Ko 143

SKU: orb1296146

Description

Ko 143 is a potent and selective small molecule inhibitor of the ABCG2/BCRP transporter. This compound is widely used in pharmacological research to study drug efflux, bioavailability, and multidrug resistance in both cellular and animal models.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 461054-93-3
• MW: 469.57
• Purity: 99.89% (May vary between batches)
• Formula: C₂₆H₃₅N₃O₅
• SMILES: COc1ccc2c3C[C@@H]4N([C@@H](CC(C)C)c3[nH]c2c1)C(=O)[C@H](CCC(=O)OC(C)(C)C)NC4=O
• Target: ABC Transporter,BCRP
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (7.03 mM);DMSO:90 mg/mL (191.66 mM);H2O:Insoluble

Bioactivity

• Target IC50:
  ABCG2:26 nM (EC50)
• In Vivo:
  Ko143 (10 mg/kg, p.o.) increases the oral availability of SKF 104864A in mice .
• In Vitro:
  In HEK G2 cells and mouse G2 cells, Ko143 (10 nM) significantly decreases the IC50 of MTX. Ko143 (1-100 μM) metabolite does not inhibit the function of ABC transporters . Reversal of drug resistance in SKF 104864A-selected mouse MEF3.8/T6400 cells and human IGROV1/T8 cells by Ko143 . Ko143 inhibits BCRP-mediated transport of ZD 4522 in Madin-Darby Canine Kidney (MDCK) 2-BCRP421CC (wild type) cells and MDCK2-BCRP421AA (mutant type) cells .
• Cell Research:
  Cells are plated at 400 or 1000/well in 96-well plates the night before the addition of drugs. A concentration series of the drug is applied along one plate axis and left for the duration of the assay. Plates are harvested after 4-5 days while untreated wells are still subconfluent. Relative cell proliferation is quantified with CyQuant or Sybr Green I fluorescent nucleic acid stains. Assays with human cell lines are performed in the presence of 0.1 μm PSC833 to inhibit confounding P-gp activity .
• Animal Research:
  Oral toxicity of FTC analogs in mice is tested by mixing 50 mg/mL stocks in DMSO 1:1 with Tween 80 (polyoxyethylene sorbitan mono-oleate) and diluting with 5% w/v glucose such that the final volume administered by oral gavage is 10 μL/g of body weight. Pairs of mice are administered oral doses of 50 mg/kg Ko132, Ko134, Ko143, or vehicle under light methoxyflurane anesthesia. Final tests of 50 mg/kg Ko134 or Ko143 are performed on additional pairs of unanesthetized animals to observe any behavioral effects. Further, another pair of mice receive a higher dose of 100 mg/kg Ko134. For i.p. toxicity tests, the FTC analog stocks in DMSO are dispersed in at least 10 volumes of sterile corn oil such that the injected volume is 5 μL/g of body weight. After pilot tests at lower doses show no adverse effects, mice (4 per group) are administered vehicle or 10 mg/kg i.p. of Ko132, Ko134, or Ko143. The mice are observed continuously during the first hour after administration and then at increasing intervals for 2 weeks, after which they are sacrificed for histological examination of major organs and structures .

Storage & Handling

• Storage: store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Breast cancer resistance protein, BCRP, ABCG2, Ko 143, Ko143, Ko-143, inhibit, Inhibitor

Compound Identifiers

PubChem CID

10322450