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Purity: ≥98%
D-64131, an aroylindole analog, is a novel, oral and potent inhibitor of tubulin polymerization. D-64131 competitively binds to the colchicine binding site of αβ-Tubulin, acting as a mitotic inhibitor. When tested against the human HeLa/KB cervical, SK-OV-3 ovarian, and U373 astrocytoma carcinoma cell lines, it demonstrated high cytotoxicity at IC(50) = 20 to 75 nM. The arrest of the cell cycle in the G2/M phase was correlated with the inhibition of proliferation. D-64131 is administered orally in vivo to inhibit the growth of tumor models in mice. D-64131 shows great promise as a cancer treatment agent.
| Targets |
tubulin polymerization (IC50 = 0.53 μM)
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| ln Vitro |
D-64131 is antimitotic because it binds to β-tubulin, which causes microtubules to become unstable and stops mitotic cells in the M-phase[1].
D-64131 inhibits tumor cell proliferation from 12 out of 14 distinct organs and tissues, with mean IC50 values of 62 nM[1]. D-64131 is cytotoxic to tumor cell lines that are MDR/MRP[1]. D-64131 inhibits the cell cycle and proliferation of U373 at IC50s of 74 nM and 62.7 nM, respectively[2]. |
| ln Vivo |
D-64131 (200-400 mg/kg; p.o.; daily; days 1-5, 8-9, and 15-18) significantly reduces the growth of tumors in the human amelanoic melanoma MEXF 989 tumor xenograft mice model[1].
D-64131 is well tolerated and has oral bioavailability at efficacious doses[1]. |
| Enzyme Assay |
Using biotin-labeled tubulin, streptavidin-coated yttrium SPA beads, and [3H]colchicine (1 mCi/ml; specific activity, 76.5 Ci/mmol), the tubulin binding assay was carried out in accordance with Tahit et al. In a nutshell, the binding mixture consists of 100 μl of G-PEM buffer, pH 6.9 (80 mm PIPES, 1 mm MgCl2, 1 mm EGTA, and 5% glycerol), 0.08 μm [3H]colchicine, 1 mm GTP, and 0.5 μg of biotin-tubulin. Prior to adding tubulin, the test compound and [3H]colchicine were added. Following a 2-hour incubation period at 37°C, 20 μl of SPA beads (80 μg in P-GEM buffer) were introduced. The SPA beads were allowed to settle for 45 minutes at room temperature after an additional 30 minutes of agitation incubation. Scintillation counting was then performed using a MicroBeta Trilux counting apparatus.
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| Cell Assay |
D-64131 is administered orally in vivo to inhibit the growth of tumor models in mice. To achieve a final DMSO concentration of 10%, D-64131 was first freshly dissolved in DMSO and then diluted with PBS containing 0.05% v/v Tween 80. For all experiments, 6–8 week old outbred nude mice with an NMRI genetic background were utilized. Based on the vitroselectivity of D-64131 toward melanoma (data not shown), the human amelanoic melanoma MEXF 989 tumor xenograft model was selected for the experiments. The tumors were engrafted from serial passage growing s.c. in nude mice. Approximately 25 mg of fragments were s.c. implanted in each of the animals' flanks. Details of the animal experiments and data analysis were described by Mahboobi et al. The 200 and 400 mg/kg/day doses were administered p.o. to the tumor-bearing, nude MEXF 989 mice on days 1-4, 8-9, and 15-18. Before beginning tumor experiments, it was established that the medication dosages and treatment plan employed in two separate studies were well tolerated by non-tumor bearing nude mice.
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| Animal Protocol |
Outbred nude mice (6-8 weeks), human amelanoic melanoma MEXF 989 tumor xenograft model[1]
200 mg/kg, 400 mg/kg Oral administration, daily, on days 1-5, 8-9, and 15-18 after xenograft |
| References | |
| Additional Infomation |
(5-methoxy-1H-indol-2-yl)-phenylmethanone is a N-acylindole.
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| Molecular Formula |
C16H13NO2
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|---|---|---|
| Molecular Weight |
251.28
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| Exact Mass |
251.094
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| Elemental Analysis |
C, 76.48; H, 5.21; N, 5.57; O, 12.73
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| CAS # |
74588-78-6
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| Related CAS # |
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| PubChem CID |
3921152
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
455.2±25.0 °C at 760 mmHg
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| Flash Point |
229.1±23.2 °C
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| Vapour Pressure |
0.0±1.1 mmHg at 25°C
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| Index of Refraction |
1.657
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| LogP |
2.65
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
19
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| Complexity |
325
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C([H])([H])[H])C1C([H])=C([H])C2=C(C=1[H])C([H])=C(C(C1C([H])=C([H])C([H])=C([H])C=1[H])=O)N2[H]
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| InChi Key |
ICMIJSRDISNKOC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H13NO2/c1-19-13-7-8-14-12(9-13)10-15(17-14)16(18)11-5-3-2-4-6-11/h2-10,17H,1H3
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| Chemical Name |
(5-methoxy-1H-indol-2-yl)-phenylmethanone
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9796 mL | 19.8981 mL | 39.7962 mL | |
| 5 mM | 0.7959 mL | 3.9796 mL | 7.9592 mL | |
| 10 mM | 0.3980 mL | 1.9898 mL | 3.9796 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.
 Inhibition of tubulin polymerization and [3H]colchicine binding.Cancer Res.2002 Jun 1;62(11):3113-9. |
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 Cell cycle specificity.Cancer Res.2002 Jun 1;62(11):3113-9. |
 Effect ofd-64131 on the human melanoma MEXF 989 tumor xenograft.Cancer Res.2002 Jun 1;62(11):3113-9. |
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