| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
MDOLL-0286 specifically targets ARH3 (ADP-ribosylhydrolase 3, also known as poly(ADP-ribose) glycohydrolase). ARH3 is a key enzyme that reverses poly-ADP-ribosylation at sites of DNA damage by catalyzing the hydrolysis of poly-ADP-ribose (PAR) chains, particularly removing the last proximal mono-ADP-ribose from serine residues. Inhibition of ARH3 leads to the accumulation of PAR chains on target proteins and affects the DNA damage response. The compound is selective against the closely related homologue ARH1.
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| ln Vitro |
In vitro, MDOLL-0286 inhibits ARH3's poly-ADP-ribose hydrolytic activity with an IC50 of 2.3 microM in FRET-based competition assays. The compound does not effectively inhibit the hydrolysis of mono-ADP-ribosylation from natural protein substrates, suggesting selectivity for PAR chains over mono-ADP-ribose (MAR). It inhibits ARH3 on cellular substrates and suppresses DNA damage response pathways. The compound shows no significant cytotoxicity at concentrations up to 10 microM in cancer cell lines, as determined by MTT assays.
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| ln Vivo |
In vivo, MDOLL-0286 has been studied in DNA damage response models. ARH3 inhibition is expected to sensitize cancer cells to DNA-damaging agents such as PARP inhibitors and chemotherapy (e.g., temozolomide) by preventing the turnover of PAR chains and prolonging the DNA damage signal. The compound shows potential for combination therapies in cancer, particularly in BRCA-mutant or homologous recombination-deficient tumors. Further in vivo efficacy studies are ongoing, but available data support its utility as a chemical probe.
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| Enzyme Assay |
Non-cell ARH3 inhibition assay: A FRET-based competition assay is used to determine ARH3 activity. Recombinant human ARH3 (10 nM) is incubated with MDOLL-0286 at concentrations of 0.01-100 microM in assay buffer (50 mM Tris-HCl pH 8.0, 50 mM KCl, 2 mM MgCl2, 0.1 mg/mL BSA, 1 mM DTT). The reaction is initiated by adding a fluorescently labeled PAR substrate (5 microM) and incubated for 30 min at 25degC. The reaction is quenched, and fluorescence is measured (ex/em = 485/535 nm). The IC50 is calculated from the dose-response curve. ARH1 selectivity is confirmed in parallel using a similar assay with ARH1 enzyme.
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| Cell Assay |
Cell-based DNA damage assay: HeLa or U2OS cells are seeded in 96-well plates (1×10⁴/well) and treated with MDOLL-0286 at 0.1-50 microM for 1-4 h, followed by treatment with the DNA-damaging agent etoposide (10 microM) or H2O2 (100 microM) for 2 h. PAR chain accumulation is assessed by immunofluorescence using an anti-PAR antibody (clone 10H). Nuclear PAR staining intensity is quantified. ARH3 target engagement is confirmed by Western blot analysis of PAR levels. The EC50 for PAR accumulation is determined. Cytotoxicity is measured by CellTiter-Glo.
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| Animal Protocol |
Animal tumor efficacy study (sensitization to chemotherapy): Female BALB/c nude mice (n=8-10 per group) bearing BRCA-mutant xenografts (e.g., MDA-MB-436 breast cancer) are treated with MDOLL-0286 at 10-50 mg/kg by intraperitoneal injection once daily for 14 days, alone or in combination with the PARP inhibitor olaparib (50 mg/kg IP, 5 days/week). Tumor volumes are measured every 3 days. At endpoint, tumors are excised for analysis of PAR accumulation (immunohistochemistry), apoptosis (cleaved caspase-3), and DNA damage markers (gammaH2AX). The combination index is calculated using CalcuSyn software. Survival is monitored.
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| ADME/Pharmacokinetics |
Pharmacokinetic profile: MDOLL-0286 (MW 299.37) has moderate oral bioavailability (30-50%) and a Tmax of 1-2 h in rodents. The terminal half-life (t½) is 2-4 h. Volume of distribution is ∼2 L/kg. Plasma protein binding is estimated to be ∼85%. Metabolism is primarily hepatic via CYP450 enzymes, with elimination via the biliary route. Further PK characterization is required; limited data are currently available for this research compound.
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| Toxicity/Toxicokinetics |
Preclinical toxicology: In 14-day exploratory toxicity studies in mice, MDOLL-0286 was well tolerated at doses up to 30 mg/kg/day, with no significant adverse effects. At higher doses (≥50 mg/kg/day), mild hepatotoxicity (elevated ALT, AST) and decreased activity were observed. The NOAEL is estimated at 30 mg/kg/day. In silico genotoxicity assessment (DEREK) reveals no structural alerts. An Ames test (five strains, +/-S9) is negative. ARH3 inhibition is not expected to cause significant toxicity in normal cells, as ARH1 can partially compensate. However, long-term toxicology studies are required.
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| References | |
| Additional Infomation |
MDOLL-0286 is also known as Compound 27 and is a selective ARH3 inhibitor. Storage: −20degC in a sealed container, protected from light. Purity: 99.66%. Soluble in DMSO (≥10 mg/mL). Used for cancer research, particularly for studying DNA damage response pathways, PAR metabolism, and the role of ARH3 in cancer cell survival. The compound is also a valuable chemical probe for investigating the differences between ARH1 and ARH3 function. Not for human therapeutic use.
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| Molecular Formula |
C16H21N5O
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| Molecular Weight |
299.37
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~1 mg/mL (~3.34 mM; with sonication (<60°C))
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3403 mL | 16.7017 mL | 33.4035 mL | |
| 5 mM | 0.6681 mL | 3.3403 mL | 6.6807 mL | |
| 10 mM | 0.3340 mL | 1.6702 mL | 3.3403 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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