GW311616A | CAS# 197890-44-1 | HNE Inhibitor

GW-311616A
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 525250

CAS#: 197890-44-1 (HCl)

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

Chemical Structure

GW-311616A

CAS# 197890-44-1 (HCl)

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 525250
Name: GW-311616A
CAS#: 197890-44-1 (HCl)
Chemical Formula: C19H31N3O4S
Exact Mass: 433.18
Molecular Weight: 433.992
Elemental Analysis: C, 57.40; H, 7.86; N, 10.57; O, 16.10; S, 8.07

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 485
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Related CAS #: 198062-54-3 (Free) 197890-44-1 (HCl)

Synonym: GW-311616A; GW 311616A; GW311616A; (+)-GW-311616A

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: NDNKNUMSTIMSHQ-URZKGLGPSA-N

InChi Code: InChI=1S/C19H31N3O4S/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/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

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/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. 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

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.

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.

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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.

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