PMX464 | CAS#485842-97-5 | anti-trypanosomal inhibitor

MedKoo Cat#: 563247 | Name: PMX464

Description:

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

PMX464 is a cytocidal anti-trypanosomal inhibitor that acts by targeting trypanothione metabolism. It is also a putative inhibitor of the thioredoxin-thioredoxin reductase (Trx-TrxR) system.

Chemical Structure

PMX464

CAS#485842-97-5

Theoretical Analysis

MedKoo Cat#: 563247

Name: PMX464

CAS#: 485842-97-5

Chemical Formula: C13H9NO2S

Exact Mass: 243.0354

Molecular Weight: 243.28

Elemental Analysis: C, 64.18; H, 3.73; N, 5.76; O, 13.15; S, 13.18

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Synonym

PMX464; PMX-464; PMX 464;

IUPAC/Chemical Name

4-(2-Benzothiazolyl)-4-hydroxy-2,5-cyclohexadien-1-one

InChi Key

SDYBYKXWYDVVKP-UHFFFAOYSA-N

InChi Code

InChI=1S/C13H9NO2S/c15-9-5-7-13(16,8-6-9)12-14-10-3-1-2-4-11(10)17-12/h1-8,16H

SMILES Code

O=C1C=CC(O)(C2=NC3=CC=CC=C3S2)C=C1

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

Shelf Life

>3 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

2934.99.03.00

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

PMX464 (AW 464), a thiol-reactive quinol, is the inhibitor of thioredoxin-thioredoxin reductase (Trx/TrxR) system.

In vitro activity:

Intercellular adhesion molecule-1 (ICAM-1), granulocyte-macrophage colony-stimulating factor (GM-CSF) and CXCL8, NF-kappaB DNA binding, nuclear translocation of NF-kappaB p65 subunit, IkappaBalpha degradation, IkappaB phosphorylation and IkappaB kinase (IKK) activity were assessed in A549 cells stimulated with IL-1beta with or without PMX464 pretreatment. Effects of PMX464 on ICAM-1 expression in human lung microvascular endothelial cells (HLMVEC) were also investigated. PMX464 reduced ICAM-1, GM-CSF and CXCL8 expression in IL-1beta-stimulated A549 cells and ICAM-1 in HLMVEC. PMX464 inhibited IL-1beta-induced NF-kappaB DNA binding, nuclear translocation of NF-kappaB p65 subunit and factors involved in NF-kappaB activation; specifically, IkappaBalpha degradation, IkappaB phosphorylation and IkappaB kinase (IKK) activity in A549. Reference: Br J Pharmacol. 2008 Nov;155(5):661-72. https://pubmed.ncbi.nlm.nih.gov/18587424/

In vivo activity:

TBD

	Solvent	mg/mL	mM
Solubility
	DMSO	24.3	100.00
	Ethanol	24.3	100.00

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 243.28 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.

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. Callister ME, Pinhu L, Catley MC, Westwell AD, Newton R, Leaver SK, Quinlan GJ, Evans TW, Griffiths MJ, Burke-Gaffney A. PMX464, a thiol-reactive quinol and putative thioredoxin inhibitor, inhibits NF-kappaB-dependent proinflammatory activation of alveolar epithelial cells. Br J Pharmacol. 2008 Nov;155(5):661-72. doi: 10.1038/bjp.2008.258. Epub 2008 Jun 30. PMID: 18587424; PMCID: PMC2442904. 2. Mukherjee A, Huber K, Evans H, Lakhani N, Martin S. A cellular and molecular investigation of the action of PMX464, a putative thioredoxin inhibitor, in normal and colorectal cancer cell lines. Br J Pharmacol. 2007 Aug;151(8):1167-75. doi: 10.1038/sj.bjp.0707342. Epub 2007 Jun 18. PMID: 17572693; PMCID: PMC2189840.

In vitro protocol:

In vivo protocol:

TBD

1: Metcalfe C, Ramasubramoni A, Pula G, Harper MT, Mundell SJ, Coxon CH. Thioredoxin Inhibitors Attenuate Platelet Function and Thrombus Formation. PLoS One. 2016 Oct 7;11(10):e0163006. doi: 10.1371/journal.pone.0163006. PMID: 27716777; PMCID: PMC5055343. 2: König J, Wyllie S, Wells G, Stevens MF, Wyatt PG, Fairlamb AH. Antitumor quinol PMX464 is a cytocidal anti-trypanosomal inhibitor targeting trypanothione metabolism. J Biol Chem. 2011 Mar 11;286(10):8523-8533. doi: 10.1074/jbc.M110.214833. Epub 2011 Jan 6. PMID: 21212280; PMCID: PMC3048735. 3: Hall G, Bradshaw TD, Laughton CA, Stevens MF, Emsley J. Structure of Mycobacterium tuberculosis thioredoxin in complex with quinol inhibitor PMX464. Protein Sci. 2011 Jan;20(1):210-5. doi: 10.1002/pro.533. PMID: 20981751; PMCID: PMC3047077. 4: Wong DP, Wells G, Hagen T. Heteroaromatic 4-arylquinols are novel inducers of nuclear factor-erythroid 2-related factor 2 (Nrf2). Eur J Pharmacol. 2010 Sep 25;643(2-3):188-94. doi: 10.1016/j.ejphar.2010.06.040. Epub 2010 Jun 30. PMID: 20599909. 5: Mukherjee A, Martin SG. The thioredoxin system: a key target in tumour and endothelial cells. Br J Radiol. 2008 Oct;81 Spec No 1:S57-68. doi: 10.1259/bjr/34180435. PMID: 18819999. 6: Sexton DW. Targeting airway inflammation: PMX464 and the epithelial bulls eye. Br J Pharmacol. 2008 Nov;155(5):620-2. doi: 10.1038/bjp.2008.290. Epub 2008 Jul 7. PMID: 18604227; PMCID: PMC2584922. 7: Callister ME, Pinhu L, Catley MC, Westwell AD, Newton R, Leaver SK, Quinlan GJ, Evans TW, Griffiths MJ, Burke-Gaffney A. PMX464, a thiol-reactive quinol and putative thioredoxin inhibitor, inhibits NF-kappaB-dependent proinflammatory activation of alveolar epithelial cells. Br J Pharmacol. 2008 Nov;155(5):661-72. doi: 10.1038/bjp.2008.258. Epub 2008 Jun 30. PMID: 18587424; PMCID: PMC2442904. 8: Mukherjee A, Huber K, Evans H, Lakhani N, Martin S. A cellular and molecular investigation of the action of PMX464, a putative thioredoxin inhibitor, in normal and colorectal cancer cell lines. Br J Pharmacol. 2007 Aug;151(8):1167-75. doi: 10.1038/sj.bjp.0707342. Epub 2007 Jun 18. PMID: 17572693; PMCID: PMC2189840. 9: Matsuura T, Harrison RA, Westwell AD, Nakamura H, Martynyuk AE, Sumners C. Basal and angiotensin II-inhibited neuronal delayed-rectifier K+ current are regulated by thioredoxin. Am J Physiol Cell Physiol. 2007 Jul;293(1):C211-7. doi: 10.1152/ajpcell.00615.2006. Epub 2007 Mar 14. PMID: 17360810. 10: Lion CJ, Matthews CS, Wells G, Bradshaw TD, Stevens MF, Westwell AD. Antitumour properties of fluorinated benzothiazole-substituted hydroxycyclohexa-2,5-dienones ('quinols'). Bioorg Med Chem Lett. 2006 Oct 1;16(19):5005-8. doi: 10.1016/j.bmcl.2006.07.072. PMID: 16908135.