JNJ-42041935
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MedKoo CAT#: 522678

CAS#: 1193383-09-3

Description: JNJ-42041935 is a potent (pK(I) = 7.3-7.9), 2-oxoglutarate competitive, reversible, and selective inhibitor of PHD enzymes. 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. 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.


Chemical Structure

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JNJ-42041935
CAS# 1193383-09-3

Theoretical Analysis

MedKoo Cat#: 522678
Name: JNJ-42041935
CAS#: 1193383-09-3
Chemical Formula: C12H6ClF3N4O3
Exact Mass: 346.0081
Molecular Weight: 346.6502
Elemental Analysis: C, 41.58; H, 1.74; Cl, 10.23; F, 16.44; N, 16.16; O, 13.85

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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

Appearance: Solid powder

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

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 33.0 95.2

Preparing Stock Solutions

The following data is based on the product molecular weight 346.6502 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.

Recalculate based on batch purity %
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.

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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.