| Name | JNJ-42041935 |
| Description | JNJ-42041935 (HIF-PHD Inhibitor II) is a potent (pKi = 7.3-7.9), 2-oxoglutarate competitive, reversible, and selective inhibitor of PHD enzymes. |
| Kinase Assay | The potency of JNJ-42041935 for inhibition of the structurally related enzyme FIH is assessed by methods similar to those described for PHD2. In brief, activity of FIH is determined using purified glutathione transferase-tagged full-length FIH amino acids 1 to 350 and a synthetic HIF-1α peptide corresponding to residues Asp788 to Leu822. Compounds are preincubated with 17.1 nM FIH for 30 min, followed by a 10-min incubation with 1 μM [2-14C]2-oxoglutarate, in the presence of 10 μM FeNH4SO4 in reaction buffer. The selectivity of JNJ-42041935 for inhibition of a range of other targets available for testing in commercial assays is also assessed at concentrations of 1 and 10 μM[1]. |
| In vitro | JNJ-42041935 is the most potent inhibitor of PHD2181–417 with a pIC50 value of 7.0±0.03. JNJ-42041935 also inhibits full-length PHD1, PHD2, and PHD3 enzymes (pKi values 7.91±0.04, 7.29 ±0.05, and 7.65±0.09, respectively) [1]. |
| In vivo | JNJ-42041935 has been evaluated for its capability to selectively inhibit prolyl hydroxylase domain (PHD) enzymes compared to the effect of intermittent, high doses (50 μg/kg i.p.) of an erythropoietin receptor agonist in a rat model of inflammation-induced anemia. The study demonstrates that JNJ-42041935, administered at a dose of 100 µmol/kg orally once daily for 14 days, successfully ameliorates inflammation-induced anemia, whereas erythropoietin shows no efficacy. Further, a 5-day consecutive oral administration of JNJ-42041935 at 100 µmol/kg led to a doubling in reticulocyte count, a 2.3 g/dl increase in hemoglobin levels, and a 9% rise in hematocrit values. Additionally, a single oral dose of 300 µmol/kg of JNJ-42041935 resulted in a 2.2 ± 0.3-fold increase in peritoneal bioluminescence, relative to luciferase-treated vehicle controls in mice, indicating enhanced activity two hours post-administration [1]. |
| Storage | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | DMSO : 50 mg/mL (144.24 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (5.77 mM), Sonication is recommended.
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| Keywords | PHD3 | PHD2 | PHD1 | JNJ-42041935 | JNJ42041935 | JNJ 42041935 | Inhibitor | inhibit | Hypoxia-inducible factors | HIFs | HIFProlylHydroxylase | HIF-PH | HIF/HIFProlylHydroxylase | HIF/HIF Prolyl-Hydroxylase | HIF/HIF ProlylHydroxylase | HIF Prolyl-Hydroxylase | HIF ProlylHydroxylase | HIF |
| Inhibitors Related | Deferoxamine Mesylate | Hydralazine hydrochloride | Chlorogenic Acid | Roxadustat | Glucosamine | Hydroxycitric acid tripotassium hydrate | Glucosamine hydrochloride | Chloramphenicol | Oroxylin A | Acriflavine Hydrochloride | Albendazole | Glucosamine sulfate |
| Related Compound Libraries | Glycometabolism Compound Library | Bioactive Compound Library | Glutamine Metabolism Compound Library | Angiogenesis related Compound Library | Inhibitor Library | NO PAINS Compound Library | Metabolism Compound Library | Anti-Aging Compound Library | Immunology/Inflammation Compound Library | Bioactive Compounds Library Max | Fluorochemical Library | Transcription Factor-Targeted Compound Library |
United States
