Physicochemical Properties
| CAS # | 3029515-97-4 |
| Appearance | Off-white to light yellow solid powder |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | AlkB homologue 5 (ALKBH5) IC50: 2.97 μM[1] |
| 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] |
| 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 |
| 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. |
| 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. |
| References |
[1].Discovery of Pyrazolo[1,5-a]pyrimidine Derivative as a Novel and Selective ALKBH5 Inhibitor for the Treatment of AML. Journal of Medicinal Chemistry. 2023，Article ASAP. |
Solubility Data
| Solubility (In Vitro) | DMSO :~125 mg/mL (~216.09 mM; with sonication) |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |