Physicochemical Properties
| Molecular Formula | C43H48N10O6S |
| Molecular Weight | 832.97 |
| Exact Mass | 832.35 |
| Elemental Analysis | C, 62.00; H, 5.81; N, 16.82; O, 11.52; S, 3.85 |
| CAS # | 2688842-08-0 |
| PubChem CID | 146014466 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 4.7 |
| Hydrogen Bond Donor Count | 5 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 16 |
| Heavy Atom Count | 60 |
| Complexity | 1460 |
| Defined Atom Stereocenter Count | 3 |
| SMILES | CC1=C(SC=N1)C2=CC=C(C=C2)CNC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCNC(=O)C4=CC=C(C=C4)C5=CN=C(N6C5=NN=C6)NCC7=CC=CO7)O |
| InChi Key | PPNNFXIBKLCMTI-WXEAQWFJSA-N |
| InChi Code | InChI=1S/C43H48N10O6S/c1-26-36(60-25-48-26)29-11-9-27(10-12-29)20-45-40(57)34-19-31(54)23-52(34)41(58)37(43(2,3)4)50-35(55)8-5-17-44-39(56)30-15-13-28(14-16-30)33-22-47-42(53-24-49-51-38(33)53)46-21-32-7-6-18-59-32/h6-7,9-16,18,22,24-25,31,34,37,54H,5,8,17,19-21,23H2,1-4H3,(H,44,56)(H,45,57)(H,46,47)(H,50,55)/t31-,34+,37-/m1/s1 |
| Chemical Name | (2S,4R)-1-((S)-2-(4-(4-(5-((Furan-2-ylmethyl)amino)-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl)benzamido)butanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide |
| Synonyms | UNC6852; UNC-6852; UNC 6852 |
| 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 | IC50: 247 nM (EED)[1] |
| ln Vitro | PRC2 degradation is mediated by UNC6852 [1]. Even at concentrations up to 30 μM, UNC6852 does not cause death in HeLa cells [1]. Reduced EED and EZH2 levels are the effect of UNC6852 (10 μM; 1-72 hours) [1]. UNC6852 recruits VHL to facilitate PRC2 degradation [1]. EED and EZH2 are specifically degraded by UNC6852[1]. H3K27me3 levels and DLBCL cell proliferation are decreased by UNC6852 [1]. |
| Cell Assay |
Cell Proliferation Assay[1] Cell Types: DLBCL Cells Tested Concentrations: 3 μM Incubation Duration: 0 -10 days Experimental Results: demonstrated anti-proliferative effects. Western Blot Analysis[1] Cell Types: HeLa Cells Tested Concentrations: 10 μM Incubation Duration: 1 hrs (hours), 4 hrs (hours), 8 hrs (hours), 10 hrs (hours), 16 hrs (hours), 20 hrs (hours), 24 hrs (hours), 48 hrs (hours), 72 hrs (hours) Experimental Results: Resulted in a decrease in the levels of both EED and EZH2. |
| References |
[1]. Degradation of Polycomb Repressive Complex 2 with an EED-Targeted Bivalent Chemical Degrader. Cell Chem Biol. 2020 Jan 16;27(1):47-56.e15. |
Solubility Data
| Solubility (In Vitro) | DMSO : 100 mg/mL (120.05 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (6.00 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 50.0 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: ≥ 5 mg/mL (6.00 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 50.0 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: ≥ 5 mg/mL (6.00 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 50.0 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 | 1.2005 mL | 6.0026 mL | 12.0052 mL | |
| 5 mM | 0.2401 mL | 1.2005 mL | 2.4010 mL | |
| 10 mM | 0.1201 mL | 0.6003 mL | 1.2005 mL |