UC2288 is a novel, cell-permeable, orally bioavailable, potent and selective active p21 attenuator. UC2288 suppresses the growth of several other cancer cell lines as well as kidney cancer cell lines (GI50 = about 10 µM). This new p21 inhibitor will be crucial for understanding how p21 functions, and with more research, it might even find its way into the clinic.
Physicochemical Properties
| Molecular Formula | C20H18CLF6N3O2 |
| Molecular Weight | 481.819244861603 |
| Exact Mass | 481.1 |
| Elemental Analysis | C, 49.86; H, 3.77; Cl, 7.36; F, 23.66; N, 8.72; O, 6.64 |
| CAS # | 1394011-91-6 |
| Related CAS # | 1394011-91-6 |
| PubChem CID | 60196635 |
| Appearance | White to off-white solid powder |
| LogP | 5.6 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 32 |
| Complexity | 627 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | ISPSOOYSNVVMMB-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C20H18ClF6N3O2/c21-16-7-4-13(9-15(16)20(25,26)27)30-18(31)29-12-2-5-14(6-3-12)32-17-8-1-11(10-28-17)19(22,23)24/h1,4,7-10,12,14H,2-3,5-6H2,(H2,29,30,31) |
| Chemical Name | 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[4-[5-(trifluoromethyl)pyridin-2-yl]oxycyclohexyl]urea |
| Synonyms | UC-2288; UC-2288; UC2288 |
| 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 | p21 |
| ln Vitro | While it has no effect on other proteins, UC2288 (0-10 μM; 24 hours) lowers the levels of the protein p21 [1]. In a 24-hour period, UC2288 (0-10 μM) decreases p21 mRNA that is either anticipated or post-expressed, without affecting p53[1]. |
| ln Vivo | Imetelstat and UC2888 (peritoneal gavage; 15 mg/kg; three times per week; four weeks) can be given together to greatly slow the growth of tumors in mice without changing their body weight [2]. MPTP-treated mice exhibit less behavioral impairment and less MAPK activation in their brains when treated with UC2288 (ip; 10 mg/kg; 4 times on 7 days). In the brains of MPTP-treated mice, MPTP treatment raised levels of TNF-α, IL-6, and IL-1β; however, UC2288 significantly decreased MPTP-induced levels of TNF-α, IL-6, but not IL-1β. [3]. |
| Cell Assay |
Western Blot Analysis[1] Cell Types: HK2 (normal kidney), 786-O (RCC), Caki-1 (RCC), ACHN (RCC) and HEY (ovarian cancer) cell Tested Concentrations: 0 μM; ]. 1μM; 3μM; 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: diminished p21 protein expression. RT-PCR[1] Cell Types: p53 mutated RCC cell line 786-O Tested Concentrations: 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Reduction of p21 mRNA, independent of p53 expression. |
| Animal Protocol |
Animal/Disease Models: Eightweeks old athymic nude mice (NCr nu/nu) were injected subcutaneously (sc) (sc) with HCT116 and ACHN cancer cells (2.5x106) [2] Doses: 15 mg/kg Route of Administration: po (oral gavage); 3 times a week; 4 weeks ; Results of combined treatment with imetelstat: Combined treatment with imetelstat can synergistically inhibit tumor growth in mice. Animal/Disease Models: MPTP-induced C57BL6 Parkinson's disease mouse model [3] Doses: 10 mg/kg Route of Administration: intraperitoneal (ip) injection; 4 times within 7 days Experimental Results: Improved MPTP-induced PD progression by inhibiting neuroinflammation. |
| References |
[1]. A Novel p21 Attenuator Which Is Structurally Related to Sorafenib. Cancer Biol Ther. 2013 Mar;14(3):278-85. [2]. Synergistic tumor suppression by combined inhibition of telomerase and CDKN1A. Proc Natl Acad Sci U S A. 2014 Jul 29;111(30):E3062-71. [3]. p21 inhibitor UC2288 ameliorates MPTP induced Parkinson’s disease progression through inhibition of oxidative stress and neuroinammation. Translational Medicine.Neurobiology of Disease. |
Solubility Data
| Solubility (In Vitro) |
DMSO: 50~96 mg/mL (199.2~103.8 mM) Ethanol: 12.5~21 mg/mL (25.9~43.6 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.32 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 20.8 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 | 2.0755 mL | 10.3773 mL | 20.7546 mL | |
| 5 mM | 0.4151 mL | 2.0755 mL | 4.1509 mL | |
| 10 mM | 0.2075 mL | 1.0377 mL | 2.0755 mL |