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| Targets |
Tankyrase-2 ( IC50 = 10.6 nM ); Tankyrase-1 ( IC50 = 14.3 nM )
RK-287107 targets tankyrase-1 (TNKS1) and tankyrase-2 (TNKS2), which are poly(ADP-ribose) polymerases (PARPs) that regulate Wnt/β-catenin signaling by promoting the degradation of Axin. By inhibiting tankyrase, RK-287107 stabilizes Axin, leading to increased β-catenin degradation and downregulation of Wnt signaling. It has >7000-fold selectivity against PARP1. It selectively inhibits APC-mutated (β-catenin-dependent) colorectal cancer cells. |
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| 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]
In vitro, RK-287107 (0.03-10 μM; 16 hours) downregulates β-catenin signaling in cultured cells and induces the accumulation of tankyrase and Axin1/2. It displays an antiproliferative effect on colorectal cancer cells harboring APC mutations, with a GI50 value of 0.449 μM on COLO-320DM cells. It has IC50 values of 14.3 nM for tankyrase-1 and 10.6 nM for tankyrase-2. |
| 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]
In vivo, RK-287107 (100 and 300 mg/kg; i.p. administration; once per day; 5-days on/2-days off schedule for 2 weeks) inhibits tumor growth in a mouse xenograft model. It blocks colorectal cancer cell growth. Its efficacy in inhibiting Wnt/β-catenin-driven tumor growth has been demonstrated in preclinical models. |
| Enzyme Assay |
Cell-free assays for RK-287107 measure its inhibition of tankyrase enzymatic activity. Purified tankyrase-1 or tankyrase-2 is incubated with a substrate (e.g., biotinylated PARP substrate) and NAD+ in the presence of varying concentrations of RK-287107, and the extent of PARylation is measured. The IC50 for inhibition is determined. Its selectivity against PARP1 is confirmed.
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| 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.
Cellular assays for RK-287107 are performed using colorectal cancer cell lines, such as COLO-320DM (APC-mutated) and RKO (APC-wild type). Cells are treated with varying concentrations of RK-287107, and cell viability is measured by MTT or CellTiter-Glo assays. Wnt/β-catenin signaling is assessed by TCF reporter assays. β-catenin, Axin, and tankyrase protein levels are measured by Western blotting. |
| 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 In vivo animal experiments for RK-287107 are conducted in mouse xenograft models of colorectal cancer. Immunocompromised mice are implanted with COLO-320DM cells and treated with RK-287107 via intraperitoneal administration at 100 and 300 mg/kg. Tumor growth inhibition is monitored. Pharmacodynamic markers such as β-catenin and Axin levels in tumor tissues are assessed. |
| ADME/Pharmacokinetics |
RK-287107 has a molecular weight of 416.46 g/mol and a molecular formula of C22H26F2N4O2. It has a density of 1.48 g/cm3 (predicted) and is a white solid. It is soluble in DMSO at 120 mg/mL (288.14 mM). For in vivo formulation, it can be prepared in 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% Saline at 4 mg/mL (9.6 mM). The powder is stable for 3 years at -20°C.
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| Toxicity/Toxicokinetics |
The toxicological profile of RK-287107 has not been extensively characterized. As a tankyrase inhibitor, it may have effects on Wnt signaling in normal tissues. No significant toxicity has been reported in the available literature. Standard toxicology studies would be necessary to establish its safety profile. It is a research compound and is not intended for human use.
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| References | |
| Additional Infomation |
RK-287107 is a specific and effective tankyrase inhibitor with potential for treating Wnt-driven cancers. It is also known as RK287107. It inhibits tankyrase-1 and tankyrase-2 with IC50 values of 14.3 and 10.6 nM, respectively. It has >7000-fold selectivity against PARP1. It blocks colorectal cancer cell growth. It is a research compound and is not approved for clinical use.
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| Molecular Formula |
C22H26F2N4O2
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| Molecular Weight |
416.464251995087
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| Exact Mass |
416.2
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| Elemental Analysis |
C, 63.45; H, 6.29; F, 9.12; N, 13.45; O, 7.68
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| CAS # |
2171386-10-8
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| Related CAS # |
2171386-10-8
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| PubChem CID |
137701512
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| Appearance |
White to off-white solid powder
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
30
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| Complexity |
762
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CCC2=C(C1)C(=O)NC(=N2)N3CCC4(CC3)CN(C5=C4C(=CC(=C5)F)F)CCO
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| InChi Key |
FZQYCOUBRJEYBC-UHFFFAOYSA-N
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| 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)
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| 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
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| Synonyms |
RK 287107; RK-287107; RK287107
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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) |
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| 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. View More
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. |
| 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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