GSK2193874 | CAS#1336960-13-4 | TRPV4 channel Antagonist

MedKoo Cat#: 531870 | Name: GSK2193874

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Description:

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

GSK2193874 is a potent antagonist of TRPV4 channels, blocking the influx of calcium induced by the TRPV4 agonist GSK634775 with IC50 values of 2, 5, and 40 nM. It is selective for TRPV4 over ~200 other human receptors, channels, and enzymes.

Chemical Structure

GSK2193874

CAS#1336960-13-4

Theoretical Analysis

MedKoo Cat#: 531870

Name: GSK2193874

CAS#: 1336960-13-4

Chemical Formula: C37H38BrF3N4O

Exact Mass: 690.2181

Molecular Weight: 691.64

Elemental Analysis: C, 64.25; H, 5.54; Br, 11.55; F, 8.24; N, 8.10; O, 2.31

Price and Availability

Size	Price	Availability	Quantity
10mg	USD 450.00	2 Weeks
25mg	USD 850.00	2 Weeks

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Synonym

GSK2193874; GSK 2193874; GSK-2193874; GSK2193874A; GSK 2193874A; GSK-2193874A

IUPAC/Chemical Name

7-bromo-N-(1-phenylcyclopropyl)-3-[(4-piperidin-1-ylpiperidin-1-yl) methyl]-2-[3-(trifluoromethyl)phenyl]quinoline-4-carboxamide

InChi Key

UIVOZBSCHXCGPS-UHFFFAOYSA-N

InChi Code

InChI=1S/C37H38BrF3N4O/c38-28-12-13-30-32(23-28)42-34(25-8-7-11-27(22-25)37(39,40)41)31(24-44-20-14-29(15-21-44)45-18-5-2-6-19-45)33(30)35(46)43-36(16-17-36)26-9-3-1-4-10-26/h1,3-4,7-13,22-23,29H,2,5-6,14-21,24H2,(H,43,46)

SMILES Code

O=C(C1=C(CN2CCC(N3CCCCC3)CC2)C(C4=CC=CC(C(F)(F)F)=C4)=NC5=CC(Br)=CC=C15)NC6(C7=CC=CC=C7)CC6

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

>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

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

GSK2193874 is an orally active, potent, and selective TRPV4 antagonist with IC50s of 2 nM and 40 nM for rTRPV4 and hTRPV4.

In vitro activity:

GSK2193874 was identified as a selective, orally active TRPV4 blocker that inhibits Ca(2+) influx through recombinant TRPV4 channels and native endothelial TRPV4 currents. Reference: Sci Transl Med. 2012 Nov 7;4(159):159ra148. https://pubmed.ncbi.nlm.nih.gov/23136043/

In vivo activity:

GSK2193874 treatment markedly reduced the amount of atrial fibrosis (P < 0.001 versus vehicle). Immunostaining showed that the expression of α-SMA in the atria increased in the vehicle-treated rats (P < 0.001 versus sham, Figure 5B). GSK2193874 reduced the expression of α-SMA (P < 0.001 versus vehicle). Expressions of collagen-1, collagen-3, α-SMA, IL-6, TNF-α, and TGF-β1 were significantly upregulated in the atria of vehicle-treated rats compared with sham rats. Again, GSK2193874 treatment attenuated all the effects above (Figure 5, C and D). Reference: Biol Lett. 2022 Jun;18(6):20220129. https://pubmed.ncbi.nlm.nih.gov/35702981/

	Solvent	mg/mL	mM
Solubility
	DMF	15.0	21.69
	DMSO	62.2	89.85
	Ethanol	32.5	46.99
	Ethanol:PBS (pH 7.2) (1:2)	0.3	0.43

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 691.64 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. Thorneloe KS, Cheung M, Bao W, Alsaid H, Lenhard S, Jian MY, Costell M, Maniscalco-Hauk K, Krawiec JA, Olzinski A, Gordon E, Lozinskaya I, Elefante L, Qin P, Matasic DS, James C, Tunstead J, Donovan B, Kallal L, Waszkiewicz A, Vaidya K, Davenport EA, Larkin J, Burgert M, Casillas LN, Marquis RW, Ye G, Eidam HS, Goodman KB, Toomey JR, Roethke TJ, Jucker BM, Schnackenberg CG, Townsley MI, Lepore JJ, Willette RN. An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure. Sci Transl Med. 2012 Nov 7;4(159):159ra148. doi: 10.1126/scitranslmed.3004276. PMID: 23136043. 2. O'Brien F, Staunton CA, Barrett-Jolley R. Systemic application of the transient receptor potential vanilloid-type 4 antagonist GSK2193874 induces tail vasodilation in a mouse model of thermoregulation. Biol Lett. 2022 Jun;18(6):20220129. doi: 10.1098/rsbl.2022.0129. Epub 2022 Jun 15. PMID: 35702981; PMCID: PMC9198786. 3. Liao J, Wu Q, Qian C, Zhao N, Zhao Z, Lu K, Zhang S, Dong Q, Chen L, Li Q, Du Y. TRPV4 blockade suppresses atrial fibrillation in sterile pericarditis rats. JCI Insight. 2020 Dec 3;5(23):e137528. doi: 10.1172/jci.insight.137528. PMID: 33119551; PMCID: PMC7714415.

In vitro protocol:

In vivo protocol:

1. O'Brien F, Staunton CA, Barrett-Jolley R. Systemic application of the transient receptor potential vanilloid-type 4 antagonist GSK2193874 induces tail vasodilation in a mouse model of thermoregulation. Biol Lett. 2022 Jun;18(6):20220129. doi: 10.1098/rsbl.2022.0129. Epub 2022 Jun 15. PMID: 35702981; PMCID: PMC9198786. 2. Liao J, Wu Q, Qian C, Zhao N, Zhao Z, Lu K, Zhang S, Dong Q, Chen L, Li Q, Du Y. TRPV4 blockade suppresses atrial fibrillation in sterile pericarditis rats. JCI Insight. 2020 Dec 3;5(23):e137528. doi: 10.1172/jci.insight.137528. PMID: 33119551; PMCID: PMC7714415.

1: Buday T, Kovacikova L, Ruzinak R, Plevkova J. TRPV4 antagonist GSK2193874 does not modulate cough response to osmotic stimuli. Respir Physiol Neurobiol. 2017 Feb;236:1-4. doi: 10.1016/j.resp.2016.10.010. PubMed PMID: 27989888. 2: Gu QD, Moss CR 2nd, Kettelhut KL, Gilbert CA, Hu H. Activation of TRPV4 Regulates Respiration through Indirect Activation of Bronchopulmonary Sensory Neurons. Front Physiol. 2016 Feb 29;7:65. doi: 10.3389/fphys.2016.00065. PubMed PMID: 26973533; PubMed Central PMCID: PMC4770051. 3: Yin J, Michalick L, Tang C, Tabuchi A, Goldenberg N, Dan Q, Awwad K, Wang L, Erfinanda L, Nouailles G, Witzenrath M, Vogelzang A, Lv L, Lee WL, Zhang H, Rotstein O, Kapus A, Szaszi K, Fleming I, Liedtke WB, Kuppe H, Kuebler WM. Role of Transient Receptor Potential Vanilloid 4 in Neutrophil Activation and Acute Lung Injury. Am J Respir Cell Mol Biol. 2016 Mar;54(3):370-83. doi: 10.1165/rcmb.2014-0225OC. PubMed PMID: 26222277. 4: Pankey EA, Zsombok A, Lasker GF, Kadowitz PJ. Analysis of responses to the TRPV4 agonist GSK1016790A in the pulmonary vascular bed of the intact-chest rat. Am J Physiol Heart Circ Physiol. 2014 Jan 1;306(1):H33-40. doi: 10.1152/ajpheart.00303.2013. PubMed PMID: 24186096; PubMed Central PMCID: PMC3920159. 5: Thorneloe KS, Cheung M, Bao W, Alsaid H, Lenhard S, Jian MY, Costell M, Maniscalco-Hauk K, Krawiec JA, Olzinski A, Gordon E, Lozinskaya I, Elefante L, Qin P, Matasic DS, James C, Tunstead J, Donovan B, Kallal L, Waszkiewicz A, Vaidya K, Davenport EA, Larkin J, Burgert M, Casillas LN, Marquis RW, Ye G, Eidam HS, Goodman KB, Toomey JR, Roethke TJ, Jucker BM, Schnackenberg CG, Townsley MI, Lepore JJ, Willette RN. An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure. Sci Transl Med. 2012 Nov 7;4(159):159ra148. doi: 10.1126/scitranslmed.3004276. PubMed PMID: 23136043. 6: Huh D, Leslie DC, Matthews BD, Fraser JP, Jurek S, Hamilton GA, Thorneloe KS, McAlexander MA, Ingber DE. A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a-chip microdevice. Sci Transl Med. 2012 Nov 7;4(159):159ra147. doi: 10.1126/scitranslmed.3004249. PubMed PMID: 23136042.