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Chemical Structure| 2306178-56-1 Chemical Structure| 2306178-56-1

Structure of DMX-5804
CAS No.: 2306178-56-1

Chemical Structure| 2306178-56-1

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DMX-5804 is an effective, orally bioavailable, selective MAP4K4 inhibitor with an IC50 value of 3 nM for human MAP4K4 and a pIC50 value of 8.55, it has relatively weaker activity against MINK1/MAP4K6 (pIC50, 8.18) and TNIK/MAP4K7 (pIC50, 7.96).

Synonyms: DMX-5084

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Product Details of DMX-5804

CAS No. :2306178-56-1
Formula : C21H19N3O3
M.W : 361.39
SMILES Code : O=C1C2=C(N(C3=CC=CC=C3)C=C2C4=CC=C(OCCOC)C=C4)N=CN1
Synonyms :
DMX-5084
MDL No. :N/A

Safety of DMX-5804

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Related Pathways of DMX-5804

MAPK
Hippo

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
vascular smooth muscle cells (VSMCs) 10 μmol/L 24 hours Inhibition of MAP4K4 activity, restoration of VSMC contractility and morphological abnormalities Commun Biol. 2022 Oct 7;5(1):1071
Human cardiac microvascular endothelial cells (HCMECs) 5–15 μM 72 hours DMX-5804 significantly reduced SNO-Drp1, decreased Drp1 phosphorylation at Ser616, increased Drp1 phosphorylation at Ser637, and inhibited Drp1 translocation to mitochondria after HG/FFA treatment. Additionally, DMX-5804 ameliorated oxidative stress and ferroptosis induced by HG/FFA. Cardiovasc Diabetol. 2024 May 9;23(1):164
vCor.4U cardiomyocytes 10 μM 24 hours To evaluate the protective effect of DMX-5804 against oxidative stress-induced cell death, showing significant protection. Cell Stem Cell. 2019 Apr 4;24(4):579-591. e12
human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) 500 nM suppresses cell death from oxidative stress Basic Res Cardiol. 2021 May 20;116(1):34

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Myocardial ischemia-reperfusion injury model Oral 50 mg/kg Two doses, spaced 10 hours apart To validate the protective effect of DMX-5804 in vivo against myocardial ischemia-reperfusion injury, showing significant reduction in infarct size. Cell Stem Cell. 2019 Apr 4;24(4):579-591. e12
Mouse Myocardial infarction model Oral oral dosing Reduced infarct size Basic Res Cardiol. 2021 May 20;116(1):34
Mice VSMC-specific RhoA conditional knockout mice Intravenous injection 2.5 mg/kg Three times per week for 4 weeks Inhibition of MAP4K4 activity, reduction of AAA formation, restoration of vascular contractility and morphological abnormalities Commun Biol. 2022 Oct 7;5(1):1071
Mice Db/db mice Oral 3 mg/kg Three times per week for 24 weeks DMX-5804 significantly abrogated SNO-Drp1, suppressed Drp1 phosphorylation at Ser616, and inhibited the mitochondrial translocation of Drp1 in db/db mice. Furthermore, DMX-5804 improved cardiac microvascular perfusion, stimulated angiogenesis, enhanced endothelial barrier function, and suppressed endothelial-associated inflammation. Cardiovasc Diabetol. 2024 May 9;23(1):164

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.77mL

0.55mL

0.28mL

13.84mL

2.77mL

1.38mL

27.67mL

5.53mL

2.77mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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