DA29
DA29 is a human caseinolytic protease P (hClpP) activator, with an EC50 of 0.85 μM and a Kd of 185 nM. DA29 binds to the hydrophobic allosteric pocket of this enzyme, activates its proteolytic function, and displaces hClpX from the hClpXP complex. DA29 induces mitochondrial dysfunction and ROS accumulation. DA29 exerts cytotoxic effects on cancer cells and organoids. DA29 can be used in the research of diffuse intrinsic pontine glioma.
For research use only. We do not sell to patients.
- Formula: C20H18F6N2O
- Molecular Weight:416.36
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
DA29 (compound 26) potently activates purified human hClpP, with an EC50 of 0.85 μM and an activation rate of 95% at a concentration of 100 μM in cell-free fluorescence assays; it binds to purified human hClpP with a Kd of 185 nM; and it enhances the thermal stability of hClpP in Caco-2 cells[1].
DA29 exhibits high basolateral permeability in Caco-2 and MDCK-MDR1 cell monolayer models, with BA/AB ratios of 5.91 and 4.61, respectively, suggesting its potential blood-brain barrier penetration ability; meanwhile, it shows weak interaction with P-gp (EC50 = 71 μM)[1].
DA29 (1-100 μM; 72 h) exhibits cytotoxic activity against the SU-DIPG-36 and SU-DIPG-50 diffuse intrinsic pontine glioma (DIPG) cell lines, with IC50 values of 4.0 μM and 11.6 μM, respectively; it reduces the viability of DIPG tumor organoids DMG2_O and DMG3_O, with IC50 values of 2.57 μM and 1.94 μM, respectively[1].
DA29 (1 μM; 1-24 h) significantly raises intracellular ROS levels in SU-DIPG-36 cells, with the notable increase detected at 6 h[1].
DA29 (1.5 μM; 24 h) displaces ClpX from the ClpXP complex, reduces the levels of specific mitochondrial respiratory chain subunits and TFAM, and decreases mtDNA levels in SU-DIPG-36 cells; it also reduces the levels of mitochondrial ribosomal subunits, inhibits polyribosome formation, and disassembles the ClpXP complex[1].
DA29 (24 h) remodels the lipid profiles of SU-DIPG-36 and SH-SY5Y cells, reduces most lysophosphatidylcholine (LPC) and sphingomyelin (SM) species, and alters the species distribution of triglyceride (TG), which is consistent with the characteristics of impaired mitochondrial function[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:SU-DIPG-36 DIPG cell line
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Concentration:1.5 μM
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Incubation Time:24 h
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Result:Completely abolished ClpX levels while leaving ClpP unaffected, indicating ClpXP complex disassembly.
Reduced levels of SDHB (Complex II), UQCRC2 (Complex III), ATP5A (Complex V), and COI (Complex IV), but not NDUFB8 (Complex I).
Strongly reduced TFAM levels and dramatically decreased mtDNA levels.
Left VDAC1 (mitochondrial mass marker) unchanged.
Chemical Information
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Molecular Weight 416.36
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Formula C20H18F6N2O
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SMILES
O=C1N(CC2=CC=C(C(F)(F)F)C=C2)CCN(CC3=CC=CC(C(F)(F)F)=C3)C1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)