Synonym
GSK269962 HCl; GSK269962 hydrochloride; GSK269962; GSK 269962; GSK-269962; GSK269962A; GSK 269962A; GSK-269962A; GSK26996B;
IUPAC/Chemical Name
N-[3-[[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-1H-imidazo[4,5-c]pyridin-6-yl]oxy]phenyl]-4-[2-(4-morpholinyl)ethoxy]-benzamide hydrochloride
InChi Key
UYKVMFKKKLLDGL-UHFFFAOYSA-N
InChi Code
InChI=1S/C29H30N8O5.ClH/c1-2-37-24-17-25(31-18-23(24)33-28(37)26-27(30)35-42-34-26)41-22-5-3-4-20(16-22)32-29(38)19-6-8-21(9-7-19)40-15-12-36-10-13-39-14-11-36;/h3-9,16-18H,2,10-15H2,1H3,(H2,30,35)(H,32,38);1H
SMILES Code
O=C(NC1=CC=CC(OC2=CC3=C(N=C(C4=NON=C4N)N3CC)C=N2)=C1)C5=CC=C(OCCN6CCOCC6)C=C5.[H]Cl
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
2934.99.9001
Biological target:
GSK269962A hydrochloride (GSK 269962 hydrochloride) is a potent ROCK inhibitor with IC50s of 1.6 and 4 nM for recombinant human ROCK1 and ROCK2 respectively.
In vitro activity:
In this article, this study characterized two aminofurazan-based inhibitors, GSK269962A [N-(3-{[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-1H-imidazo[4, 5-c]pyridin-6-yl]oxy}phenyl)-4-{[2-(4-morpholinyl)ethyl]-oxy}benzamide] and SB-7720770-B [4-(7-{[(3S)-3-amino-1-pyrrolidinyl]carbonyl}-1-ethyl-1H-imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amine], as members of a novel class of compounds that potently inhibit ROCK enzymatic activity. GSK269962A and SB-772077-B have IC50 values of 1.6 and 5.6 nM toward recombinant human ROCK1, respectively. GSK269962A also exhibited more than 30-fold selectivity against a panel of serine/threonine kinases.
Reference: J Pharmacol Exp Ther. 2007 Jan;320(1):89-98. https://pubmed.ncbi.nlm.nih.gov/17018693/
In vivo activity:
CYP injection resulted in a significant increase in cystometric parameters: basal pressure, threshold pressure, bladder contraction duration, relaxation time, detrusor overactivity index, non-voiding contractions amplitude, and non-voiding contractions frequency as well as increased Evans Blue extravasation into bladder tissue, whereas micturition voiding pressure, voided volume, post-void residual, volume threshold, intercontraction interval, bladder compliance, and volume threshold to elicit non-voiding contractions as well as urothelium thickness were significantly decreased in CYP-injected rats. Administration of GSK 269962 normalized the abovementioned CYP injection-induced changes. Inhibition of ROCK was found to ameliorate CYP-induced detrusor overactivity and bladder inflammation.
Reference: Naunyn Schmiedebergs Arch Pharmacol. 2017 Jun;390(6):613-619. https://pubmed.ncbi.nlm.nih.gov/28220212/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
100.0 |
164.73 |
| Ethanol |
28.0 |
46.12 |
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
607.07
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. Doe C, Bentley R, Behm DJ, Lafferty R, Stavenger R, Jung D, Bamford M, Panchal T, Grygielko E, Wright LL, Smith GK, Chen Z, Webb C, Khandekar S, Yi T, Kirkpatrick R, Dul E, Jolivette L, Marino JP Jr, Willette R, Lee D, Hu E. Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther. 2007 Jan;320(1):89-98. doi: 10.1124/jpet.106.110635. Epub 2006 Oct 3. PMID: 17018693.
2. Wróbel A, Doboszewska U, Rechberger E, Rojek K, Serefko A, Poleszak E, Skalicka-Woźniak K, Dudka J, Wlaź P. Rho kinase inhibition ameliorates cyclophosphamide-induced cystitis in rats. Naunyn Schmiedebergs Arch Pharmacol. 2017 Jun;390(6):613-619. doi: 10.1007/s00210-017-1361-8. Epub 2017 Feb 21. PMID: 28220212; PMCID: PMC5411406.
In vitro protocol:
1. Doe C, Bentley R, Behm DJ, Lafferty R, Stavenger R, Jung D, Bamford M, Panchal T, Grygielko E, Wright LL, Smith GK, Chen Z, Webb C, Khandekar S, Yi T, Kirkpatrick R, Dul E, Jolivette L, Marino JP Jr, Willette R, Lee D, Hu E. Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther. 2007 Jan;320(1):89-98. doi: 10.1124/jpet.106.110635. Epub 2006 Oct 3. PMID: 17018693.
In vivo protocol:
1. Wróbel A, Doboszewska U, Rechberger E, Rojek K, Serefko A, Poleszak E, Skalicka-Woźniak K, Dudka J, Wlaź P. Rho kinase inhibition ameliorates cyclophosphamide-induced cystitis in rats. Naunyn Schmiedebergs Arch Pharmacol. 2017 Jun;390(6):613-619. doi: 10.1007/s00210-017-1361-8. Epub 2017 Feb 21. PMID: 28220212; PMCID: PMC5411406.
1: Wróbel A, Serefko A, Rechberger E, Banczerowska-Górska M, Poleszak E, Dudka J, Skorupska K, Miotła P, Semczuk A, Kulik-Rechberger B, Mandziuk S, Rechberger T. Inhibition of Rho kinase by GSK 269962 reverses both corticosterone-induced detrusor overactivity and depression-like behaviour in rats. Eur J Pharmacol. 2018 Oct 15;837:127-136. doi: 10.1016/j.ejphar.2018.08.027. Epub 2018 Aug 30. PubMed PMID: 30172788.
2: Wróbel A, Doboszewska U, Rechberger E, Rojek K, Serefko A, Poleszak E, Skalicka-Woźniak K, Dudka J, Wlaź P. Rho kinase inhibition ameliorates cyclophosphamide-induced cystitis in rats. Naunyn Schmiedebergs Arch Pharmacol. 2017 Jun;390(6):613-619. doi: 10.1007/s00210-017-1361-8. Epub 2017 Feb 21. PubMed PMID: 28220212; PubMed Central PMCID: PMC5411406.
3: Wróbel A, Rechberger T. The Influence of Maxacalcitol, Vitamin D3 Analog, on Detrusor Overactivity in Conscious Rats. Urology. 2016 Jul;93:224.e7-224.e15. doi: 10.1016/j.urology.2016.03.008. Epub 2016 Mar 23. PubMed PMID: 27018369.
4: Wróbel A, Rechberger T. Ovariectomy May Induce Detrusor Overactivity in Rats: The Therapeutic Role of Rho Kinase Inhibition. Urology. 2016 Jul;93:225.e1-7. doi: 10.1016/j.urology.2016.03.007. Epub 2016 Mar 14. PubMed PMID: 26988893.
5: Wróbel A, Rechberger T. The effect of combined treatment with a β(3) AR agonist and a ROCK inhibitor on detrusor overactivity. Neurourol Urodyn. 2017 Mar;36(3):580-588. doi: 10.1002/nau.22978. Epub 2016 Feb 16. PubMed PMID: 26879338.
6: Wróbel A, Rechberger T. The influence of Rho-kinase inhibition on acetic acid-induced detrusor overactivity. Neurourol Urodyn. 2017 Feb;36(2):263-270. doi: 10.1002/nau.22918. Epub 2015 Nov 6. PubMed PMID: 26546786.
7: Hutchinson JL, Rajagopal SP, Yuan M, Norman JE. Lipopolysaccharide promotes contraction of uterine myocytes via activation of Rho/ROCK signaling pathways. FASEB J. 2014 Jan;28(1):94-105. doi: 10.1096/fj.13-237040. Epub 2013 Sep 27. PubMed PMID: 24076962.
