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K2144

Sigma-Aldrich

Ko143 hydrate

≥98% (HPLC), powder, BCRP inhibitor

Synonym(s):

(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 hydrate, Ko-143 hydrate

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About This Item

Empirical Formula (Hill Notation):
C26H35N3O5 · xH2O
CAS Number:
461054-93-3
Molecular Weight:
469.57 (anhydrous basis)
MDL number:
MFCD19053160
UNSPSC Code:
12352200
PubChem Substance ID:
329817134
NACRES:
NA.77

product name

Ko143 hydrate, ≥98% (HPLC)

Quality Level

100

Assay

≥98% (HPLC)

form

powder

color

white to off-white

solubility

DMSO: >10 mg/mL

originator

GlaxoSmithKline

storage temp.

room temp

SMILES string

O.COc1ccc2c3C[C@@H]4N([C@@H](CC(C)C)c3[nH]c2c1)C(=O)[C@H](CCC(=O)OC(C)(C)C)NC4=O

InChI

1S/C26H35N3O5.H2O/c1-14(2)11-20-23-17(16-8-7-15(33-6)12-19(16)27-23)13-21-24(31)28-18(25(32)29(20)21)9-10-22(30)34-26(3,4)5;/h7-8,12,14,18,20-21,27H,9-11,13H2,1-6H3,(H,28,31);1H2/t18-,20-,21-;/m0./s1

InChI key

ZXXZDXPNJJZRDC-PSLBYKFTSA-N

Application

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

Biochem/physiol Actions

Ko143 has been used as a positive control inhibitor on functions of BCRP in MCF7 and BCRP over-expressing MCF7/MX100 cell lines using a BCRP prototypical substrate mitoxantrone. The ABCG2 transporter breast cancer resistance protein (BCRP) plays an important role in disposition of many drugs and environmental toxins. Ko143 displays > 200-fold selectivity over P-gp and MRP-1 transporters. It increases intracellular drug accumulation and reverse BCRP-mediated multidrug resistance. It blocked topotecan and ABZSO transport in a concentration-dependent manner. Ko143 is reported to be a more specific inhibitor of BCRP than other known inhibitors of BCRP such as fumitremorgin C and GF120918.
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.

Features and Benefits

This compound is a featured product for ADME Tox research. Click here to discover more featured ADME Tox products. Learn more about bioactive small molecules for other areas of research at sigma.com/discover-bsm.
This compound was developed by GlaxoSmithKline. To browse the list of other pharma-developed compounds and Approved Drugs/Drug Candidates, click here.

Pictograms

Exclamation mark
GHS07

Signal Word

Warning

Hazard Statements

H315,H319,H335

Hazard Classifications

Eye Irrit. 2 - Skin Irrit. 2 - STOT SE 3

Target Organs

Respiratory system

WGK

WGK 3

Flash Point(F)

Not applicable

Flash Point(C)

Not applicable

Certificates of Analysis (COA)

Search for Certificates of Analysis (COA) by entering the products Lot/Batch Number. Lot and Batch Numbers can be found on a product’s label following the words ‘Lot’ or ‘Batch’.

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Multi-drug resistance ABC transporter inhibition enhances murine ventral prostate stem/progenitor cell differentiation
Samant MD, et al.
Stem Cells and Development, 24(10), 1236-1251 (2015)
Jae Guen Song et al.
Cancer chemotherapy and pharmacology, 78(4), 735-744 (2016-08-16)
The present study aimed to discover a new potent BCRP inhibitor overcoming multidrug resistance. Effects of LW6 on the functional activity and gene expression of two major efflux transporters, BCRP and P-gp, were evaluated by using MDCKII cells overexpressing each
Overcoming resistance to the THZ series of covalent transcriptional CDK inhibitors
Gao Y, et al.
Cell Chemical Biology, 25(2), 135-142 (2018)
Cong Duan et al.
Biopharmaceutics & drug disposition, 38(1), 75-83 (2016-12-08)
Lindera aggregata (Sims) Kosterm root has been used in traditional Chinese medicine for the treatment of rheumatism palsy, dyspepsia and frequent urination for a long time. Norisoboldine, the main active constituent of this herb drug, possesses outstanding anti-arthritis activity. However
Lu Xiao et al.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 93, 456-467 (2016-09-03)
Efflux transporters are extensively distributed and expressed in the intestinal epithelium and contribute to the low oral bioavailability of flavonoids and flavonoid glucuronides by pumping these compounds back into intestinal lumen. Our previous study has shown the inhibitory effect of
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