Ko 143 |
| Catalog No.GC12711 |
Ko 143 is a potent and selective inhibitor of breast cancer resistance protein (BCRP; ABCG2) with an IC50 value of 23nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 461054-93-3
Sample solution is provided at 25 µL, 10mM.
Ko 143 is a potent and selective inhibitor of breast cancer resistance protein (BCRP; ABCG2) with an IC50 value of 23nM[1]. BCRP is an important transmembrane efflux transporter in the body and belongs to the ATP-binding cassette transporter superfamily. It is mainly responsible for the excretion of endogenous and exogenous substances into the extracellular space[2]. The selectivity of Ko 143 is more than 200 times that of P-glycoprotein (P-gp) and multidrug resistance protein-1 (MRP-1)[3].
In vitro, Ko 143 (1.5µM) treatment of U251-V cells expressing ABCG2 for 4h inhibited ABCG2 and restored the intracellular accumulation of the photosensitizer dihydrochlorin e6 (Ce6)[4]. Ko 143 (1μM) treatment of MCF7 cells significantly increased the intracellular fluorescence of mitoxantrone[5]. Treatment of HeLa1A1 cells expressing UGT1A1 with Ko 143 (5, 20μM) significantly reduced the cellular excretion of DMC-O-glucuronide[6].
In vivo, oral treatment of Mdr1a/1b-/- mice with Ko 143 (10mg/kg) increased the oral availability of topotecan and increased its plasma concentration by 4-6 fold at 30 and 60min after administration[7].
References:
[1] Yu Q, Dehghani-Ghahnaviyeh S, Rasouli A, et al. Modulation of ABCG2 Transporter Activity by Ko143 Derivatives[J]. ACS Chemical Biology, 2024, 19(11): 2304-2313.
[2] Choudhuri S, Klaassen C D. Structure, function, expression, genomic organization, and single nucleotide polymorphisms of human ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP) efflux transporters[J]. International journal of toxicology, 2006, 25(4): 231-259.
[3] Lustig S D, Kodali S K, Longo S L, et al. Ko143 reverses MDR in glioblastoma via deactivating P-glycoprotein, sensitizing a resistant phenotype to TMZ treatment[J]. Anticancer Research, 2022, 42(2): 723-730.
[4] Gaber S A A, Müller P, Zimmermann W, et al. ABCG2-mediated suppression of chlorin e6 accumulation and photodynamic therapy efficiency in glioblastoma cell lines can be reversed by KO143[J]. Journal of Photochemistry and Photobiology B: Biology, 2018, 178: 182-191.
[5] Wang J S, Zhu H J, Markowitz J S, et al. Antipsychotic drugs inhibit the function of breast cancer resistance protein[J]. Basic & clinical pharmacology & toxicology, 2008, 103(4): 336-341.
[6] Zhang B, Yang J, Qin Z, et al. Mechanism of the efflux transport of demethoxycurcumin-O-glucuronides in HeLa cells stably transfected with UDP-glucuronosyltransferase 1A1[J]. Plos one, 2019, 14(5): e0217695.
[7] Allen J D, Van Loevezijn A, Lakhai J M, et al. Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C[J]. Molecular cancer therapeutics, 2002, 1(6): 417-425.
| Cell experiment [1]: | |
Cell lines | U251-V cells、U251-EV cells |
Preparation Method | Cells were plated at a density of 1x104 per well in flat bottom 96-well plates in 6 replicates per data point and grown for 6-8h in medium with 10% fetal calf serum (FCS). Sensitization of the cells with 5 or 10µM Chlorin e6 (Ce6) with or without 1.5µM Ko 143 was performed for 4h in 100µL of fresh medium with 2% FCS. The medium was replaced with 100µL of medium without phenol red containing supplements and 2% serum as listed above. At the end of the incubation period, cells were gently washed with pre-warmed PBS and supplied with serum free DMEM medium without phenol red. After irradiation with a series of light doses (0.5-8J/cm2), cells were incubated in 10% FCS-containing DMEM medium for 4h at 37°C in the incubator. For each experiment, a dark control was included in which cells were incubated with Ce6, but not irradiated. |
Reaction Conditions | 1.5µM; 4h |
Applications | Ko 143 significantly reduced the cellular excretion of Ce6. |
References: | |
| Cas No. | 461054-93-3 | SDF | |
| Chemical Name | tert-butyl 3-((3R,6S,12aR)-6-isobutyl-9-methoxy-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino[1',2':1,6]pyrido[3,4-b]indol-3-yl)propanoate | ||
| Canonical SMILES | O=C1N2[C@@H](CC(C)C)C(NC3=C4C=CC(OC)=C3)=C4C[C@@H]2C(N[C@@H]1CCC(OC(C)(C)C)=O)=O | ||
| Formula | C26H35N3O5 | M.Wt | 469.59 |
| Solubility | 30mg/mL in ethanol; 20mg/mL in DMSO; 25mg/mL in DMF | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1295 mL | 10.6476 mL | 21.2952 mL |
| 5 mM | 0.4259 mL | 2.1295 mL | 4.259 mL |
| 10 mM | 0.213 mL | 1.0648 mL | 2.1295 mL |
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- Purity: >98.00%
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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