκBα 26-42 except for serine -32 and serine -32 is changed to aspartic acid. BMS-345541 bind ADP in a non-mutually exclusive manner. BMS-345541 bind to allosteric sites of IKK-1 and IKK-2, thereby affecting different active sites of the subunits. BMS-345541 affects several mitotic cell cycle transitions, including entry into mitosis, early-metaphase to late progression, and cytokinesis. Addition of BMS-345541 to the cells caused the cells to stay in G-phase and hindered the activation of Aurora A,B and C, the activation of Cdk1 and the phosphorylation of histone H3. BMS-345541 treatment of mitotic cells results in the degradation of precocious cyclins B1 and securin, defective chromosome segregation and improper cytoplasmic division. BMS-345541 also found that the spindle checkpoint was covered in the arrested cells of thiamidazole. These effects are not primarily due to BMS-345541 direct inhibition of mitotic kinases such as Cdk1,Aurora A or B,Plk1 or nek2. BMS-345541(10 μm) inhibited the growth of normal human epidermal melanocytes and metastatic melanoma cells (SK-MEL-5,A375, and HS294T) by 96% and 99% at 72 hours, respectively. BMS-345541 treatment of SK-MEL-5 cells by caspase-dependent and AIF-dependent mitochondrial-mediated means resulted in 87% apoptotic cells at 24 hours. BMS-345541(10 μm) resulted in a 76% decrease in IKK activity, a 95% decrease in NF-kB activity, and CXCL1 production. BMS-345541 suppress the growth of T-cell acute lymphoblastic leukemia (T-ALL), cell lines include BE-13,RPMI-8402 -13, and DND-41, all of which contain mutations in notch1. BMS-345541 also inhibits the growth of primary T-ALL cells in pediatric patients with an IC50 of 2-6 microns. In BE-13 and DND-41 cells, BMS-345541(5 μm) induced cell arrest in the G2 / M phase of the cell cycle and prevented RPMI-8402 cells from staying in the sub-g1 phase. Treatment with 5 μmbms-345541 for 16 H resulted in an increase in apoptotic cells accompanied by time-dependent procaspase-8, procaspase-3, and poly (ADP-ribose) dissociation. BMS-34554(5 μm) induced time-dependent dephosphorylation of IκBα and p65. BMS-34554 treatment of T-ALL cells results in nuclear translocation of FOXO3a, including control of p21. In Human Umbilical vein endothelial cells, BMS-345541 inhibition of TNFα-induced expression of ICAM-1 and VCAM-1, IC 50 was 5 μm. |
| In vivo study | BMS-345541 effectively inhibited the growth of melanoma tumors in a dose-dependent manner. The tumor mice treated with 75 mg/kg BMS-345541 showed effective inhibition of the growth of SK-MEL-5,A375 and Hs 294T, with inhibition rates of 86%,69% and 67% respectively compared with the control group. BMS-345541 weight ratio, clinical bowel score, mean injury score, and mean inflammation score in mice with dextran sulfate sodium-induced colitis reduced at an oral dose of 100 mg/k, 0.86(vs control group 0.77),1.0(vs control group 2.5),5.66(vs control group 8.52),6.82(vs control group 12.33). BMS-345541(100 mg/kg), orally administered by gavage at the time of type I collagen immunization, suppressed the clinical symptoms of the CIA mouse model with a decrease in paw swelling. BMS-345541(100 mg/kg) reduced the cumulative arthritic injury score from 4.4 to 0 with low-grade degradation and inflammation of the tibiotarsal joint, synovial hyperplasia, severity of bone resorption and cartilage erosion. There was no apparent damage in the joints of the animals, which was no difference in the histological phenotype observed from those from age-matched, disease-free control animals. BMS-345541 dose-dependently inhibited IL-1β signaling, with the 100 mg/kg dose group of animals showing levels consistent with disease-free control animals. |
445430-58-0 - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 3.917 ml | 19.583 ml | 39.167 ml |
| 5 mM | 0.783 ml | 3.917 ml | 7.833 ml |
| 10 mM | 0.392 ml | 1.958 ml | 3.917 ml |
| 5 mM | 0.078 ml | 0.392 ml | 0.783 ml |
Last Update：2024-01-02 23:10:35
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Product Name: BMS-345541 free base Visit Supplier Webpage Request for quotationCAS: 445430-58-0
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Mobile: 18021002903
QQ: 3008007409
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