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| Targets |
AlkB homologue 5 (ALKBH5) IC50: 2.97 μM[1]
DDO-2728 targets ALKBH5 (AlkB homolog 5), a demethylase that removes N6-methyladenosine (m6A) modifications from RNA. m6A is the most abundant internal modification in eukaryotic mRNA and plays a critical role in RNA metabolism, including splicing, translation, and stability. ALKBH5 is overexpressed in various cancers, including AML, and its inhibition can restore m6A levels, leading to altered gene expression and anti-cancer effects. |
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| ln Vitro |
DDO-2728 (0-40 μM, 48 h) increases m6A methylation levels in MOLM-13, HEK293 and MV4-11 cells over a concentration gradient [1]. DDO-2728 (0.01-100 μM, 72 h) can inhibit the proliferation of MOLM-13 and MV4-11 cells with IC50s of 0.45 and 1.2 μM respectively, and its toxicity to HEK293 and HUVEC is relatively weak [1]. DDO-2728 (20 μM, 48 h) significantly blocks the cell cycle of MOLM-13 and MV4-11 cells in the G1/M phase [1]. DDO-2728 (5, 10 μM, 48 h) induces apoptosis in MV4−11 and MOLM-13 cells in a concentration-dependent manner [1]. DDO-2728 (20 μM, 24 h) reduces the half-life of TACC3 mRNA in MOLM-13 and MV4−11 cells [1]. DDO-2728 (0-10 μM, 48 h) significantly reduces the abundance of TACC3 and c-Myc in MOLM-13 and MV4-11 cells at the mRNA and protein levels [1]. 1.19 Metabolic stability of rat and human plasma and liver microsomes [1]
In vitro, DDO-2728 inhibits ALKBH5 with an IC50 of 2.97 μM. It increases m6A modification levels in AML cells, leading to altered expression of genes involved in cell proliferation and survival. The compound induces apoptosis and cell cycle arrest in AML cells. Its antiproliferative activity has been demonstrated in various AML cell lines. The compound's selectivity for ALKBH5 over other demethylases contributes to its specificity. |
| ln Vivo |
DDO-2728 (10-40 mg/kg, intraperitoneal injection, once daily, for 14 days) can effectively inhibit the growth of MV4−11 xenograft tumors in nude mice [1]. 1.19 Pharmacokinetic parameters of DDO-2728 in rats[1] Parameter Rat (iv, 2mg/kg) Rat (ip, 10mg/kg) T1/2 (min) 36.7 ± 3.2 148.3 ± 4.6 Cmax (ng/mL) 13388.3 ± 784.5 2337.5 ± 295.7 Tmax (min) 30 AUC0-∞ (min·μg/mL) 404.3 ± 58.6 349.1 ± 26.1 Vz_F_obs (mL/kg) 263.6 ± 17.5 6177.6 ± 650.2 Cl_F_obs (mL/min/kg) 5.0 ± 0.5 28.8 ± 2.2 MRT (min) 77.8 ± 15.5 168.2 ± 1.2 F (%) 17.3
In vivo, DDO-2728 has demonstrated anti-tumor efficacy in MV4-11 xenograft models. By inhibiting ALKBH5 and increasing m6A levels, the compound suppresses tumor growth in AML models. The compound's efficacy in xenograft models highlights its potential application in cancer research and therapeutic strategies targeting ALKBH5. Detailed in vivo efficacy data are described in the primary literature. |
| Enzyme Assay |
Non-cellular binding assays for DDO-2728 involve measuring its inhibitory activity against purified ALKBH5 enzyme. The demethylase activity of ALKBH5 is assessed using m6A-containing RNA substrates, and the production of demethylated RNA is quantified. The compound's IC50 is determined by measuring enzyme activity in the presence of varying concentrations of DDO-2728. Selectivity against other demethylases can also be evaluated.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: MOLM-13, MV4-11, HEK293, HUVEC Tested Concentrations: 0.01-100 μM Incubation Duration: 72 h Experimental Results: Inhibited the proliferation of MOLM-13 and MV4−11 cells with IC50s of 0.45 and 1.2 μM respectively, didn't show visual cytotoxicity in HEK293 and HUVECs under 1 μM. Apoptosis Analysis[1] Cell Types: MOLM-13 , MV4-11 Tested Concentrations: 0, 5, 10 μM Incubation Duration: 48 h Experimental Results: Induced cell apoptosis of MV4−11 and MOLM-13 cells concentration-dependently, apoptosis rate for MV4−11 increased from 7.17% to 55.4%, apoptosis rate for MOLM-13 increased from 6.49% to 31.5%. Cell Cycle Analysis[1] Cell Types: MOLM-13, MV4-11 Tested Concentrations: 20 μM Incubation Duration: 48 h Experimental Results: Arrested the cell cycle of MOLM-13 and MV4 −11 cells at the G1/M phase as no G2/M phase cells exist. In vitro cellular experiments with DDO-2728 are conducted in AML cell lines such as MV4-11. Cells are treated with the compound at various concentrations, and m6A levels in total RNA are quantified using m6A-specific antibodies or LC-MS/MS. Cell viability, proliferation, and apoptosis are evaluated using standard assays such as CellTiter-Glo, MTT, and Annexin V staining. Cell cycle analysis is performed by flow cytometry. |
| Animal Protocol |
Animal/Disease Models: MV4−11 xenograft nude mice [1]
Doses: 10, 20, and 40 mg/kg Route of Administration: Intraperitoneal injection (i.p.) daily for 14 d Experimental Results: Inhibited tumor growth significantly even at a concentration of 10 mg/kg. No significant change in the weight of the mice and the main organs during the treatment, the organ weight of test group mice was the same as vehicle group, no obvious injury damage was observed in the HE staining images of organ tissues. In vivo animal studies for DDO-2728 are performed in murine xenograft models using MV4-11 AML cells. Tumor-bearing mice are treated with the compound via appropriate routes of administration. Tumor growth is monitored over time, and endpoints include tumor volume measurements, survival analysis, and pharmacodynamic assessments of m6A levels and ALKBH5 target gene expression in tumor tissues. Efficacy is compared to vehicle controls. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of DDO-2728 include a molecular formula of C28H17F3N4O7. The CAS number is 3029515-97-4. The compound appears as a solid powder. Detailed pharmacokinetic parameters such as half-life, bioavailability, and tissue distribution would be determined in appropriate animal models. Storage conditions should follow the supplier's recommendations. The compound is for research use only.
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| Toxicity/Toxicokinetics |
Toxicity data for DDO-2728 are generated during preclinical development. As an ALKBH5 inhibitor, potential toxicities may include effects on RNA metabolism in normal tissues. Comprehensive toxicology studies would assess safety margins and identify target organ toxicities. Researchers should consult the safety data sheet and handle the compound with appropriate laboratory safety precautions for research use only.
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| References | |
| Additional Infomation |
DDO-2728 is a selective ALKBH5 inhibitor. It increases m6A modification levels in AML cells and exhibits antiproliferative activity. It has demonstrated anti-tumor efficacy in MV4-11 xenograft models. The compound has potential applications in cancer research and therapeutic strategies targeting ALKBH5. All products are for research use only and not for human therapeutic applications.
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| CAS # |
3029515-97-4
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| Appearance |
Off-white to light yellow 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 :~125 mg/mL (~216.09 mM; with sonication)
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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.) |
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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