Skip to Content
Merck
All Photos(3)

Documents

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

Sign Into View Organizational & Contract Pricing
All Photos(3)

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’.

Already Own This Product?

Find documentation for the products that you have recently purchased in the Document Library.

Visit the Document Library

Customers Also Viewed

Slide 1 of 6

1 of 6

Reversan ≥98% (HPLC)

Sigma-Aldrich

SML0173

Reversan

Prazosin hydrochloride ≥99.0% (HPLC)

Sigma-Aldrich

P7791

Prazosin hydrochloride

Digoxin analytical standard

Supelco

D6003

Digoxin

Febuxostat 98.5-102.0%

Sigma-Aldrich

SML1285

Febuxostat

Diflunisal analytical standard

Supelco

D3281

Diflunisal

Benzbromarone analytical standard

Supelco

B5774

Benzbromarone

Architecture of chimeric spheroids controls drug transport
Curran S, et al.
Cancer Microenvironment, 8(2), 101-109 (2015)
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)
Makiko Nakamura et al.
Drug metabolism and pharmacokinetics, 33(1), 77-81 (2018-01-18)
Hyperuricemia induces gout and kidney stones and accelerates the progression of renal and cardiovascular diseases. Adenosine 5'-triphosphate-binding cassette subfamily G member 2 (ABCG2) is a urate transporter, and common dysfunctional variants of ABCG2, non-functional Q126X (rs72552713) and semi-functional Q141K (rs2231142)
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
View All Related Papers

Articles

Protein-based Drug Transport

Protein-based drug transporters are found in most tissues including liver, kidney, intestine, and brain. These transporters are particularly important in cancer treatment and multi-drug resistance research. Understanding the specific mechanisms of tumor cell transporters is becoming an essential aspect of chemotherapeutic drug design.

Related Content

Discover Bioactive Small Molecules for ADME/Tox

Discover Bioactive Small Molecules for ADME/Tox

Our team of scientists has experience in all areas of research including Life Science, Material Science, Chemical Synthesis, Chromatography, Analytical and many others.

Contact Technical Service