Synonym
Pyr6; Pyr-6; Pyr 6
IUPAC/Chemical Name
N-(4-(3,5-Bis(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)-3-fluoroisonicotinamide
InChi Key
XZIQSOZOLJJMFN-UHFFFAOYSA-N
InChi Code
InChI=1S/C17H9F7N4O/c18-12-8-25-6-5-11(12)15(29)26-9-1-3-10(4-2-9)28-14(17(22,23)24)7-13(27-28)16(19,20)21/h1-8H,(H,26,29)
SMILES Code
O=C(NC1=CC=C(N2N=C(C(F)(F)F)C=C2C(F)(F)F)C=C1)C3=CC=NC=C3F
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
Shelf Life
>3 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
2934.99.03.00
Biological target:
Pyr6 blocks SOCE in thapsigargin treated, calcium depleted BRL-2H3 cells (IC50 = 0.49 μM), but has poor activity against carbachol-induced, TRPC3-mediated calcium entry in TRPC3-transfected HEK293 cells (IC50 = 18.46 μM).
In vitro activity:
Pyr6 exhibited a 37-fold higher potency to inhibit Orai1-mediated Ca(2+) entry as compared with TRPC3-mediated Ca(2+) entry and potently suppressed mast cell activation. Pyr6 is able to distinguish between TRPC and Orai-mediated Ca(2+) entry and may serve as useful tools for the analysis of cellular functions of the underlying Ca(2+) channels.
Reference: Br J Pharmacol. 2012 Dec;167(8):1712-22. https://pubmed.ncbi.nlm.nih.gov/22862290/
In vivo activity:
To be determined
Preparing Stock Solutions
The following data is based on the
product
molecular weight
418.27
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. Silva JDPD, Ballejo G. Pharmacological characterization of the calcium influx pathways involved in nitric oxide production by endothelial cells. Einstein (Sao Paulo). 2019 Jun 3;17(3):eAO4600. doi: 10.31744/einstein_journal/2019AO4600. PMID: 31166411; PMCID: PMC6550436.
2. Schleifer H, Doleschal B, Lichtenegger M, Oppenrieder R, Derler I, Frischauf I, Glasnov TN, Kappe CO, Romanin C, Groschner K. Novel pyrazole compounds for pharmacological discrimination between receptor-operated and store-operated Ca(2+) entry pathways. Br J Pharmacol. 2012 Dec;167(8):1712-22. doi: 10.1111/j.1476-5381.2012.02126.x. PMID: 22862290; PMCID: PMC3525873.
In vitro protocol:
1. Silva JDPD, Ballejo G. Pharmacological characterization of the calcium influx pathways involved in nitric oxide production by endothelial cells. Einstein (Sao Paulo). 2019 Jun 3;17(3):eAO4600. doi: 10.31744/einstein_journal/2019AO4600. PMID: 31166411; PMCID: PMC6550436.
2. Schleifer H, Doleschal B, Lichtenegger M, Oppenrieder R, Derler I, Frischauf I, Glasnov TN, Kappe CO, Romanin C, Groschner K. Novel pyrazole compounds for pharmacological discrimination between receptor-operated and store-operated Ca(2+) entry pathways. Br J Pharmacol. 2012 Dec;167(8):1712-22. doi: 10.1111/j.1476-5381.2012.02126.x. PMID: 22862290; PMCID: PMC3525873.
In vivo protocol:
To be determined
1: Chauvet S, Jarvis L, Chevallet M, Shrestha N, Groschner K, Bouron A. Pharmacological Characterization of the Native Store-Operated Calcium Channels of Cortical Neurons from Embryonic Mouse Brain. Front Pharmacol. 2016 Dec 12;7:486. doi: 10.3389/fphar.2016.00486. eCollection 2016. Erratum in: Front Pharmacol. 2017 Mar 22;8:152. PubMed PMID: 28018223; PubMed Central PMCID: PMC5149554.
2: Kim HJ, Woo J, Nam Y, Nam JH, Kim WK. Differential modulation of TWIK-related K(+) channel (TREK) and TWIK-related acid-sensitive K(+) channel 2 (TASK2) activity by pyrazole compounds. Eur J Pharmacol. 2016 Nov 15;791:686-695. doi: 10.1016/j.ejphar.2016.08.030. Epub 2016 Aug 26. PubMed PMID: 27568832.
3: Zuccolo E, Bottino C, Diofano F, Poletto V, Codazzi AC, Mannarino S, Campanelli R, Fois G, Marseglia GL, Guerra G, Montagna D, Laforenza U, Rosti V, Massa M, Moccia F. Constitutive Store-Operated Ca(2+) Entry Leads to Enhanced Nitric Oxide Production and Proliferation in Infantile Hemangioma-Derived Endothelial Colony-Forming Cells. Stem Cells Dev. 2016 Feb 15;25(4):301-19. doi: 10.1089/scd.2015.0240. Epub 2016 Jan 26. PubMed PMID: 26654173.
4: Santiago E, Climent B, Muñoz M, García-Sacristán A, Rivera L, Prieto D. Hydrogen peroxide activates store-operated Ca(2+) entry in coronary arteries. Br J Pharmacol. 2015 Nov;172(22):5318-32. doi: 10.1111/bph.13322. Epub 2015 Oct 24. PubMed PMID: 26478127; PubMed Central PMCID: PMC5341218.
