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MedKoo Cat#: 525250 | Name: GW-311616A
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Description:

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

GW311616A is a potent, intracellular, orally bioavailable, long duration inhibitor of human neutrophil elastase(HNE).

Chemical Structure

GW-311616A
GW-311616A
CAS#197890-44-1 (HCl)

Theoretical Analysis

MedKoo Cat#: 525250

Name: GW-311616A

CAS#: 197890-44-1 (HCl)

Chemical Formula: C19H32ClN3O4S

Exact Mass: 0.0000

Molecular Weight: 433.99

Elemental Analysis: C, 52.58; H, 7.43; Cl, 8.17; N, 9.68; O, 14.75; S, 7.39

Price and Availability

Size Price Availability Quantity
5mg USD 485.00 2 Weeks
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Related CAS #
198062-54-3 (free) 197890-44-1 (HCl)
Synonym
GW-311616A; GW 311616A; GW311616A; (+)-GW-311616A; GW311616 hydrochloride; GW311616 HCl;
IUPAC/Chemical Name
(3S,3aS,6aR)-hexahydro-3-(1-methylethyl)-1-(methylsulfonyl)-4-[(2E)-1-oxo-4-(1-piperidinyl)-2-buten-1-yl]-pyrrolo[3,2-b]pyrrol-2(1H)-one, monohydrochloride
InChi Key
UFCZUKYPBPXODT-OFTZGUNKSA-N
InChi Code
InChI=1S/C19H31N3O4S.ClH/c1-14(2)17-18-15(22(19(17)24)27(3,25)26)9-13-21(18)16(23)8-7-12-20-10-5-4-6-11-20;/h7-8,14-15,17-18H,4-6,9-13H2,1-3H3;1H/b8-7+;/t15-,17+,18-;/m1./s1
SMILES Code
O=C1[C@@H](C(C)C)[C@@](N(C(/C=C/CN2CCCCC2)=O)CC3)([H])[C@]3([H])N1S(=O)(C)=O.[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
Product Data
Product Data
Instruction
View handling instruction
Biological target:
GW-311616 is a potent, orally bioavailable, long duration and selective human neutrophil elastase (HNE) inhibitor with IC50 value of 22 nM and Ki value of 0.31 nM.
In vitro activity:
GW311616A inhibited NE (20 nM)-induced loss of VE-cadherin at 200 nM and completely reversed NE’s effect at 1 μM. However, GW311616A effectively blocked NE-induced F-actin formation even at the concentration of 100 nM. Reference: Cells. 2022 Jul 25;11(15):2288. https://pubmed.ncbi.nlm.nih.gov/35892585/
In vivo activity:
GW311616A treatment inhibited serum NE activity by 60% within 1 week of treatment, and this inhibitory effect was sustained during the treatment. GW311616A inhibition of NE activity resulted in significant reductions in HFD-induced bodyweight gain (Figure 4I) and fasting blood glucose levels (Figure 4J). Moreover, both insulin sensitivity and glucose tolerance were significantly improved in the obese WT mice treated with GW311616A for 5 to 6 weeks, compared with the vehicle-treated mice (Figures 4K–4M). Interestingly, GW311616A also significantly increased the level of HMW adiponectin and the ratio of HMW adiponectin to total adiponectin in the sera of HFD-induced obese mice (Figures 4N & 4O). Reference: Cell Metab. 2013 Apr 2;17(4):534-48. https://pubmed.ncbi.nlm.nih.gov/23562077/
Solvent mg/mL mM
Solubility
DMF 30.0 69.13
DMSO 65.0 149.77
DMSO:PBS (pH 7.2) (1:4) 0.3 0.58
Ethanol 10.0 23.04
Water 100.0 230.42
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 433.99 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.

Recalculate based on batch purity %
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. Ushakumari CJ, Zhou QL, Wang YH, Na S, Rigor MC, Zhou CY, Kroll MK, Lin BD, Jiang ZY. Neutrophil Elastase Increases Vascular Permeability and Leukocyte Transmigration in Cultured Endothelial Cells and Obese Mice. Cells. 2022 Jul 25;11(15):2288. doi: 10.3390/cells11152288. PMID: 35892585; PMCID: PMC9332277. 2. Jiang KL, Ma PP, Yang XQ, Zhong L, Wang H, Zhu XY, Liu BZ. Neutrophil elastase and its therapeutic effect on leukemia cells. Mol Med Rep. 2015 Sep;12(3):4165-4172. doi: 10.3892/mmr.2015.3946. Epub 2015 Jun 17. PMID: 26081156; PMCID: PMC4526057. 3. Khomtchouk KM, Joseph LI, Khomtchouk BB, Kouhi A, Massa S, Xia A, Koliesnik I, Pletzer D, Bollyky PL, Santa Maria PL. Treatment with a neutrophil elastase inhibitor and ofloxacin reduces P. aeruginosa burden in a mouse model of chronic suppurative otitis media. NPJ Biofilms Microbiomes. 2021 Apr 6;7(1):31. doi: 10.1038/s41522-021-00200-z. PMID: 33824337; PMCID: PMC8024339. 4. Mansuy-Aubert V, Zhou QL, Xie X, Gong Z, Huang JY, Khan AR, Aubert G, Candelaria K, Thomas S, Shin DJ, Booth S, Baig SM, Bilal A, Hwang D, Zhang H, Lovell-Badge R, Smith SR, Awan FR, Jiang ZY. Imbalance between neutrophil elastase and its inhibitor α1-antitrypsin in obesity alters insulin sensitivity, inflammation, and energy expenditure. Cell Metab. 2013 Apr 2;17(4):534-48. doi: 10.1016/j.cmet.2013.03.005. PMID: 23562077; PMCID: PMC3646573.
In vitro protocol:
1. Ushakumari CJ, Zhou QL, Wang YH, Na S, Rigor MC, Zhou CY, Kroll MK, Lin BD, Jiang ZY. Neutrophil Elastase Increases Vascular Permeability and Leukocyte Transmigration in Cultured Endothelial Cells and Obese Mice. Cells. 2022 Jul 25;11(15):2288. doi: 10.3390/cells11152288. PMID: 35892585; PMCID: PMC9332277. 2. Jiang KL, Ma PP, Yang XQ, Zhong L, Wang H, Zhu XY, Liu BZ. Neutrophil elastase and its therapeutic effect on leukemia cells. Mol Med Rep. 2015 Sep;12(3):4165-4172. doi: 10.3892/mmr.2015.3946. Epub 2015 Jun 17. PMID: 26081156; PMCID: PMC4526057.
In vivo protocol:
1. Khomtchouk KM, Joseph LI, Khomtchouk BB, Kouhi A, Massa S, Xia A, Koliesnik I, Pletzer D, Bollyky PL, Santa Maria PL. Treatment with a neutrophil elastase inhibitor and ofloxacin reduces P. aeruginosa burden in a mouse model of chronic suppurative otitis media. NPJ Biofilms Microbiomes. 2021 Apr 6;7(1):31. doi: 10.1038/s41522-021-00200-z. PMID: 33824337; PMCID: PMC8024339. 2. Mansuy-Aubert V, Zhou QL, Xie X, Gong Z, Huang JY, Khan AR, Aubert G, Candelaria K, Thomas S, Shin DJ, Booth S, Baig SM, Bilal A, Hwang D, Zhang H, Lovell-Badge R, Smith SR, Awan FR, Jiang ZY. Imbalance between neutrophil elastase and its inhibitor α1-antitrypsin in obesity alters insulin sensitivity, inflammation, and energy expenditure. Cell Metab. 2013 Apr 2;17(4):534-48. doi: 10.1016/j.cmet.2013.03.005. PMID: 23562077; PMCID: PMC3646573.
1: Jiang KL, Ma PP, Yang XQ, Zhong L, Wang H, Zhu XY, Liu BZ. Neutrophil elastase and its therapeutic effect on leukemia cells. Mol Med Rep. 2015 Sep;12(3):4165-72. doi: 10.3892/mmr.2015.3946. Epub 2015 Jun 17. PubMed PMID: 26081156; PubMed Central PMCID: PMC4526057. 2: Ma PP, Zhu D, Liu BZ, Zhong L, Zhu XY, Wang H, Zhang X, Gao YM, Hu XX. [Neutrophil elastase inhibitor on proliferation and apoptosis of U937 cells]. Zhonghua Xue Ye Xue Za Zhi. 2013 Jun;34(6):507-11. doi: 10.3760/cma.j.issn.0253-2727.2013.06.011. Chinese. PubMed PMID: 23827109. 3: Mansuy-Aubert V, Zhou QL, Xie X, Gong Z, Huang JY, Khan AR, Aubert G, Candelaria K, Thomas S, Shin DJ, Booth S, Baig SM, Bilal A, Hwang D, Zhang H, Lovell-Badge R, Smith SR, Awan FR, Jiang ZY. Imbalance between neutrophil elastase and its inhibitor α1-antitrypsin in obesity alters insulin sensitivity, inflammation, and energy expenditure. Cell Metab. 2013 Apr 2;17(4):534-48. doi: 10.1016/j.cmet.2013.03.005. PubMed PMID: 23562077; PubMed Central PMCID: PMC3646573. 4: Benedek B, Kopp B, Melzig MF. Achillea millefolium L. s.l. -- is the anti-inflammatory activity mediated by protease inhibition? J Ethnopharmacol. 2007 Sep 5;113(2):312-7. Epub 2007 Jul 3. PubMed PMID: 17689902. 5: Ohbayashi H. Neutrophil elastase inhibitors as treatment for COPD. Expert Opin Investig Drugs. 2002 Jul;11(7):965-80. Review. PubMed PMID: 12084007. 6: Cooke JW, Berry MB, Caine DM, Cardwell KS, Cook JS, Hodgson A. A novel and selective approach to enantiomerically pure bicyclic-trans-lactams via a titanium enolate of a thiopyridyl ester. J Org Chem. 2001 Jan 12;66(1):334-6. PubMed PMID: 11429923. 7: Macdonald SJ, Dowle MD, Harrison LA, Shah P, Johnson MR, Inglis GG, Clarke GD, Smith RA, Humphreys D, Molloy CR, Amour A, Dixon M, Murkitt G, Godward RE, Padfield T, Skarzynski T, Singh OM, Kumar KA, Fleetwood G, Hodgson ST, Hardy GW, Finch H. The discovery of a potent, intracellular, orally bioavailable, long duration inhibitor of human neutrophil elastase--GW311616A a development candidate. Bioorg Med Chem Lett. 2001 Apr 9;11(7):895-8. PubMed PMID: 11294386. 8: Dear GJ, Ayrton J, Plumb R, Fraser IJ. The rapid identification of drug metabolites using capillary liquid chromatography coupled to an ion trap mass spectrometer. Rapid Commun Mass Spectrom. 1999;13(5):456-63. PubMed PMID: 10209877.