MedKoo Biosciences, Inc.
Tel:   +1-919-636-5577    Fax:   +1-919-980-4831    Email:   sales@medkoo.com
Search
Login Register
Search
MedKoo Cat#: 558226 | Name: Ko-143
Featured New

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Ko-143 is a potent and selective breast cancer resistance protein multidrug transporter (BCRP) inhibitor (EC90 = 26 nM). Ko-143 is a nontoxic analog of fungal toxin fumitremorgin C, is a potent inhibitor of ABCG2.

Chemical Structure

Ko-143
Ko-143
CAS#461054-93-3

Theoretical Analysis

MedKoo Cat#: 558226

Name: Ko-143

CAS#: 461054-93-3

Chemical Formula: C26H35N3O5

Exact Mass: 469.2577

Molecular Weight: 469.58

Elemental Analysis: C, 66.50; H, 7.51; N, 8.95; O, 17.04

Price and Availability

Size Price Availability Quantity
200mg USD 1,950.00 2 Weeks
500mg USD 2,950.00 2 Weeks
1g USD 3,650.00 2 Weeks
2g USD 5,950.00 2 Weeks
Bulk Inquiry
Buy Now
Add to Cart
Related CAS #
No Data
Synonym
Ko-143; Ko-143; Ko-143.
IUPAC/Chemical Name
tert-butyl 3-((3S,6S,12aS)-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
InChi Key
NXNRAECHCJZNRF-JBACZVJFSA-N
InChi Code
InChI=1S/C26H35N3O5/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)/t18-,20-,21-/m0/s1
SMILES Code
O=C(OC(C)(C)C)CC[C@@H]1NC([C@]2([H])CC3=C([C@H](CC(C)C)N2C1=O)NC4=C3C=CC(OC)=C4)=O
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Biological target:
Ko 143 is a potent and selective ATP-binding cassette subfamily G member 2 (ABCG2/BCRP) inhibitor.
In vitro activity:
Elevated levels of ABCG2 in U87 cells grown as tumor spheres or in U251 cells after ABCG2 induction led to a 6-fold lower accumulation of chlorin e6 and the light dose needed to reduce cell viability by 50% (LD50) was 2.5 to 4-fold higher. Both accumulation and PDT response can be restored by KO143, an efficient non-toxic inhibitor of ABCG2. Reference: J Photochem Photobiol B. 2018 Jan;178:182-191. https://pubmed.ncbi.nlm.nih.gov/29156346/
In vivo activity:
TBD
Solvent mg/mL mM
Solubility
DMF 25.0 53.24
DMSO 59.4 126.43
Ethanol 70.5 150.09
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 469.58 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Abdel Gaber SA, Müller P, Zimmermann W, Hüttenberger D, Wittig R, Abdel Kader MH, Stepp H. ABCG2-mediated suppression of chlorin e6 accumulation and photodynamic therapy efficiency in glioblastoma cell lines can be reversed by KO143. J Photochem Photobiol B. 2018 Jan;178:182-191. doi: 10.1016/j.jphotobiol.2017.10.035. Epub 2017 Oct 28. PMID: 29156346.
In vitro protocol:
1. Abdel Gaber SA, Müller P, Zimmermann W, Hüttenberger D, Wittig R, Abdel Kader MH, Stepp H. ABCG2-mediated suppression of chlorin e6 accumulation and photodynamic therapy efficiency in glioblastoma cell lines can be reversed by KO143. J Photochem Photobiol B. 2018 Jan;178:182-191. doi: 10.1016/j.jphotobiol.2017.10.035. Epub 2017 Oct 28. PMID: 29156346.
In vivo protocol:
TBD
1: Li W, Sun H, Zhang X, Wang H, Wu B. Efflux transport of chrysin and apigenin sulfates in HEK293 cells overexpressing SULT1A3: The role of multidrug resistance-associated protein 4 (MRP4/ABCC4). Biochem Pharmacol. 2015 Nov 1;98(1):203-14. doi: 10.1016/j.bcp.2015.08.090. Epub 2015 Aug 17. PubMed PMID: 26291395. 2: Lim HY, Ho QS, Wong KP. Interplay of metabolizing enzymes and transporter of xenobiotics. Xenobiotica. 2016 Jan;46(1):25-33. doi: 10.3109/00498254.2015.1049576. Epub 2015 Jul 30. PubMed PMID: 26226519. 3: Kim JH, Park JM, Roh YJ, Kim IW, Hasan T, Choi MG. Enhanced efficacy of photodynamic therapy by inhibiting ABCG2 in colon cancers. BMC Cancer. 2015 Jul 7;15:504. doi: 10.1186/s12885-015-1514-4. PubMed PMID: 26149077; PubMed Central PMCID: PMC4494642. 4: Weidner LD, Zoghbi SS, Lu S, Shukla S, Ambudkar SV, Pike VW, Mulder J, Gottesman MM, Innis RB, Hall MD. The Inhibitor Ko143 Is Not Specific for ABCG2. J Pharmacol Exp Ther. 2015 Sep;354(3):384-93. doi: 10.1124/jpet.115.225482. Epub 2015 Jul 6. PubMed PMID: 26148857; PubMed Central PMCID: PMC4538874. 5: Dalzell AM, Mistry P, Wright J, Williams FM, Brown CD. Characterization of multidrug transporter-mediated efflux of avermectins in human and mouse neuroblastoma cell lines. Toxicol Lett. 2015 Jun 15;235(3):189-98. doi: 10.1016/j.toxlet.2015.04.005. Epub 2015 Apr 9. PubMed PMID: 25865432. 6: Römermann K, Helmer R, Löscher W. The antiepileptic drug lamotrigine is a substrate of mouse and human breast cancer resistance protein (ABCG2). Neuropharmacology. 2015 Jun;93:7-14. doi: 10.1016/j.neuropharm.2015.01.015. Epub 2015 Jan 31. PubMed PMID: 25645391. 7: Porcelli L, Giovannetti E, Assaraf YG, Jansen G, Scheffer GL, Kathman I, Azzariti A, Paradiso A, Peters GJ. The EGFR pathway regulates BCRP expression in NSCLC cells: role of erlotinib. Curr Drug Targets. 2014;15(14):1322-30. PubMed PMID: 25479544. 8: Jin JO, Zhang W, Wong KW, Kwak M, van Driel IR, Yu Q. Inhibition of breast cancer resistance protein (ABCG2) in human myeloid dendritic cells induces potent tolerogenic functions during LPS stimulation. PLoS One. 2014 Aug 11;9(8):e104753. doi: 10.1371/journal.pone.0104753. eCollection 2014. PubMed PMID: 25111504; PubMed Central PMCID: PMC4128747. 9: Miguel V, Otero JA, García-Villalba R, Tomás-Barberán F, Espín JC, Merino G, Álvarez AI. Role of ABCG2 in transport of the mammalian lignan enterolactone and its secretion into milk in Abcg2 knockout mice. Drug Metab Dispos. 2014 May;42(5):943-6. doi: 10.1124/dmd.113.055970. Epub 2014 Feb 25. PubMed PMID: 24568887. 10: Bakhsheshian J, Wei BR, Chang KE, Shukla S, Ambudkar SV, Simpson RM, Gottesman MM, Hall MD. Bioluminescent imaging of drug efflux at the blood-brain barrier mediated by the transporter ABCG2. Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20801-6. doi: 10.1073/pnas.1312159110. Epub 2013 Dec 2. PubMed PMID: 24297888; PubMed Central PMCID: PMC3870704. 11: Issa ME, Hall SR, Dupuis SN, Graham CL, Jakeman DL, Goralski KB. Jadomycins are cytotoxic to ABCB1-, ABCC1-, and ABCG2-overexpressing MCF7 breast cancer cells. Anticancer Drugs. 2014 Mar;25(3):255-69. doi: 10.1097/CAD.0000000000000043. PubMed PMID: 24231527. 12: Tang L, Li Y, Chen WY, Zeng S, Dong LN, Peng XJ, Jiang W, Hu M, Liu ZQ. Breast cancer resistance protein-mediated efflux of luteolin glucuronides in HeLa cells overexpressing UDP-glucuronosyltransferase 1A9. Pharm Res. 2014 Apr;31(4):847-60. doi: 10.1007/s11095-013-1207-0. Epub 2013 Oct 3. PubMed PMID: 24092055. 13: Barron GA, Moseley H, Woods JA. Differential sensitivity in cell lines to photodynamic therapy in combination with ABCG2 inhibition. J Photochem Photobiol B. 2013 Sep 5;126:87-96. doi: 10.1016/j.jphotobiol.2013.07.003. Epub 2013 Jul 10. PubMed PMID: 23911860. 14: Matsuda Y, Konno Y, Hashimoto T, Nagai M, Taguchi T, Satsukawa M, Yamashita S. In vivo assessment of the impact of efflux transporter on oral drug absorption using portal vein-cannulated rats. Drug Metab Dispos. 2013 Aug;41(8):1514-21. doi: 10.1124/dmd.113.051680. Epub 2013 May 16. PubMed PMID: 23686319. 15: Schymeinsky J, Mayer H, Tomsic C, Tilp C, Schuetz JD, Cui Y, Wollin L, Gantner F, Erb KJ. The absence of mrp4 has no effect on the recruitment of neutrophils and eosinophils into the lung after LPS, cigarette smoke or allergen challenge. PLoS One. 2013 Apr 22;8(4):e61193. doi: 10.1371/journal.pone.0061193. Print 2013. PubMed PMID: 23613808; PubMed Central PMCID: PMC3632556. 16: Lovasz N, Ducza E, Zupko I, Falkay G. Increase of the uterus-relaxant effect of nifedipine by the Abcg2 efflux protein inhibitor KO134 in the rat in vivo. In Vivo. 2013 May-Jun;27(3):363-9. PubMed PMID: 23606692. 17: González-Sarrías A, Miguel V, Merino G, Lucas R, Morales JC, Tomás-Barberán F, Alvarez AI, Espín JC. The gut microbiota ellagic acid-derived metabolite urolithin A and its sulfate conjugate are substrates for the drug efflux transporter breast cancer resistance protein (ABCG2/BCRP). J Agric Food Chem. 2013 May 8;61(18):4352-9. doi: 10.1021/jf4007505. Epub 2013 Apr 24. PubMed PMID: 23586460. 18: Zhang D, He K, Herbst JJ, Kolb J, Shou W, Wang L, Balimane PV, Han YH, Gan J, Frost CE, Humphreys WG. Characterization of efflux transporters involved in distribution and disposition of apixaban. Drug Metab Dispos. 2013 Apr;41(4):827-35. doi: 10.1124/dmd.112.050260. Epub 2013 Feb 4. PubMed PMID: 23382458. 19: Rong Z, Xu Y, Zhang C, Xiang D, Li X, Liu D. Evaluation of intestinal absorption of amtolmetin guacyl in rats: breast cancer resistant protein as a primary barrier of oral bioavailability. Life Sci. 2013 Feb 27;92(3):245-51. doi: 10.1016/j.lfs.2012.12.010. Epub 2013 Jan 16. PubMed PMID: 23333829. 20: Zander SA, Beijnen JH, van Tellingen O. Sensitive method for plasma and tumor Ko143 quantification using reversed-phase high-performance liquid chromatography and fluorescence detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Jan 15;913-914:129-36. doi: 10.1016/j.jchromb.2012.11.003. Epub 2012 Dec 6. PubMed PMID: 23291288.