IOX4, PHD2 Inhibitor

IOX4 is a potent and selective PHD2 inhibitor with IC50 ~1.6 nM. It inhibits PHD2 via binding to the 2OG binding site, displays >1, 000-fold selectivity for PHD2 over other 2OG-dependent dioxygenases, including JMJD isoforms, FBXL11, JARID1C, BBOX1, FIH, and FTO. IOX4 is active in vivo, inhibiting prolyl hydroxylation and increasing HIF-1α levels in cells (IC50 ~5.6-11.7 µM) and inducing HIF-1α and HIF-2α expression in mice. The induction of HIF expression in mice occurs in the brain as well as in the liver, kidney, and heart, indicating that IOX4 penetrates the blood-brain barrier. IOX4 could be a useful tool compound for studies aimed at validating the upregulation of HIF for treatment of cerebral diseases including stroke.

Product information

CAS Number: 1154097-71-8

Molecular Weight: 328.33

Formula: C15H16N6O3

Chemical Name: tert-butyl 6-(5-oxo-4-(1H-1,2,3-triazol-1-yl)-2,5-dihydro-1H-pyrazol-1-yl)nicotinate

Smiles: CC(C)(C)OC(=O)C1=CN=C(C=C1)N1NC=C(C1=O)N1C=CN=N1

InChiKey: HWQQDVNGHZIALS-UHFFFAOYSA-N

InChi: InChI=1S/C15H16N6O3/c1-15(2,3)24-14(23)10-4-5-12(16-8-10)21-13(22)11(9-18-21)20-7-6-17-19-20/h4-9,18H,1-3H3

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 100 mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

IOX4 was used at 10-50 µM final concentration in vitro and in cellular assays.

In Vivo:

IOX4 was dosed to mice by IP injection at 17.5-70 mg/kg.

References:

1. Chan MC, et al. Potent and Selective Triazole-Based Inhibitors of the Hypoxia-Inducible Factor Prolyl-Hydroxylases with Activity in the Murine Brain. (2015) PLoS One. 10(7):e0132004.

Products are for research use only. Not for human use.

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