Pyr3 | CAS#1160514-60-2 | TRPC3 antagonist

MedKoo Cat#: 563460 | Name: Pyr3

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Pyr3 is a selective antagonist of the canonical transient receptor potential channel 3 (TRPC3).

Chemical Structure

Pyr3

CAS#1160514-60-2

Theoretical Analysis

MedKoo Cat#: 563460

Name: Pyr3

CAS#: 1160514-60-2

Chemical Formula: C16H11Cl3F3N3O3

Exact Mass: 454.9818

Molecular Weight: 456.62

Elemental Analysis: C, 42.09; H, 2.43; Cl, 23.29; F, 12.48; N, 9.20; O, 10.51

Price and Availability

Size	Price	Availability	Quantity
1mg	USD 210.00
5mg	USD 380.00
10mg	USD 560.00

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Related CAS #

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Synonym

Pyr3; Pyr-3; Pyr 3;

IUPAC/Chemical Name

ethyl 1-(4-(2,3,3-trichloroacrylamido)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

InChi Key

RZHGONNSASQOAY-UHFFFAOYSA-N

InChi Code

InChI=1S/C16H11Cl3F3N3O3/c1-2-28-15(27)10-7-23-25(12(10)16(20,21)22)9-5-3-8(4-6-9)24-14(26)11(17)13(18)19/h3-7H,2H2,1H3,(H,24,26)

SMILES Code

O=C(C1=C(C(F)(F)F)N(C2=CC=C(NC(/C(Cl)=C(Cl)/Cl)=O)C=C2)N=C1)OCC

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

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

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Pyr3 inhibits TRPC3-mediated Ca2+ influx with an IC50 value of 0.7 μM without effect on other TRPC members. Pyr3 suppresses the activation of nuclear factor of activated T cells with an IC50 value of 0.05 μM. Pyr3 has been shown to suppress cardiac hypertrophy in mice.

In vitro activity:

Pyr3 enhances dexamethasone sensitivity in acute lymphoblastic leukemia (ALL) cells through the distraction of Dex-mediated Ca(2+) signaling. Pyr3 alone induced Ca(2+) signaling via only endoplasmic reticulum-released Ca(2+) and exerted inhibitory effect on store-operated Ca(2+) entry in dose-dependent manner in ALL cell lines. Pre-incubation of cells with Pyr3 significantly curtailed the thapsigargin- and Dex-evoked Ca(2+) signaling in ALL cell lines. Reference: Eur J Pharmacol. 2016 Aug 5;784:90-8. https://pubmed.ncbi.nlm.nih.gov/27179991/

In vivo activity:

In a myocardial ischemia/reperfusion (I/R) injury murine model, Pyr3 reduced the myocardial cell apoptosis rate and inflammatory response. Pyr3 may directly bind to TRPC3 channel protein, inhibit TRPC3 channel activity, and improve TRPC3-related myocardial I/R injury. Pyr3 may be used for clarification of TRPC3 functions and for treatments of TRPC3-mediated diseases. Reference: Curr Med Sci. 2020 Dec;40(6):1107-1113. https://pubmed.ncbi.nlm.nih.gov/33428139/

	Solvent	mg/mL	mM
Solubility
	DMF	50.0	109.50
	DMSO	20.0	43.80
	Ethanol	10.0	21.90

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 456.62 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. Abdoul-Azize S, Buquet C, Vannier JP, Dubus I. Pyr3, a TRPC3 channel blocker, potentiates dexamethasone sensitivity and apoptosis in acute lymphoblastic leukemia cells by disturbing Ca(2+) signaling, mitochondrial membrane potential changes and reactive oxygen species production. Eur J Pharmacol. 2016 Aug 5;784:90-8. doi: 10.1016/j.ejphar.2016.05.014. Epub 2016 May 12. PMID: 27179991. 2. Chang HH, Cheng YC, Tsai WC, Tsao MJ, Chen Y. Pyr3 Induces Apoptosis and Inhibits Migration in Human Glioblastoma Cells. Cell Physiol Biochem. 2018;48(4):1694-1702. doi: 10.1159/000492293. Epub 2018 Aug 3. PMID: 30078005. 3. Lu M, Fang XX, Shi DD, Liu R, Ding Y, Zhang QF, Wang HQ, Tang JM, He XJ. A Selective TRPC3 Inhibitor Pyr3 Attenuates Myocardial Ischemia/Reperfusion Injury in Mice. Curr Med Sci. 2020 Dec;40(6):1107-1113. doi: 10.1007/s11596-020-2293-y. Epub 2021 Jan 11. PMID: 33428139. 4. Munakata M, Shirakawa H, Nagayasu K, Miyanohara J, Miyake T, Nakagawa T, Katsuki H, Kaneko S. Transient receptor potential canonical 3 inhibitor Pyr3 improves outcomes and attenuates astrogliosis after intracerebral hemorrhage in mice. Stroke. 2013 Jul;44(7):1981-7. doi: 10.1161/STROKEAHA.113.679332. Epub 2013 May 14. PMID: 23674527.

In vitro protocol:

In vivo protocol:

1. Lu M, Fang XX, Shi DD, Liu R, Ding Y, Zhang QF, Wang HQ, Tang JM, He XJ. A Selective TRPC3 Inhibitor Pyr3 Attenuates Myocardial Ischemia/Reperfusion Injury in Mice. Curr Med Sci. 2020 Dec;40(6):1107-1113. doi: 10.1007/s11596-020-2293-y. Epub 2021 Jan 11. PMID: 33428139. 2. Munakata M, Shirakawa H, Nagayasu K, Miyanohara J, Miyake T, Nakagawa T, Katsuki H, Kaneko S. Transient receptor potential canonical 3 inhibitor Pyr3 improves outcomes and attenuates astrogliosis after intracerebral hemorrhage in mice. Stroke. 2013 Jul;44(7):1981-7. doi: 10.1161/STROKEAHA.113.679332. Epub 2013 May 14. PMID: 23674527.

1: Maltaneri RE, Schiappacasse A, Chamorro ME, Nesse AB, Vittori DC. Participation of membrane calcium channels in erythropoietin-induced endothelial cell migration. Eur J Cell Biol. 2018 Jun 19. pii: S0171-9335(18)30036-0. doi: 10.1016/j.ejcb.2018.06.002. [Epub ahead of print] PubMed PMID: 29945737. 2: Nishida M, Kuwahara K, Kozai D, Sakaguchi R, Mori Y. TRP Channels: Their Function and Potentiality as Drug Targets. In: Nakao K, Minato N, Uemoto S, editors. Innovative Medicine: Basic Research and Development [Internet]. Tokyo: Springer; 2015. Available from http://www.ncbi.nlm.nih.gov/books/NBK500333/ PubMed PMID: 29787169. 3: Sun D, Ma H, Ma J, Wang J, Deng X, Hu C, Deng X. Canonical Transient Receptor Potential Channel 3 Contributes to Febrile Seizure Inducing Neuronal Cell Death and Neuroinflammation. Cell Mol Neurobiol. 2018 Aug;38(6):1215-1226. doi: 10.1007/s10571-018-0586-5. Epub 2018 May 10. PubMed PMID: 29748835. 4: Luo X, Xue L, Xu H, Zhao QY, Wang Q, She YS, Zang DA, Shen J, Peng YB, Zhao P, Yu MF, Chen W, Ma LQ, Chen S, Chen S, Fu X, Hu S, Nie X, Shen C, Zou C, Qin G, Dai J, Ji G, Su Y, Hu S, Chen J, Liu QH. Polygonum aviculare L. extract and quercetin attenuate contraction in airway smooth muscle. Sci Rep. 2018 Feb 15;8(1):3114. doi: 10.1038/s41598-018-20409-x. PubMed PMID: 29449621; PubMed Central PMCID: PMC5814568. 5: Chiu CD, Yao NW, Guo JH, Shen CC, Lee HT, Chiu YP, Ji HR, Chen X, Chen CC, Chang C. Inhibition of astrocytic activity alleviates sequela in acute stages of intracerebral hemorrhage. Oncotarget. 2017 Oct 24;8(55):94850-94861. doi: 10.18632/oncotarget.22022. eCollection 2017 Nov 7. PubMed PMID: 29212271; PubMed Central PMCID: PMC5706917. 6: Goldspink DA, Lu VB, Billing LJ, Larraufie P, Tolhurst G, Gribble FM, Reimann F. Mechanistic insights into the detection of free fatty and bile acids by ileal glucagon-like peptide-1 secreting cells. Mol Metab. 2018 Jan;7:90-101. doi: 10.1016/j.molmet.2017.11.005. Epub 2017 Nov 11. PubMed PMID: 29167062; PubMed Central PMCID: PMC5784317. 7: Otsuka N, Harayama H. Characterization of extracellular Ca(2+) -dependent full-type hyperactivation in ejaculated boar spermatozoa preincubated with a cAMP analog. Mol Reprod Dev. 2017 Nov;84(11):1203-1217. doi: 10.1002/mrd.22921. Epub 2017 Nov 6. PubMed PMID: 28981180. 8: Wang B, Xiong S, Lin S, Xia W, Li Q, Zhao Z, Wei X, Lu Z, Wei X, Gao P, Liu D, Zhu Z. Enhanced Mitochondrial Transient Receptor Potential Channel, Canonical Type 3-Mediated Calcium Handling in the Vasculature From Hypertensive Rats. J Am Heart Assoc. 2017 Jul 15;6(7). pii: e005812. doi: 10.1161/JAHA.117.005812. PubMed PMID: 28711865; PubMed Central PMCID: PMC5586301. 9: Wu YF, Zhao P, Luo X, Xu JC, Xue L, Zhou Q, Xiong M, Shen J, Peng YB, Yu MF, Chen W, Ma L, Liu QH. Chloroquine inhibits Ca(2+) permeable ion channels-mediated Ca(2+) signaling in primary B lymphocytes. Cell Biosci. 2017 May 23;7:28. doi: 10.1186/s13578-017-0155-5. eCollection 2017. PubMed PMID: 28546857; PubMed Central PMCID: PMC5442594. 10: Cheng Q, Song SH, Augustine GJ. Calcium-Dependent and Synapsin-Dependent Pathways for the Presynaptic Actions of BDNF. Front Cell Neurosci. 2017 Mar 24;11:75. doi: 10.3389/fncel.2017.00075. eCollection 2017. PubMed PMID: 28392759; PubMed Central PMCID: PMC5364187. 11: Abdoul-Azize S, Dubus I, Vannier JP. [Modulation of glucocorticoid sensitivity in acute lymphoblastic leukemia: Pyr3, a new therapeutic tool?]. Med Sci (Paris). 2017 Feb;33(2):130-132. doi: 10.1051/medsci/20173302005. Epub 2017 Feb 27. French. PubMed PMID: 28240201. 12: Sharma A, Nakade UP, Choudhury S, Garg SK. Functional involvement of protein kinase C, Rho-kinase and TRPC3 decreases while PLC increases with advancement of pregnancy in mediating oxytocin-induced myometrial contractions in water buffaloes (Bubalus bubalis). Theriogenology. 2017 Apr 1;92:176-189. doi: 10.1016/j.theriogenology.2016.12.008. Epub 2016 Dec 7. PubMed PMID: 28237334. 13: Wang L, Li J, Zhang J, He Q, Weng X, Huang Y, Guan M, Qiu C. Inhibition of TRPC3 downregulates airway hyperresponsiveness, remodeling of OVA-sensitized mouse. Biochem Biophys Res Commun. 2017 Feb 26;484(1):209-217. doi: 10.1016/j.bbrc.2016.12.138. Epub 2016 Dec 26. PubMed PMID: 28034747. 14: 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. 15: Phelan KD, Shwe UT, Cozart MA, Wu H, Mock MM, Abramowitz J, Birnbaumer L, Zheng F. TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice. Epilepsia. 2017 Feb;58(2):247-254. doi: 10.1111/epi.13648. Epub 2016 Dec 24. PubMed PMID: 28012173; PubMed Central PMCID: PMC5291823. 16: Álvarez-Miguel I, Cidad P, Pérez-García MT, López-López JR. Differences in TRPC3 and TRPC6 channels assembly in mesenteric vascular smooth muscle cells in essential hypertension. J Physiol. 2017 Mar 1;595(5):1497-1513. doi: 10.1113/JP273327. Epub 2016 Dec 29. PubMed PMID: 27861908; PubMed Central PMCID: PMC5330869. 17: 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. 18: Flores-Soto E, Reyes-García J, Carbajal-García A, Campuzano-González E, Perusquía M, Sommer B, Montaño LM. Sex steroids effects on guinea pig airway smooth muscle tone and intracellular Ca(2+) basal levels. Mol Cell Endocrinol. 2017 Jan 5;439:444-456. doi: 10.1016/j.mce.2016.10.004. Epub 2016 Oct 4. PubMed PMID: 27717744. 19: Oda K, Umemura M, Nakakaji R, Tanaka R, Sato I, Nagasako A, Oyamada C, Baljinnyam E, Katsumata M, Xie LH, Narikawa M, Yamaguchi Y, Akimoto T, Ohtake M, Fujita T, Yokoyama U, Iwatsubo K, Aihara M, Ishikawa Y. Transient receptor potential cation 3 channel regulates melanoma proliferation and migration. J Physiol Sci. 2017 Jul;67(4):497-505. doi: 10.1007/s12576-016-0480-1. Epub 2016 Sep 9. PubMed PMID: 27613608. 20: Wang Y, Wang Y, Li GR. TRPC1/TRPC3 channels mediate lysophosphatidylcholine-induced apoptosis in cultured human coronary artery smooth muscles cells. Oncotarget. 2016 Aug 9;7(32):50937-50951. doi: 10.18632/oncotarget.10853. PubMed PMID: 27472391; PubMed Central PMCID: PMC5239449.