PD 146176 Chemical Properties

Melting point:

160 °C

Boiling point:

485.4±24.0 °C(Predicted)

Density 

1.333±0.06 g/cm3(Predicted)

storage temp. 

Store at +4°C

solubility 

DMSO: 16 mg/mL, soluble

form 

solid

pka

16.17±0.20(Predicted)

color 

cream-colored

Safety Information

Safety Statements 

22-24/25

WGK Germany 

3

PD 146176 Usage And Synthesis

Description

PD 146176 is a potent and selective inhibitor of reticulocyte 15-lipoxygenase-1. It limits hypercholesterolemia-induced atherosclerosis in New Zealand White rabbits and reduces oxidant stress-induced apoptosis in endothelial cells. PD 146176 inhibits amyloid β protein aggregate formation without changing total levels of amyloid β precursor protein (APP) in cells stably expressing APP. In addition, it lacks significant non-specific antioxidant properties.

Uses

PD 146176 has been used to study its influence on ex vivo leukotriene B4 (LTB4) and lipoxin A4 (LXA4) secretion in adipose tissue.

Definition

ChEBI: PD-146176 is an organic heterotetracyclic compound that is 1H-indole which is ortho-fused to a 2H-1-benzothiopyran group at positions 2-3. It is an inhibitor of 15-lipoxygenase that limits atherosclerotic lesion development in rabbits. It has a role as a ferroptosis inhibitor, an EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor and an antiatherogenic agent. It is an organic heterotetracyclic compound, an organosulfur heterocyclic compound and an organonitrogen heterocyclic compound.

Biological Activity

Specific, non-competitve 15-lipoxygenase (15-LOX) inhibitor (K i = 197nM) that has no demonstrable effect on 5-LOX, 12-LOX, COX-1 or COX-2 (IC 50 = 0.54 μ M for 15-LOX in rabbit reticulocytes). Lacks non-specific antioxidant properties and prevents atherogenesis via regulation of monocyte-macrophage enrichment in vivo .

Biochem/physiol Actions

PD 146176 blocks neuroprotectin D1 (NPD1) and eicosanoid synthesis by inhibiting the 5-lipoxygenase-1 (15-LOX-1) enzyme.

storage

Store at +4°C

References

[1] THOMAS M.A BOCAN . A specific 15-lipoxygenase inhibitor limits the progression and monocyte–macrophage enrichment of hypercholesterolemia-induced atherosclerosis in the rabbit[J]. Atherosclerosis, 1998, 136 2: Pages 203-216. DOI: 10.1016/s0021-9150(97)00204-9
[2] SANDRA M. SENDOBRY. Attenuation of diet-induced atherosclerosis in rabbits with a highly selective 15-lipoxygenase inhibitor lacking significant antioxidant properties[J]. British Journal of Pharmacology, 2009, 120 7: 1199-1206. DOI: 10.1038/sj.bjp.0701007
[3] LORRAINE M. SORDILLO . Enhanced 15-HPETE production during oxidant stress induces apoptosis of endothelial cells[J]. Prostaglandins & other lipid mediators, 2005, 76 1: Pages 19-34. DOI: 10.1016/j.prostaglandins.2004.10.007
[4] FRANCESCA SUCCOL  Domenico P. A role for 12/15 lipoxygenase in the amyloid β precursor protein metabolism[J]. Journal of Neurochemistry, 2007, 103 1: 380-387. DOI: 10.1111/j.1471-4159.2007.04742.x
[5] RON SHAH . Beyond DPPH: Use of Fluorescence-Enabled Inhibited Autoxidation to Predict Oxidative Cell Death Rescue[J]. Cell Chemical Biology, 2019, 26 11: Pages 1594-1607.e7. DOI: 10.1016/j.chembiol.2019.09.007
[6] MARCUS CONRAD  Derek A P. The chemical basis of ferroptosis[J]. Nature chemical biology, 2019, 15 12: 1137-1147. DOI: 10.1038/s41589-019-0408-1

PD 146176(4079-26-9)Related Product Information

• 15(S)-HPEDE
• CDC
• 5,8,11-EICOSATRIYNOIC ACID
• Caffeic acid
• BW B70C
• 15(S)-HEDE
• Esculetin
• REV 5901
• Baicalein
• PD 146176