RK-287107 is a potent TNKS/TNKS2 inhibitor (IC50 = 14.4 nM) with >7000-fold selectivity against the PARP1 enzyme, which inhibits WNT-responsive TCF reporter activity and proliferation of human colorectal cancer cell line COLO-320DM. In a mouse xenograft model, RK-287107 also showed dose-dependent inhibition of tumor growth. Tankyrase inhibitors are a new class of anticancer agents, and RK-287107 is a promising lead compound for their development.
Physicochemical Properties
| Molecular Formula | C22H26F2N4O2 |
| Molecular Weight | 416.464251995087 |
| Exact Mass | 416.2 |
| Elemental Analysis | C, 63.45; H, 6.29; F, 9.12; N, 13.45; O, 7.68 |
| CAS # | 2171386-10-8 |
| Related CAS # | 2171386-10-8 |
| PubChem CID | 137701512 |
| Appearance | White to off-white solid powder |
| LogP | 2.2 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 30 |
| Complexity | 762 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | FZQYCOUBRJEYBC-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C22H26F2N4O2/c23-14-11-16(24)19-18(12-14)28(9-10-29)13-22(19)5-7-27(8-6-22)21-25-17-4-2-1-3-15(17)20(30)26-21/h11-12,29H,1-10,13H2,(H,25,26,30) |
| Chemical Name | 2-[4,6-difluoro-1-(2-hydroxyethyl)spiro[2H-indole-3,4'-piperidine]-1'-yl]-5,6,7,8-tetrahydro-3H-quinazolin-4-one |
| Synonyms | RK 287107; RK-287107; RK287107 |
| 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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 | Tankyrase-2 ( IC50 = 10.6 nM ); Tankyrase-1 ( IC50 = 14.3 nM ) |
| ln Vitro | RK-287107 is a novel inhibitor that selectively inhibits tankyrases 1 and 2. In colorectal cancer cells harboring the shortly truncated APC mutations, RK-287107 causes Axin2 accumulation and downregulates β-catenin, T-cell factor/lymphoid enhancer factor reporter activity, and the target gene expression. The growth of APC-mutant (β-catenin-dependent) colorectal cancer COLO-320DM and SW403 cells is consistently inhibited by RK-287107, but not that of APC-wild (β-catenin-independent) colorectal cancer RKO cells. [1] |
| ln Vivo | RK-287107 administered intraperitoneally or orally inhibits the growth of COLO-320DM tumors in NOD-SCID mice. In vivo, RK-287107 inhibits the growth of tumors and the Wnt/β-catenin pathway in xenografted COLO-320DM cells. [1] |
| Cell Assay | RK-287107 is applied to cells in triplicate and left on for 120 hours. MTT assays are used to quantify relative cell number. Plotting of the average values occurs after at least two repetitions of the experiment. |
| Animal Protocol |
6-week-old female NOD.CB17-Prkdcscid/J mice s.c. injected with COLO-320DM cells 100 mg/kg, 150 mg/kg, 300 mg/kg IP, Oral gavage |
| References |
[1]. RK-287107, a potent and specific tankyrase inhibitor, blocks colorectal cancer cell growth in a preclinical model. Cancer Sci. 2018 Dec;109(12):4003-4014. |
Solubility Data
| Solubility (In Vitro) |
DMSO: 83~125 mg/mL (199.3~300.2 mM) Ethanol: ˂1 mg/mL (NaN mM) Water: ˂1 mg/mL (NaN mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.99 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 20.8 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: ≥ 2.08 mg/mL (4.99 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 20.8 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: ≥ 2.08 mg/mL (4.99 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 | 2.4012 mL | 12.0060 mL | 24.0119 mL | |
| 5 mM | 0.4802 mL | 2.4012 mL | 4.8024 mL | |
| 10 mM | 0.2401 mL | 1.2006 mL | 2.4012 mL |