Physicochemical Properties
| Molecular Formula | C23H30N6O3S2 |
| Molecular Weight | 502.65 |
| Exact Mass | 502.182 |
| CAS # | 2107280-55-5 |
| PubChem CID | 122491414 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 3 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 11 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 34 |
| Complexity | 609 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | NC1=CC(N)=NC(=N1)S[C@H](C)C1N=C(SC=1C)C1C=CC(=C(OCCN2CCOCC2)C=1)OC |
| InChi Key | MFVINMPRHHUSBW-OAHLLOKOSA-N |
| InChi Code | InChI=1S/C23H30N6O3S2/c1-14-21(15(2)34-23-26-19(24)13-20(25)27-23)28-22(33-14)16-4-5-17(30-3)18(12-16)32-11-8-29-6-9-31-10-7-29/h4-5,12-13,15H,6-11H2,1-3H3,(H4,24,25,26,27)/t15-/m1/s1 |
| Chemical Name | 2-[(1R)-1-[2-[4-methoxy-3-(2-morpholin-4-ylethoxy)phenyl]-5-methyl-1,3-thiazol-4-yl]ethyl]sulfanylpyrimidine-4,6-diamine |
| 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 | EC50: 10.2 nM (dCK)[1] |
| ln Vitro | For the purpose of suppressing dCK activity in CEM T-ALL cells, (S)-DI-87 has a larger IC50 value (IC50=468 nM) (IC50=3.15 nM) than DI-87 ((R)-DI-8) [1]. When gemcitabine, a dCK-dependent nucleoside analog prodrug with an EC50 of 10.2 nM, is applied to human cell line CCRF-CEM (CEM) cells for 72 hours, DI-87 (1 μM) protects the cells against its antiproliferative effects[1]. |
| ln Vivo | Oral gavage of DI-87 (5-25 mg/kg) results in total inhibition of dCK within 27 hours, and full recovery of enzyme function by 36 hours at the 25 mg/kg dose[1]. Plasma concentrations of DI-87 (10–50 mg/kg; oral) range from 1 to 3 hours, while its plasma half-life is 4 hours[1]. Growth of male NSG mice with CEM tumors with DI-87 (10 mg/kg/day or 25 mg/kg/day; oral; for 16–18 days) in combination with thymidine (2 g/kg; intraperitoneally; twice daily) decreases tumor engraftment[1]. |
| Animal Protocol |
Animal/Disease Models: 8-12 week-old male or female NSG mice with CEM tumor xenografts[1] Doses: 5, 10, 25 mg/kg Route of Administration: po (oral gavage) Experimental Results: The 25 mg/kg dose demonstrated full dCK inhibition for 27 hrs (hours) , and enzyme activity fully recovered by 36 hrs (hours). The 10 mg/kg dose resulted in full inhibition with recovery initiating at the 12 hrs (hours) time point. The 5 mg/kg dose resulted in minimal dCK inhibition with rapid recovery. Animal/Disease Models: Female NSG mice with CEM tumors[1] Doses: 10, 25, or 50 mg/kg Route of Administration: Oral Experimental Results: Had plasma concentrations of between 1 and 3 hrs (hours) and plasma half-life of 4 hrs (hours). Had tumor concentrations lower than plasma and had a later, more sustained peak at 3-9 hrs (hours). |
| References |
[1]. Development and Preclinical Pharmacology of a Novel dCK Inhibitor, DI-87. Biochem Pharmacol. 2020 Feb;172:113742. |
| Additional Infomation | Deoxycytidine Kinase Inhibitor TRE-515 is an orally bioavailable inhibitor of deoxycytidine kinase (dCK), with potential antineoplastic activity. Upon oral administration, dCK inhibitor TRE-515 targets, binds to and inhibits the activity of dCK, an enzyme that catalyzes the rate-limiting reaction in the deoxyribonucleoside salvage pathway in cancer cells. By inhibiting dCK, TRE-515 halts nucleotide synthesis and prevents the metabolism of DNA precursors in tumor cells. This inhibits DNA replication in and proliferation of cancer cells. dCK predominantly phosphorylates the deoxyribonucleoside deoxycytidine (dC) and converts dC into deoxycytidine monophosphate. It is upregulated in multiple tumor cell types in response to increased DNA synthesis needed for rapid cancer cell proliferation. |
Solubility Data
| Solubility (In Vitro) | DMSO: 145 mg/mL (288.47 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.97 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (4.97 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (4.97 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9895 mL | 9.9473 mL | 19.8946 mL | |
| 5 mM | 0.3979 mL | 1.9895 mL | 3.9789 mL | |
| 10 mM | 0.1989 mL | 0.9947 mL | 1.9895 mL |