DMX-5804

SKU: orb1301753

Description

DMX-5804 is a highly potent and selective MAP4K4 inhibitor exhibiting an IC50 of 3 nM. This compound has been shown to promote cardiomyocyte survival in vitro and demonstrates cardioprotective effects by mitigating ischemia-reperfusion injury in murine models.

Research Area

Signal Transduction

Key Properties

• CAS Number: 2306178-56-1
• MW: 361.39
• Purity: 99.63% (May vary between batches)
• Formula: C₂₁H₁₉N₃O₃
• SMILES: COCCOc1ccc(cc1)-c1cn(-c2ccccc2)c2nc[nH]c(=O)c12
• Target: MAPK
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (11.07 mM);DMSO:125 mg/mL (345.89 mM)

Bioactivity

• Target IC50:
  MLK1/MAP3K9:7.19 (pIC50)|Abl-1:5.80 (pIC50)|KHS/MAP4K5:6.36 (pIC50)|VEGFR:5.72 (pIC50)|NUAK:6.88 (pIC50)|Aurora B:5.49 (pIC50)|FLT3:5.31 (pIC50)|TNIK/MAP4K7:7.96 (pIC50)|GSK-3β:4.66 (pIC50)|MLK3/MAP3K11:6.99 (pIC50)|GLK/MAP4K3:4.95 (pIC50)|MAP4K4:3 nM|MAP4K4:8.55 (pIC50)|MINK1/MAP4K6:8.18 (pIC50)|GCK/MAP4K2:6.50 (pIC50)
• In Vivo:
  DMX-5804 reduces ischemia-reperfusion injury in mice by more than 50%.
• In Vitro:
  DMX-5804, that rescues cell survival, mitochondrial function.
• Cell Research:
  Mitochondrial function in hiPSC-CMs was determined using a Seahorse XFe24 Analyzer. vCor.4U cells (60,000/well) were transferred to 0.1% gelatin-coated XF24 plates and maintained for 5 d. On day 6, DMX-5804 was added 45 min prior to challenge with menadione for 2 h. The medium was replaced 1 hr before the assay, using bicarbonate-free Seahorse assay medium (8.3 g L-1 DMEM Base , 10 mM glucose, 2 mM L-alanyl-L-glutamine dipeptide, 1 mM sodium pyruvate , pH 7.4). Cells were maintained at 37 C without supplemental CO2 starting 1 hr before the assay. For each state measured, three assay cycles were performed (4 min mixing, 2 min wait, and 2 min measurement periods, with readings every 15 s). The basal oxygen consumption rate (OCR) and extracellular acidification rate were determined, followed by sequential injection of 1 μM oligomycin A to inhibit ATP synthase, 0.5 μM carbonyl cyanide-4-phenylhydrazone to uncouple oxidative phosphorylation, and 1 μM antimycin A/rotenone to inhibit mitochondrial complex III and I. For each condition, 12 wells were tested, comprising 4 independent experiments.
• Animal Research:
  n vivo pharmacokinetic profiling was performed in female CD-1 mice, using 3 animals per time point. First, 30% w/v Kleptose as excipient was dissolved in water and vortexed gently for several min. Next, 30 mg of DMX-5084 was dissolved into 0.6 mL of DMSO, for a concentration of 50 mg ml-1, and 4.5 mL of the Kleptose solution was added to 0.5 mL of the test compound solution. A precipitate forms, which re-dissolves over 2-5 min, leaving a clear or slightly hazy solution with a final concentration of 5 mg/ml. The dosing solution is used as soon as practicable, vortexing immediately prior to use. This amount was sufficient formulation for 25 doses of 200 μL (20 g mouse). Compounds were administered orally at 50 mg/kg, with terminal blood (plasma) sampling at 10 min, 30 min, 1 h, 2.5 h, 5 h, 10 h, and 20 h.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

MAPK Kinase Kinase Kinase, MAP4K, MAP4K4, MAP4K6, Inhibitor, inhibit, MINK1, DMX 5084, DMX 5804, DMX5084, DMX-5084, DMX5804, DMX-5804

Compound Identifiers

PubChem CID

137334091