Synonym
JNJ-42041935; JNJ 42041935; JNJ42041935.
IUPAC/Chemical Name
1-(5-chloro-6-(trifluoromethoxy)-1H-benzo[d]imidazol-2-yl)-1H-pyrazole-4-carboxylic acid
InChi Key
FXHHASJVTYRJHH-UHFFFAOYSA-N
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)
SMILES Code
ClC1=CC2=C(NC(N3C=C(C(O)=O)C=N3)=N2)C=C1OC(F)(F)F
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, not in water
Shelf Life
>2 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
2934.99.9001
Biological target:
JNJ-42041935 is a potent, competitive and selective inhibitor of prolyl hydroxylase PHD; inhibits PHD1, PHD2, and PHD3 with pKi values of 7.91±0.04, 7.29 ±0.05, and 7.65±0.09, respectively.
In vitro activity:
JNJ-42041935 and desferrioxamine were approximately equipotent in the HIF-1α accumulation and erythropoietin secretion assays in Hep3B cells (Table 1). Ciclopirox was 10-fold more potent than JNJ-42041935 in these cell-based assays; however, the response was biphasic (Fig. 5F), and therefore, only the data for the concentration range 1 to 10 μM were analyzed. The data for clioquinol could not be analyzed using nonlinear regression because of the steep concentration-response curves generated (Fig. 5D). The maximal responses for JNJ-42041935, desferrioxamine, and ciclopirox in the HIF-1α accumulation and erythropoietin secretion assays were not significantly different (Table 1). Thus, JNJ-42041935 was a robust tool to elevate HIF-1α and stimulate erythropoietin secretion in Hep3B cells.
Reference: Mol Pharmacol. 2011 Jun;79(6):910-20. https://molpharm.aspetjournals.org/content/79/6/910.long
In vivo activity:
Six hours after administration of test compounds, only JNJ-42041935 stimulated erythropoietin secretion in vivo (Fig. 7A). Thus, plasma erythropoietin was elevated by 55- and 304-fold after oral doses of 100 and 300 μmol/kg JNJ-42041935, respectively. Furthermore, administration of JNJ-42041935 (100 μmol/kg p.o.) for 5 consecutive days resulted in a 2-fold increase in reticulocytes, an increase in hemoglobin by 2.3 g/dl, and an increase in the hematocrit of 9% (Fig. 7, B–D). JNJ-42041935 was the only compound tested that performed well in vivo.
Reference: Mol Pharmacol. 2011 Jun;79(6):910-20. https://molpharm.aspetjournals.org/content/79/6/910.long
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
33.0 |
95.20 |
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
346.65
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. Barrett TD, Palomino HL, Brondstetter TI, Kanelakis KC, Wu X, Haug PV, Yan W, Young A, Hua H, Hart JC, Tran DT, Venkatesan H, Rosen MD, Peltier HM, Sepassi K, Rizzolio MC, Bembenek SD, Mirzadegan T, Rabinowitz MH, Shankley NP. Pharmacological characterization of 1-(5-chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid (JNJ-42041935), a potent and selective hypoxia-inducible factor prolyl hydroxylase inhibitor. Mol Pharmacol. 2011 Jun;79(6):910-20. doi: 10.1124/mol.110.070508. Epub 2011 Mar 3. PMID: 21372172.
In vitro protocol:
1. Barrett TD, Palomino HL, Brondstetter TI, Kanelakis KC, Wu X, Haug PV, Yan W, Young A, Hua H, Hart JC, Tran DT, Venkatesan H, Rosen MD, Peltier HM, Sepassi K, Rizzolio MC, Bembenek SD, Mirzadegan T, Rabinowitz MH, Shankley NP. Pharmacological characterization of 1-(5-chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid (JNJ-42041935), a potent and selective hypoxia-inducible factor prolyl hydroxylase inhibitor. Mol Pharmacol. 2011 Jun;79(6):910-20. doi: 10.1124/mol.110.070508. Epub 2011 Mar 3. PMID: 21372172.
In vivo protocol:
1. Barrett TD, Palomino HL, Brondstetter TI, Kanelakis KC, Wu X, Haug PV, Yan W, Young A, Hua H, Hart JC, Tran DT, Venkatesan H, Rosen MD, Peltier HM, Sepassi K, Rizzolio MC, Bembenek SD, Mirzadegan T, Rabinowitz MH, Shankley NP. Pharmacological characterization of 1-(5-chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid (JNJ-42041935), a potent and selective hypoxia-inducible factor prolyl hydroxylase inhibitor. Mol Pharmacol. 2011 Jun;79(6):910-20. doi: 10.1124/mol.110.070508. Epub 2011 Mar 3. PMID: 21372172.
1: Binó L, Kučera J, Štefková K, Švihálková Šindlerová L, Lánová M, Kudová J,
Kubala L, Pacherník J. The stabilization of hypoxia inducible factor modulates
differentiation status and inhibits the proliferation of mouse embryonic stem
cells. Chem Biol Interact. 2016 Jan 25;244:204-14. doi:
10.1016/j.cbi.2015.12.007. Epub 2015 Dec 23. PubMed PMID: 26723917.
2: Corcoran A, Kunze R, Harney SC, Breier G, Marti HH, O'Connor JJ. A role for
prolyl hydroxylase domain proteins in hippocampal synaptic plasticity.
Hippocampus. 2013 Oct;23(10):861-72. doi: 10.1002/hipo.22142. Epub 2013 Jun 6.
PubMed PMID: 23674383.
3: Barrett TD, Palomino HL, Brondstetter TI, Kanelakis KC, Wu X, Haug PV, Yan W,
Young A, Hua H, Hart JC, Tran DT, Venkatesan H, Rosen MD, Peltier HM, Sepassi K,
Rizzolio MC, Bembenek SD, Mirzadegan T, Rabinowitz MH, Shankley NP.
Pharmacological characterization of
1-(5-chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic
acid (JNJ-42041935), a potent and selective hypoxia-inducible factor prolyl
hydroxylase inhibitor. Mol Pharmacol. 2011 Jun;79(6):910-20. doi:
10.1124/mol.110.070508. Epub 2011 Mar 3. PubMed PMID: 21372172.
4: Kirkham K. American Chemical Society-239th national meeting--Investigating new
therapeutic candidates: part 2. 21-25 March 2010, San Francisco, CA, USA. IDrugs.
2010 May;13(5):292-4. PubMed PMID: 20432181.
