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Purity: ≥98%
JNJ-42041935 is a novel, potent, competitive, reversible, and selective inhibitor of prolyl hydroxylase PHD with pKi values of 7.91±0.04, 7.29 ±0.05, and 7.65±0.09 for PHD1, PHD2, and PHD3, respectively. The hypoxia-inducible factor (HIF) prolyl hydroxylase (PHD) enzymes represent novel targets for the treatment of anemia, ulcerative colitis, and ischemic and metabolic disease inter alia. JNJ-42041935 is a new pharmacological tool, which can be used to investigate PHD inhibition and demonstrate that PHD inhibitors offer great promise for the treatment of inflammation-induced anemia.
| Targets |
JNJ-42041935 targets hypoxia-inducible factor prolyl hydroxylase (PHD) enzymes (pK(I) = 7.3-7.9) [1]
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| ln Vitro |
The most potent PHD2181–417-fold was JNJ-42041935, which had a pIC50 value of 7.0±0.03. The full-length PHD1, PHD2, and PHD3 enzymes (pKi values of 7.91±0.04, 7.29 ±0.05, and 7.65±0.09, respectively) are also inhibited by JNJ-42041935 [1].
1. JNJ-42041935 acts as a potent inhibitor of PHD enzymes with a pK(I) value ranging from 7.3 to 7.9; it functions as a reversible, selective inhibitor and competes with 2-oxoglutarate for binding to PHD enzymes, demonstrating high specificity for the target enzymes in in vitro enzyme activity assays [1] |
| ln Vivo |
In a pathway-induced cooling model, JNJ-42041935 was utilized to assess the effects of intermittent high-dose (50 μg/kg ip) exogenous erythropoietin hemostatic agent with the circulating inhibitor PHD. The anemia that was produced was successfully corrected by JNJ-42041935 (100 μMol/kg, once day for 14 days), but erythropoietin promotion had no impact. JNJ-42041935 (100 μMol/kg face) was administered for five days in a row. The rise in reticulocytes was twofold, hemoglobin was increased by 2.3 g/dl, and hematocrit increased by 9%. After administering 300 μMol/kg JNJ-42041935 topically, mice's peritoneal bioluminescence increased by 2.2 ± 0.3 times compared to vehicle controls treated with luciferase [1].
1. In a rat model of inflammation-induced anemia, JNJ-42041935 administered at a dose of 100 μmol/kg once daily for 14 days effectively reversed the inflammation-induced anemia; in contrast, intermittent high doses (50 μg/kg via intraperitoneal injection) of an exogenous erythropoietin receptor agonist showed no therapeutic effect on this type of anemia in the same model [1] |
| Enzyme Assay |
1. The inhibitory activity of JNJ-42041935 against PHD enzymes was evaluated through a series of enzyme activity assays: first, the binding affinity of the compound to PHD enzymes was determined by measuring the pK(I) value (7.3-7.9); then, the competitive nature of the inhibition was assessed by investigating the interaction between JNJ-42041935 and 2-oxoglutarate, a key cofactor for PHD enzymes; additionally, the reversibility and selectivity of JNJ-42041935 towards PHD enzymes were verified by comparing its inhibitory effects on PHD with those on other unrelated enzymes, confirming its specific action on the target [1]
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| Animal Protocol |
1. For the inflammation-induced anemia model in rats: JNJ-42041935 was formulated and administered to rats at a dose of 100 μmol/kg once a day for a continuous 14-day period via an unspecified route; a control group was set up, which received an exogenous erythropoietin receptor agonist at a dose of 50 μg/kg via intraperitoneal injection (intermittent high-dose regimen); during the experimental period, hematological parameters related to anemia (such as red blood cell count, hemoglobin concentration, hematocrit) were regularly measured to evaluate the therapeutic effect of JNJ-42041935 on inflammation-induced anemia, and the body weight and general condition of the rats were also monitored to assess the safety of the drug [1]
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| References | |
| Additional Infomation |
1. Hypoxia-inducible factor (HIF) prolyl hydroxylase (PHD) is a novel therapeutic target for treating anemia, ulcerative colitis, ischemic diseases, metabolic diseases, and other diseases [1]. 2. JNJ-42041935 is a novel small molecule PHD inhibitor identified by a structure-based drug design method [1]. 3. JNJ-42041935 can be used as an important pharmacological tool for studying the biological effects of PHD inhibition. Animal experiments have shown that PHD inhibitors have great potential in treating inflammatory anemia [1].
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| Molecular Formula |
C12H6N4O3F3CL
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|---|---|
| Molecular Weight |
346.649
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| Exact Mass |
346.008
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| Elemental Analysis |
C, 41.58; H, 1.74; Cl, 10.23; F, 16.44; N, 16.16; O, 13.85
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| CAS # |
1193383-09-3
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| PubChem CID |
45102710
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| Appearance |
White to off-white solid powder
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| Density |
1.8±0.1 g/cm3
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| Boiling Point |
555.9±60.0 °C at 760 mmHg
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| Flash Point |
290.0±32.9 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.674
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| LogP |
3.72
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
23
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| Complexity |
469
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC(C(C=N1)=CN1C2=NC3=CC(Cl)=C(OC(F)(F)F)C=C3N2)=O
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| InChi Key |
FXHHASJVTYRJHH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H6ClF3N4O3/c13-6-1-7-8(2-9(6)23-12(14,15)16)19-11(18-7)20-4-5(3-17-20)10(21)22/h1-4H,(H,18,19)(H,21,22)
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| Chemical Name |
1-(5-chloro-6-(trifluoromethoxy)-1H-benzo[d]imidazol-2-yl)-1H-pyrazole-4-carboxylic acid
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| Synonyms |
JNJ-42041935; JNJ 42041935; JNJ42041935.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 36 mg/mL (~103.85 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.21 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.21 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8848 mL | 14.4238 mL | 28.8475 mL | |
| 5 mM | 0.5770 mL | 2.8848 mL | 5.7695 mL | |
| 10 mM | 0.2885 mL | 1.4424 mL | 2.8848 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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