Other grades of this product :
| (3S,6S,12aS)-1,2,3,4,6,7,12,12a-Octahydro-9-methoxy-6-(2-methylpropyl)-1,4-dioxopyrazino[1',2':1,6]pyrido[3,4-b]indole-3-propanoic acid 1,1-dimethylethyl ester Basic information |
| Product Name: | (3S,6S,12aS)-1,2,3,4,6,7,12,12a-Octahydro-9-methoxy-6-(2-methylpropyl)-1,4-dioxopyrazino[1',2':1,6]pyrido[3,4-b]indole-3-propanoic acid 1,1-dimethylethyl ester | | Synonyms: | Pyrazino[1',2':1,6]pyrido[3,4-b]indole-3-propanoic acid, 1,2,3,4,6,7,12,12a-octahydro-9-methoxy-6-(2-methylpropyl)-1,4-dioxo-, 1,1-dimethylethyl ester, (3S,6S,12aS)-(Ko143);Ko 143;(3S,6S,12aS)-1,2,3,4,6,7,12,12a-Octahydro-9-methoxy-6-(2-methylpropyl)-1,4-dioxopyrazino[1',2':1,6]pyrido[3,4-b]indole-3-propanoic acid 1,1-dimethylethyl ester;12a-octahydro-9-Methoxy-6-(2-Methylpropyl)-1;12aS)-;4-b]indole-3-propanoicacid;4-dioxo-;6]pyrido[3 | | CAS: | 461054-93-3 | | MF: | C26H35N3O5 | | MW: | 469.57 | | EINECS: | | Product Categories: | Chiral Reagents;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals | | Mol File: | 461054-93-3.mol |
| (3S,6S,12aS)-1,2,3,4,6,7,12,12a-Octahydro-9-methoxy-6-(2-methylpropyl)-1,4-dioxopyrazino[1',2':1,6]pyrido[3,4-b]indole-3-propanoic acid 1,1-dimethylethyl ester Chemical Properties |
| Melting point | 147 ºC | | Boiling point | 689.8±55.0 °C(Predicted) | | density | 1.24 | | storage temp. | Desiccate at -20°C | | solubility | DMSO: >10mg/mL | | form | powder | | pka | 13.31±0.60(Predicted) | | color | white to off-white | | Stability: | Stable for 2 years from date of purchase as supplied. Protect from exposure to moisture. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months. |
| Hazard Codes | Xi | | Risk Statements | 36/37/38 | | Safety Statements | 26-36 | | WGK Germany | 3 |
| (3S,6S,12aS)-1,2,3,4,6,7,12,12a-Octahydro-9-methoxy-6-(2-methylpropyl)-1,4-dioxopyrazino[1',2':1,6]pyrido[3,4-b]indole-3-propanoic acid 1,1-dimethylethyl ester Usage And Synthesis |
| Description | Breast cancer resistance protein (BCRP) is an ATP-binding cassette protein known also as ABCG2. While it normally functions as a high-capacity urate exporter in the renal system, it also acts as a xenobiotic transporter and contributes to multidrug resistance (e.g., to mitoxantrone) in certain types of cancer. BCRP is abundant at the intestinal epithelium and blood-brain barrier, potentially restricting the distribution of certain drugs. Ko 143 is a potent and selective inhibitor of BCRP, preventing the export of mitoxantrone and topotecan in breast cancer cell lines (EC50s = 23 and 26 nM, respectively). It is much less effective at the transporters P-glycoprotein and multidrug resistance-associated protein 1, MRP1. Ko 143 is effective in vivo in mice. | | Uses | A potent BCRP (breast cancer resistance protein) inhibitor | | Uses | Ko143 hydrate has been used:- to determine the role of ATP-binding cassette sub-family G member 2 (ABCG2), human embryonic kidney (HEK)-C1 and HEK-ABCG2 in tumor microenvironment
- to inhibit ABCG2 for sphere formation assay
- in calcein-AM efflux inhibition to monitor multidrug resistance protein (MRP)-function in kidney
- for cell viability assay
| | Biological Activity | Potent and selective breast cancer resistance protein multidrug transporter (BCRP) inhibitor (EC 90 = 26 nM). Displays > 200-fold selectivity over P-gp and MRP-1 transporters. Increases intracellular drug accumulation and reverses BCRP-mediated multidrug resistance. | | Biochem/physiol Actions | Ko143 has been used as a positive control inhibitor on functions of breast cancer resistance protein (BCRP) using a BCRP prototypical substrate mitoxantrone. BCRP, an ABCG2 transporter, plays an important role in disposition of many drugs and environmental toxins. Ko143 displays > 200-fold selectivity over P-gp and MRP-1 transporters and thus is more specific than other known BCRP inhibitors such as fumitremorgin C and GF120918. It increases intracellular drug accumulation and reverses BCRP-mediated multidrug resistance. It blocks topotecan and ABZSO transport in a concentration-dependent manner. | | References | 1) Allen et al. (2002), Potent and specific inhibition of breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C; Mol. Cancer Ther., 1 417
2) Weidner et al. (2015), The Inhibitor Ko143 Is Not Specific for ABCG2; J. Pharmacol. Exp. Ther., 354 384
3) Palasuberniam et al. (2015), ABCG2 transporter inhibitor restores the sensitivity of triple negative breast cancer cells to aminolevulinic acid-mediated photodynamic therapy; Sci. Rep., 5 13298
4) Moreno-Sanz et al. (2011), The ABC membrane transporter ABCG2 prevents access of FAAH inhibitor URB937 to the central nervous system; Pharmacol. Res., 64 359
5) Sabnis et al. (2017),?The Efflux Transporter ABCG2 Maintains Prostate Stem Cells;? Mol. Cancer Res., 15 128 |
| (3S,6S,12aS)-1,2,3,4,6,7,12,12a-Octahydro-9-methoxy-6-(2-methylpropyl)-1,4-dioxopyrazino[1',2':1,6]pyrido[3,4-b]indole-3-propanoic acid 1,1-dimethylethyl ester Preparation Products And Raw materials |
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![(3S,6S,12aS)-1,2,3,4,6,7,12,12a-Octahydro-9-methoxy-6-(2-methylpropyl)-1,4-dioxopyrazino[1',2':1,6]pyrido[3,4-b]indole-3-propanoic acid 1,1-dimethylethyl ester](/img/461054-93-3.jpg "(3S,6S,12aS)-1,2,3,4,6,7,12,12a-Octahydro-9-methoxy-6-(2-methylpropyl)-1,4-dioxopyrazino[1',2':1,6]pyrido[3,4-b]indole-3-propanoic acid 1,1-dimethylethyl ester")
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