GSK1016790A | GSK101 | CAS#942206-85-1 |TRPV4 agonist

MedKoo Cat#: 531880 | Name: GSK1016790A

Description:

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

GSK1016790A, also known as GSK101, is a TRPV4 agonist that elicits calcium influx in HEK cells expressing mouse or human TRPV4 (EC50s = 18 and 2.1 nM, respectively).

Chemical Structure

GSK1016790A

CAS#942206-85-1

Theoretical Analysis

MedKoo Cat#: 531880

Name: GSK1016790A

CAS#: 942206-85-1

Chemical Formula: C28H32Cl2N4O6S2

Exact Mass: 654.1140

Molecular Weight: 655.61

Elemental Analysis: C, 51.30; H, 4.92; Cl, 10.81; N, 8.55; O, 14.64; S, 9.78

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 300.00	Ready to ship
50mg	USD 550.00	Ready to ship
100mg	USD 950.00	Ready to ship
250mg	USD 2,150.00	Ready to ship
500mg	USD 3,450.00	Ready to ship

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Synonym

GSK1016790A; GSK-1016790A; GSK 1016790A; GSK101; GSK-101; GSK 101;

IUPAC/Chemical Name

N-[(2S)-1-[4-[(2S)-2-[(2,4-dichlorophenyl)sulfonylamino]-3-hydroxypropanoyl]piperazin-1-yl]-4-methyl-1-oxopentan-2-yl]-1-benzothiophene-2-carboxamide

InChi Key

IVYQPSHHYIAUFO-VXKWHMMOSA-N

InChi Code

InChI=1S/C28H32Cl2N4O6S2/c1-17(2)13-21(31-26(36)24-14-18-5-3-4-6-23(18)41-24)27(37)33-9-11-34(12-10-33)28(38)22(16-35)32-42(39,40)25-8-7-19(29)15-20(25)30/h3-8,14-15,17,21-22,32,35H,9-13,16H2,1-2H3,(H,31,36)/t21-,22-/m0/s1

SMILES Code

O=C(C1=CC2=CC=CC=C2S1)N[C@@H](CC(C)C)C(N3CCN(C([C@@H](NS(=O)(C4=CC=C(Cl)C=C4Cl)=O)CO)=O)CC3)=O

Appearance

Solid powder

Purity

>95% (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

Certificate of Analysis

View CoA: current batch, Lot#A20T08K20

QC Data

View QC data: current batch, Lot#A20T08K20

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

GSK1016790A is a potent and selective transient receptor potential vanilloid 4 (TRPV4) channel agonist.

In vitro activity:

GSK1016790A (GSK101) is a recently discovered specific small molecule agonist of TRPV4. Its effects on physical determinants of TRPV4 activity were evaluated in HeLa cells transiently transfected with TRPV4 (HeLa-TRPV4). GSK101 (10 nM) causes a TRPV4 specific Ca(2+) influx in HeLa-TRPV4 cells, but not in control transfected cells, which can be inhibited by ruthenium red and Ca(2+)-free medium more significantly at the early stage of the activation rather than the late stage, reflecting apparent partial desensitization. Western blot analysis showed that GSK101 activation did not induce an increase in TRPV4 expression at the plasma membrane, but caused an immediate and sustained downregulation of TRPV4 on the plasma membrane in HeLa-TRPV4 cells. Patch clamp analysis also revealed an early partial desensitization of the channel which was Ca(2+)-independent. FRET analysis of TRPV4 subunit assembly demonstrated that the GSK101-induced TRPV4 channel activation/desensitization was not due to alterations in homotetrameric channel formation on the plasma membrane. It is concluded that GSK101 specifically activates TRPV4 channels, leading to a rapid partial desensitization and downregulation of the channel expression on the plasma membrane. Reference: PLoS One. 2011 Feb 14;6(2):e16713. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21339821/

In vivo activity:

Intravenous injection of GSK1016790A at doses of 2-10 μg/kg produced dose-dependent decreases in systemic arterial pressure, small decreases in pulmonary arterial pressure, and small increases in cardiac output, and responses were not altered by the cyclooxygenase inhibitor meclofenamate or the cytochrome P-450 inhibitor miconazole. Injection of GSK1016790A at a dose of 12 μg/kg iv produced cardiovascular collapse that was reversible in some animals. GSK1016790A produced dose-related decreases in pulmonary and systemic arterial pressure when baseline tone in the pulmonary vascular bed was increased with U-46619. After treatment with the nitric oxide synthase (NOS) inhibitor N-nitro-l-arginine methyl ester, GSK1016790A produced larger decreases in systemic arterial pressure and dose-dependent increases in pulmonary arterial pressure followed by a small decrease. These results demonstrate that GSK1016790A has vasodilator activity in pulmonary and systemic vascular beds and that when NOS is inhibited, GSK1016790A produced pulmonary vasoconstrictor responses that were attenuated by the L-type Ca(2+) channel antagonist isradipine. Reference: Am J Physiol Heart Circ Physiol. 2014 Jan 1;306(1):H33-40. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24186096/

	Solvent	mg/mL	mM
Solubility
	DMSO	33.0	50.33

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 655.61 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:

In vitro protocol:

1. Jin M, Wu Z, Chen L, Jaimes J, Collins D, Walters ET, O'Neil RG. Determinants of TRPV4 activity following selective activation by small molecule agonist GSK1016790A. PLoS One. 2011 Feb 14;6(2):e16713. doi: 10.1371/journal.pone.0016713. PMID: 21339821; PMCID: PMC3038856. 2. Thorneloe KS, Sulpizio AC, Lin Z, Figueroa DJ, Clouse AK, McCafferty GP, Chendrimada TP, Lashinger ES, Gordon E, Evans L, Misajet BA, Demarini DJ, Nation JH, Casillas LN, Marquis RW, Votta BJ, Sheardown SA, Xu X, Brooks DP, Laping NJ, Westfall TD. N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I. J Pharmacol Exp Ther. 2008 Aug;326(2):432-42. doi: 10.1124/jpet.108.139295. Epub 2008 May 22. Erratum in: J Pharmacol Exp Ther. 2011 Jul;338(1):410. PMID: 18499743.

In vivo protocol:

1. Thorneloe KS, Sulpizio AC, Lin Z, Figueroa DJ, Clouse AK, McCafferty GP, Chendrimada TP, Lashinger ES, Gordon E, Evans L, Misajet BA, Demarini DJ, Nation JH, Casillas LN, Marquis RW, Votta BJ, Sheardown SA, Xu X, Brooks DP, Laping NJ, Westfall TD. N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I. J Pharmacol Exp Ther. 2008 Aug;326(2):432-42. doi: 10.1124/jpet.108.139295. Epub 2008 May 22. Erratum in: J Pharmacol Exp Ther. 2011 Jul;338(1):410. PMID: 18499743. 2. 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. Epub 2013 Nov 1. PMID: 24186096; PMCID: PMC3920159.

1: Addison MP, Singh TU, Parida S, Choudhury S, Kasa JK, Sukumaran SV, Darzi SA, Kandasamy K, Singh V, Kumar D, Mishra SK. NO synthase inhibition attenuates EDHF-mediated relaxation induced by TRPV4 channel agonist GSK1016790A in the rat pulmonary artery: Role of TxA2. Pharmacol Rep. 2016 Jun;68(3):620-6. doi: 10.1016/j.pharep.2016.01.003. PubMed PMID: 26991376. 2: 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. 3: Sullivan MN, Francis M, Pitts NL, Taylor MS, Earley S. Optical recording reveals novel properties of GSK1016790A-induced vanilloid transient receptor potential channel TRPV4 activity in primary human endothelial cells. Mol Pharmacol. 2012 Sep;82(3):464-72. doi: 10.1124/mol.112.078584. PubMed PMID: 22689561; PubMed Central PMCID: PMC3422704. 4: Jin M, Wu Z, Chen L, Jaimes J, Collins D, Walters ET, O'Neil RG. Determinants of TRPV4 activity following selective activation by small molecule agonist GSK1016790A. PLoS One. 2011 Feb 14;6(2):e16713. doi: 10.1371/journal.pone.0016713. PubMed PMID: 21339821; PubMed Central PMCID: PMC3038856. 5: Thorneloe KS, Sulpizio AC, Lin Z, Figueroa DJ, Clouse AK, McCafferty GP, Chendrimada TP, Lashinger ES, Gordon E, Evans L, Misajet BA, Demarini DJ, Nation JH, Casillas LN, Marquis RW, Votta BJ, Sheardown SA, Xu X, Brooks DP, Laping NJ, Westfall TD. N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1 -piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I. J Pharmacol Exp Ther. 2008 Aug;326(2):432-42. doi: 10.1124/jpet.108.139295. Erratum in: J Pharmacol Exp Ther. 2011 Jul;338(1):410. PubMed PMID: 18499743.