UC-514321 (UC514321), an analog of NSC370284, is more effective than NSC-370284 as an inhibitor of STAT/TET1. It acts by directly binding to STAT3/5 and suppressing the viability of AML cells with high level of TET1 expression both in vitro and in vivo.
Physicochemical Properties
| Molecular Formula | C26H35NO5 |
| Molecular Weight | 441.559808015823 |
| Exact Mass | 441.251 |
| CAS # | 299420-83-0 |
| PubChem CID | 339892 |
| Appearance | White to off-white solid powder |
| LogP | 5.5 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 32 |
| Complexity | 599 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O1CCN(CC1)C(C1=C(C=C2C(=C1)OCO2)O)C1C=C(C(=C(C=1)C(C)(C)C)O)C(C)(C)C |
| InChi Key | XNARHFDDQALZPZ-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C26H35NO5/c1-25(2,3)18-11-16(12-19(24(18)29)26(4,5)6)23(27-7-9-30-10-8-27)17-13-21-22(14-20(17)28)32-15-31-21/h11-14,23,28-29H,7-10,15H2,1-6H3 |
| Chemical Name | 6-[(3,5-ditert-butyl-4-hydroxyphenyl)-morpholin-4-ylmethyl]-1,3-benzodioxol-5-ol |
| Synonyms | UC514321 UC 514321 |
| 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
| ln Vitro | UC-514321 causes AML cells to undergo more apoptosis, but not normal HSPCs[1]. The suppression of AML cell viability by UC-514321 (0-500 nM, 48 hours) is dependent on TET1 signaling [1]. |
| ln Vivo | In an AML mouse model, UC-514321 (2.5 mg/kg, ip, once daily for 10 days) shows better anti-tumor activity than NSC370284 [1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: MONOMAC-6, THP-1, KOCL-48, KASUMI-1, ML-2, and NB4 cells. Tested Concentrations: 0-500 nM. Incubation Duration: 48 hrs (hours). Experimental Results: Most Dramatically repressed MONOMAC-6 cell viability. demonstrated no inhibitory effect on the viability of TET1-low AML. RT-PCR[1] Cell Types: MONOMAC-6 cells. Tested Concentrations: 0-500 nM. Incubation Duration: 48 hrs (hours). Experimental Results: Functioned as TET1-transcription inhibitors in TET1-high AMLs and their anti-leukemic effects are TET1-dependent. |
| Animal Protocol |
Animal/Disease Models: MLL-AF9-AML mice and AE9a-AML model[1]. Doses: 2.5 mg/kg. Route of Administration: IP., once per day, for 10 days. Experimental Results: demonstrated an improved therapeutic effect in AML mouse models in vivo. Prolonged the median survival over three fold. |
| References |
[1]. Targeted inhibition of STAT/TET1 axis as a therapeutic strategy for acute myeloid leukemia. Nat Commun. 2017 Dec 13;8(1):2099. |
Solubility Data
| Solubility (In Vitro) |
Ethanol : ~50 mg/mL (~113.23 mM) DMSO : ~25 mg/mL (~56.62 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.66 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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 2: ≥ 2.5 mg/mL (5.66 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 | 2.2647 mL | 11.3235 mL | 22.6470 mL | |
| 5 mM | 0.4529 mL | 2.2647 mL | 4.5294 mL | |
| 10 mM | 0.2265 mL | 1.1323 mL | 2.2647 mL |