WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H530605
CAS#: 214358-33-5 (HCl)
Description: 1400W is a highly selective inducible nitric oxide synthase inhibitor and is a potential disease modifier in the rat kainate model of temporal lobe epilepsy. 1400W reduces ischemia reperfusion injury in an ex-vivo porcine model of the donation after circulatory death kidney donor. 1400W ameliorates acute hypobaric hypoxia/reoxygenation-induced cognitive deficits by suppressing the induction of inducible nitric oxide synthase in rat cerebral cortex microglia. 1400W blocks death pathway of LPS-induced activated-microglia to preOLs.
Hodoodo Cat#: H530605
Name: 1400W HCl
CAS#: 214358-33-5 (HCl)
Chemical Formula: C10H17Cl2N3
Exact Mass: 249.08
Molecular Weight: 250.167
Elemental Analysis: C, 48.01; H, 6.85; Cl, 28.34; N, 16.80
Related CAS #: 180001-34-7 (free base) 214358-33-5 (HCl)
Synonym: 1400W HCl; 1400W hydrochloride; 1400W (hydrochloride).
IUPAC/Chemical Name: N-[[3-(aminomethyl)phenyl]methyl]-ethanimidamide, dihydrochloride
InChi Key: WDJHSQZCZGPGAA-UHFFFAOYSA-N
InChi Code: InChI=1S/C10H15N3.2ClH/c1-8(12)13-7-10-4-2-3-9(5-10)6-11;;/h2-5H,6-7,11H2,1H3,(H2,12,13);2*1H
SMILES Code: CC(NCC1=CC=CC(CN)=C1)=N.[H]Cl.[H]Cl
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:
| Biological target: | 1400W dihydrochloride is an inhibitor of human inducible NO synthase with Ki values of 7 nM. |
| In vitro activity: | First, the growth of NS previously generated after a seven-day culture of adherent U87MG cells in GSC-M, as described in the Methods’ section, was examined following treatment with 1400W (100 μM) for 48 h. In these conditions, NOS2 inhibitor significantly affected the GSC growth, as assayed by measuring the sphere average area in mm2. Indeed, as shown in Figure 2A, while the average surface of untreated NS after 48 h culture was increasing by >10%, the addition of 1400W led to a ~22–23% decrease of NS mean area vs relative T0. Reference: Int J Mol Sci. 2019 Jun; 20(12): 3010. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627770/ |
| In vivo activity: | At 24h post-exposure in rats, 1400W treatment (20 mg/kg, two doses at 12h interval, the first dose was administered 2h post-diazepam) suppressed DFP-induced iNOS and 3-NT upregulation in both hippocampus and piriform cortex as revealed by WB (Fig. 4A–4D) suggesting the pharmacological inhibition of iNOS as well as the suppression of iNOS synthesis. DFP-induced serum nitrite levels were also significantly suppressed by 1400W at 24h post-exposure (Fig. 4E) suggesting the activation of iNOS in peripheral leukocytes by DFP and suppression by 1400W. Reference: Neurobiol Dis. 2020 Jan; 133: 104443. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768773/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 27.5 | 109.93 | |
| Ethanol | 35.0 | 139.91 | |
| Water | 30.0 | 119.96 |
The following data is based on the product molecular weight 250.17 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. Palumbo P, Lombardi F, Augello FR, Giusti I, Luzzi S, Dolo V, Cifone MG, Cinque B. NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line. Int J Mol Sci. 2019 Jun 20;20(12):3010. doi: 10.3390/ijms20123010. PMID: 31226744; PMCID: PMC6627770. 2. Sumayao R Jr, Newsholme P, McMorrow T. Inducible nitric oxide synthase inhibitor 1400W increases Na+ ,K+ -ATPase levels and activity and ameliorates mitochondrial dysfunction in Ctns null kidney proximal tubular epithelial cells. Clin Exp Pharmacol Physiol. 2018 Nov;45(11):1149-1160. doi: 10.1111/1440-1681.12998. Epub 2018 Jul 30. PMID: 29924417. 3. Putra M, Sharma S, Gage M, Gasser G, Hinojo-Perez A, Olson A, Gregory-Flores A, Puttachary S, Wang C, Anantharam V, Thippeswamy T. Inducible nitric oxide synthase inhibitor, 1400W, mitigates DFP-induced long-term neurotoxicity in the rat model. Neurobiol Dis. 2020 Jan;133:104443. doi: 10.1016/j.nbd.2019.03.031. Epub 2019 Mar 30. PMID: 30940499; PMCID: PMC6768773. 4. Staunton CA, Barrett-Jolley R, Djouhri L, Thippeswamy T. Inducible nitric oxide synthase inhibition by 1400W limits pain hypersensitivity in a neuropathic pain rat model. Exp Physiol. 2018 Apr 1;103(4):535-544. doi: 10.1113/EP086764. Epub 2018 Mar 7. PMID: 29441689. |
| In vitro protocol: | 1. Palumbo P, Lombardi F, Augello FR, Giusti I, Luzzi S, Dolo V, Cifone MG, Cinque B. NOS2 inhibitor 1400W Induces Autophagic Flux and Influences Extracellular Vesicle Profile in Human Glioblastoma U87MG Cell Line. Int J Mol Sci. 2019 Jun 20;20(12):3010. doi: 10.3390/ijms20123010. PMID: 31226744; PMCID: PMC6627770. 2. Sumayao R Jr, Newsholme P, McMorrow T. Inducible nitric oxide synthase inhibitor 1400W increases Na+ ,K+ -ATPase levels and activity and ameliorates mitochondrial dysfunction in Ctns null kidney proximal tubular epithelial cells. Clin Exp Pharmacol Physiol. 2018 Nov;45(11):1149-1160. doi: 10.1111/1440-1681.12998. Epub 2018 Jul 30. PMID: 29924417. |
| In vivo protocol: | 1. Putra M, Sharma S, Gage M, Gasser G, Hinojo-Perez A, Olson A, Gregory-Flores A, Puttachary S, Wang C, Anantharam V, Thippeswamy T. Inducible nitric oxide synthase inhibitor, 1400W, mitigates DFP-induced long-term neurotoxicity in the rat model. Neurobiol Dis. 2020 Jan;133:104443. doi: 10.1016/j.nbd.2019.03.031. Epub 2019 Mar 30. PMID: 30940499; PMCID: PMC6768773. 2. Staunton CA, Barrett-Jolley R, Djouhri L, Thippeswamy T. Inducible nitric oxide synthase inhibition by 1400W limits pain hypersensitivity in a neuropathic pain rat model. Exp Physiol. 2018 Apr 1;103(4):535-544. doi: 10.1113/EP086764. Epub 2018 Mar 7. PMID: 29441689. |
1: Puttachary S, Sharma S, Verma S, Yang Y, Putra M, Thippeswamy A, Luo D, Thippeswamy T. 1400W, a highly selective inducible nitric oxide synthase inhibitor is a potential disease modifier in the rat kainate model of temporal lobe epilepsy. Neurobiol Dis. 2016 Sep;93:184-200. doi: 10.1016/j.nbd.2016.05.013. Epub 2016 May 18. PubMed PMID: 27208748.
2: Hosgood SA, Yates PJ, Nicholson ML. 1400W reduces ischemia reperfusion injury in an ex-vivo porcine model of the donation after circulatory death kidney donor. World J Transplant. 2014 Dec 24;4(4):299-305. doi: 10.5500/wjt.v4.i4.299. PubMed PMID: 25540738; PubMed Central PMCID: PMC4274599.
3: Shi Q, Liu X, Wang N, Zheng X, Ran J, Liu Z, Fu J, Zheng J. 1400W ameliorates acute hypobaric hypoxia/reoxygenation-induced cognitive deficits by suppressing the induction of inducible nitric oxide synthase in rat cerebral cortex microglia. Behav Brain Res. 2017 Feb 15;319:188-199. doi: 10.1016/j.bbr.2016.11.039. Epub 2016 Nov 22. PubMed PMID: 27888018.
4: He YF, Chen HJ, Qian LH, Chen GY. [1400W blocks death pathway of LPS-induced activated-microglia to preOLs]. Zhongguo Dang Dai Er Ke Za Zhi. 2010 May;12(5):357-62. Chinese. PubMed PMID: 20497644.
5: Al-Akl NS, Ismail M, Khaliefeh F, Usta J, Abdelnoor AM. Effects of catalase and 1400W on the number of interleukin-4 and interferon-γ secreting spleen cells in mice injected with ovalbumin and alum. Immunopharmacol Immunotoxicol. 2012 Dec;34(6):951-5. doi: 10.3109/08923973.2012.674530. Epub 2012 May 3. PubMed PMID: 22551050.
6: Ersoz N, Guven A, Cayci T, Uysal B, Turk E, Oztas E, Akgul EO, Korkmaz A, Cetiner S. Comparison of the efficacy of melatonin and 1400W on renal ischemia/reperfusion injury: a role for inhibiting iNOS. Ren Fail. 2009;31(8):704-10. doi: 10.3109/08860220903085989. PubMed PMID: 19814638.
7: He YF, Chen HJ, Qian LH, Chen GY. Effect of 1400W on blocking lipopolysaccharide-induced microglial toxicity to preoligodendrocytes. World J Pediatr. 2010 Aug;6(3):249-54. doi: 10.1007/s12519-010-0203-2. Epub 2010 Jun 12. PubMed PMID: 20549418.
8: He YF, Chen HJ, Qian LH, Chen GY. [Effect of 1400W, an inhibitor of inducible nitric oxide synthetase, on blocking the toxicity of lipopolysaccharide-induced activated microglia to preoligodendrocytes]. Zhonghua Er Ke Za Zhi. 2009 Jul;47(7):537-43. Chinese. PubMed PMID: 19951519.
9: Poyrazoglu Y, Yigit T, Harlak A, Mentes O, Gorgulu S, Uzar AI, Kozak O. Effects of prevention of oxidative and nitro-oxidative stress on experimental rat colon anastomosis using acetylcysteine, Ebselen and 1400w. Acta Chir Belg. 2011 Jan-Feb;111(1):26-31. PubMed PMID: 21520784.
10: Rus A, Castro L, Del Moral ML, Peinado A. Inducible NOS inhibitor 1400W reduces hypoxia/re-oxygenation injury in rat lung. Redox Rep. 2010;15(4):169-78. doi: 10.1179/174329210X12650506623609. PubMed PMID: 20663293.
11: Tang Q, Svensson CI, Fitzsimmons B, Webb M, Yaksh TL, Hua XY. Inhibition of spinal constitutive NOS-2 by 1400W attenuates tissue injury and inflammation-induced hyperalgesia and spinal p38 activation. Eur J Neurosci. 2007 May;25(10):2964-72. PubMed PMID: 17561811.
12: Nemec A, Pavlica Z, Petelin M, Crossley DA, Sentjurc M, Jerin A, Erzen D, Zdovc I, Hitti T, Skaleric U. Systemic use of selective iNOS inhibitor 1400W or non-selective NOS inhibitor l-NAME differently affects systemic nitric oxide formation after oral Porphyromonas gingivalis inoculation in mice. Arch Oral Biol. 2010 Jul;55(7):509-14. doi: 10.1016/j.archoralbio.2010.04.003. Epub 2010 Apr 28. PubMed PMID: 20430367.
13: Barker JU, Qi WN, Cai Y, Urbaniak JR, Chen LE. Addition of nitric oxide donor S-nitroso-N-acetylcysteine to selective iNOS inhibitor 1400W further improves contractile function in reperfused skeletal muscle. Microsurgery. 2005;25(4):338-45. PubMed PMID: 15880470.
14: Järvinen K, Vuolteenaho K, Nieminen R, Moilanen T, Knowles RG, Moilanen E. Selective iNOS inhibitor 1400W enhances anti-catabolic IL-10 and reduces destructive MMP-10 in OA cartilage. Survey of the effects of 1400W on inflammatory mediators produced by OA cartilage as detected by protein antibody array. Clin Exp Rheumatol. 2008 Mar-Apr;26(2):275-82. PubMed PMID: 18565249.
15: Ozturk M, Ozler M, Kurt YG, Ozturk B, Uysal B, Ersoz N, Yasar M, Demirbas S, Kurt B, Acikel C, Oztas Y, Arpaci F, Topal T, Ozet A, Ataergin S, Kuzhan O, Oter S, Korkmaz A. Efficacy of melatonin, mercaptoethylguanidine and 1400W in doxorubicin- and trastuzumab-induced cardiotoxicity. J Pineal Res. 2011 Jan;50(1):89-96. doi: 10.1111/j.1600-079X.2010.00818.x. Epub 2010 Nov 9. PubMed PMID: 21062350.
16: Pérez-Asensio FJ, Hurtado O, Burguete MC, Moro MA, Salom JB, Lizasoain I, Torregrosa G, Leza JC, Alborch E, Castillo J, Knowles RG, Lorenzo P. Inhibition of iNOS activity by 1400W decreases glutamate release and ameliorates stroke outcome after experimental ischemia. Neurobiol Dis. 2005 Mar;18(2):375-84. PubMed PMID: 15686966.
17: Patel P, Qi WN, Allen DM, Chen LE, Seaber AV, Stamler JS, Urbaniak JR. Inhibition of iNOS with 1400W improves contractile function and alters nos gene and protein expression in reperfused skeletal muscle. Microsurgery. 2004;24(4):324-31. PubMed PMID: 15274192.
18: Cheng X, Pang CC. Increased vasoconstriction to noradrenaline by 1400W, inhibitor of iNOS, in rats with streptozotocin-induced diabetes. Eur J Pharmacol. 2004 Jan 26;484(2-3):263-8. PubMed PMID: 14744612.
19: Jafarian-Tehrani M, Louin G, Royo NC, Besson VC, Bohme GA, Plotkine M, Marchand-Verrecchia C. 1400W, a potent selective inducible NOS inhibitor, improves histopathological outcome following traumatic brain injury in rats. Nitric Oxide. 2005 Mar;12(2):61-9. Epub 2005 Jan 21. PubMed PMID: 15740979.
20: Chiba Y, Matsuo K, Sakai H, Abe K, Misawa M. Effects of 1400W, a potent selective inducible NOS inhibitor, on histamine- and leukotriene D4-induced relaxation of isolated guinea pig nasal mucosa. Nitric Oxide. 2006 Sep;15(2):142-7. Epub 2006 Jan 25. PubMed PMID: 16442819.
