GW280264X | CAS#866924-39-2 | ADAM17 inhibitor

MedKoo Cat#: 555806 | Name: GW280264X

Description:

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

GW280264X is an ADAM17 inhibitor.

Chemical Structure

GW280264X

CAS#866924-39-2

Theoretical Analysis

MedKoo Cat#: 555806

Name: GW280264X

CAS#: 866924-39-2

Chemical Formula: C28H41N5O6S

Exact Mass: 575.2778

Molecular Weight: 575.73

Elemental Analysis: C, 58.41; H, 7.18; N, 12.16; O, 16.67; S, 5.57

Price and Availability

Size	Price	Availability
5mg	USD 350.00	2 Weeks
10mg	USD 650.00	2 Weeks
1g	USD 4,650.00	2 Weeks

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Related CAS #

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Synonym

GW280264X; GW-280264X; GW 280264X; GW280264; GW-280264; GW 280264;

IUPAC/Chemical Name

Benzyl N-[(5S)-5-[[(2R,3S)-3-(Formylhydroxyamino)-2-(2-methylpropyl)-1-oxohexyl]amino]-6-oxo-6-(2-thiazolylamino)hexyl]-carbamate

InChi Key

SKJLITFHSZNZMQ-SGNDLWITSA-N

InChi Code

InChI=1S/C28H41N5O6S/c1-4-10-24(33(38)19-34)22(17-20(2)3)25(35)31-23(26(36)32-27-29-15-16-40-27)13-8-9-14-30-28(37)39-18-21-11-6-5-7-12-21/h5-7,11-12,15-16,19-20,22-24,38H,4,8-10,13-14,17-18H2,1-3H3,(H,30,37)(H,31,35)(H,29,32,36)/t22-,23+,24+/m1/s1

SMILES Code

O=C(OCC1=CC=CC=C1)NCCCC[C@H](NC([C@H](CC(C)C)[C@@H](N(C=O)O)CCC)=O)C(NC2=NC=CS2)=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

>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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A20O12B28

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

GW280264X potently blocks TACE (ADAM17) and ADAM10 with IC50s of 8.0 nM and 11.5 nM, respectively.

In vitro activity:

In further agreement with the differential ability of the 2 compounds to block the PMA-mediated shedding, only the mixed TACE/ADAM10 inhibitor GW280264X substantially restored adhesion to PMA-stimulated cells, whereas the selective ADAM10 inhibitor GI254023X had a minimal effect. Reference: Blood. 2003 Aug 15;102(4):1186-95. https://pubmed.ncbi.nlm.nih.gov/12714508/

In vivo activity:

C57BL/6 mice were subjected to SCI (spinal cord injury) and were treated either with GW280264x (combined ADAM10/ADAM17 inhibition), GI254023x (specific ADAM10 inhibition), or PBS + DMSO (control) (Fig. 1A). Mice treated with GW280264x showed significantly improved functional recovery compared to the control group (Fig. 1B). Reference: Brain Behav Immun. 2019 Aug;80:129-145. https://pubmed.ncbi.nlm.nih.gov/30851378/

	Solvent	mg/mL	mM
Solubility
	DMSO	91.3	158.56

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 575.73 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. Hedemann N, Herz A, Schiepanski JH, Dittrich J, Sebens S, Dempfle A, Feuerborn J, Rogmans C, Tribian N, Flörkemeier I, Weimer J, Krüger S, Maass N, Bauerschlag DO. ADAM17 Inhibition Increases the Impact of Cisplatin Treatment in Ovarian Cancer Spheroids. Cancers (Basel). 2021 Apr 23;13(9):2039. doi: 10.3390/cancers13092039. PMID: 33922533; PMCID: PMC8122950. 2. Hundhausen C, Misztela D, Berkhout TA, Broadway N, Saftig P, Reiss K, Hartmann D, Fahrenholz F, Postina R, Matthews V, Kallen KJ, Rose-John S, Ludwig A. The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion. Blood. 2003 Aug 15;102(4):1186-95. doi: 10.1182/blood-2002-12-3775. Epub 2003 Apr 24. PMID: 12714508. 3. Sommer D, Corstjens I, Sanchez S, Dooley D, Lemmens S, Van Broeckhoven J, Bogie J, Vanmierlo T, Vidal PM, Rose-John S, Gou-Fabregas M, Hendrix S. ADAM17-deficiency on microglia but not on macrophages promotes phagocytosis and functional recovery after spinal cord injury. Brain Behav Immun. 2019 Aug;80:129-145. doi: 10.1016/j.bbi.2019.02.032. Epub 2019 Mar 6. PMID: 30851378.

In vitro protocol:

In vivo protocol:

1. Sommer D, Corstjens I, Sanchez S, Dooley D, Lemmens S, Van Broeckhoven J, Bogie J, Vanmierlo T, Vidal PM, Rose-John S, Gou-Fabregas M, Hendrix S. ADAM17-deficiency on microglia but not on macrophages promotes phagocytosis and functional recovery after spinal cord injury. Brain Behav Immun. 2019 Aug;80:129-145. doi: 10.1016/j.bbi.2019.02.032. Epub 2019 Mar 6. PMID: 30851378.

1: Yang J, LeBlanc ME, Cano I, Saez-Torres KL, Saint-Geniez M, Ng YS, D'Amore PA. ADAM10 and ADAM17 proteases mediate proinflammatory cytokine-induced and constitutive cleavage of endomucin from the endothelial surface. J Biol Chem. 2020 May 8;295(19):6641-6651. doi: 10.1074/jbc.RA119.011192. Epub 2020 Mar 19. PMID: 32193206; PMCID: PMC7212652. 2: Kouam PN, Rezniczek GA, Adamietz IA, Bühler H. Ionizing radiation increases the endothelial permeability and the transendothelial migration of tumor cells through ADAM10-activation and subsequent degradation of VE-cadherin. BMC Cancer. 2019 Oct 16;19(1):958. doi: 10.1186/s12885-019-6219-7. PMID: 31619190; PMCID: PMC6794838. 3: Saad MI, McLeod L, Yu L, Ebi H, Ruwanpura S, Sagi I, Rose-John S, Jenkins BJ. The ADAM17 protease promotes tobacco smoke carcinogen-induced lung tumorigenesis. Carcinogenesis. 2020 Jun 17;41(4):527-538. doi: 10.1093/carcin/bgz123. PMID: 31257400. 4: Malemud CJ. Inhibition of MMPs and ADAM/ADAMTS. Biochem Pharmacol. 2019 Jul;165:33-40. doi: 10.1016/j.bcp.2019.02.033. Epub 2019 Feb 28. PMID: 30826330; PMCID: PMC6557692. 5: Hedemann N, Rogmans C, Sebens S, Wesch D, Reichert M, Schmidt-Arras D, Oberg HH, Pecks U, van Mackelenbergh M, Weimer J, Arnold N, Maass N, Bauerschlag DO. ADAM17 inhibition enhances platinum efficiency in ovarian cancer. Oncotarget. 2018 Mar 23;9(22):16043-16058. doi: 10.18632/oncotarget.24682. PMID: 29662625; PMCID: PMC5882316. 6: Maretzky T, Swendeman S, Mogollon E, Weskamp G, Sahin U, Reiss K, Blobel CP. Characterization of the catalytic properties of the membrane-anchored metalloproteinase ADAM9 in cell-based assays. Biochem J. 2017 Apr 13;474(9):1467-1479. doi: 10.1042/BCJ20170075. PMID: 28264989. 7: Urriola-Muñoz P, Lagos-Cabré R, Moreno RD. A mechanism of male germ cell apoptosis induced by bisphenol-A and nonylphenol involving ADAM17 and p38 MAPK activation. PLoS One. 2014 Dec 4;9(12):e113793. doi: 10.1371/journal.pone.0113793. PMID: 25474107; PMCID: PMC4256297. 8: Wolpert F, Tritschler I, Steinle A, Weller M, Eisele G. A disintegrin and metalloproteinases 10 and 17 modulate the immunogenicity of glioblastoma- initiating cells. Neuro Oncol. 2014 Mar;16(3):382-91. doi: 10.1093/neuonc/not232. Epub 2013 Dec 9. PMID: 24327582; PMCID: PMC3922520. 9: Dreymueller D, Martin C, Kogel T, Pruessmeyer J, Hess FM, Horiuchi K, Uhlig S, Ludwig A. Lung endothelial ADAM17 regulates the acute inflammatory response to lipopolysaccharide. EMBO Mol Med. 2012 May;4(5):412-23. doi: 10.1002/emmm.201200217. Epub 2012 Feb 24. PMID: 22367719; PMCID: PMC3403298. 10: Durairajan SS, Liu LF, Lu JH, Koo I, Maruyama K, Chung SK, Huang JD, Li M. Stimulation of non-amyloidogenic processing of amyloid-β protein precursor by cryptotanshinone involves activation and translocation of ADAM10 and PKC-α. J Alzheimers Dis. 2011;25(2):245-62. doi: 10.3233/JAD-2011-102085. PMID: 21403388. 11: Poncet N, Guillaume J, Mouchiroud G. Epidermal growth factor receptor transactivation is implicated in IL-6-induced proliferation and ERK1/2 activation in non-transformed prostate epithelial cells. Cell Signal. 2011 Mar;23(3):572-8. doi: 10.1016/j.cellsig.2010.11.009. Epub 2010 Nov 25. PMID: 21111811. 12: Lizama C, Rojas-Benítez D, Antonelli M, Ludwig A, Bustamante-Marín X, Brouwer-Visser J, Moreno RD. TACE/ADAM17 is involved in germ cell apoptosis during rat spermatogenesis. Reproduction. 2010 Aug;140(2):305-17. doi: 10.1530/REP-10-0104. Epub 2010 May 25. PMID: 20501791. 13: Jangouk P, Dehmel T, Meyer Zu Hörste G, Ludwig A, Lehmann HC, Kieseier BC. Involvement of ADAM10 in axonal outgrowth and myelination of the peripheral nerve. Glia. 2009 Dec;57(16):1765-74. doi: 10.1002/glia.20889. PMID: 19455579. 14: Bourd-Boittin K, Basset L, Bonnier D, L'helgoualc'h A, Samson M, Théret N. CX3CL1/fractalkine shedding by human hepatic stellate cells: contribution to chronic inflammation in the liver. J Cell Mol Med. 2009 Aug;13(8A):1526-35. doi: 10.1111/j.1582-4934.2009.00787.x. Epub 2009 May 11. PMID: 19432809; PMCID: PMC3828864. 15: Ahrens I, Ellwanger C, Smith BK, Bassler N, Chen YC, Neudorfer I, Ludwig A, Bode C, Peter K. Selenium supplementation induces metalloproteinase-dependent L-selectin shedding from monocytes. J Leukoc Biol. 2008 Jun;83(6):1388-95. doi: 10.1189/jlb.0707497. Epub 2008 Feb 27. PMID: 18305178. 16: Zhuang S, Kinsey GR, Rasbach K, Schnellmann RG. Heparin-binding epidermal growth factor and Src family kinases in proliferation of renal epithelial cells. Am J Physiol Renal Physiol. 2008 Mar;294(3):F459-68. doi: 10.1152/ajprenal.00473.2007. Epub 2008 Jan 2. PMID: 18171996. 17: Budagian V, Bulanova E, Orinska Z, Duitman E, Brandt K, Ludwig A, Hartmann D, Lemke G, Saftig P, Bulfone-Paus S. Soluble Axl is generated by ADAM10-dependent cleavage and associates with Gas6 in mouse serum. Mol Cell Biol. 2005 Nov;25(21):9324-39. doi: 10.1128/MCB.25.21.9324-9339.2005. Retraction in: Mol Cell Biol. 2011 Mar;31(6):1330. PMID: 16227584; PMCID: PMC1265819. 18: Ludwig A, Hundhausen C, Lambert MH, Broadway N, Andrews RC, Bickett DM, Leesnitzer MA, Becherer JD. Metalloproteinase inhibitors for the disintegrin- like metalloproteinases ADAM10 and ADAM17 that differentially block constitutive and phorbol ester-inducible shedding of cell surface molecules. Comb Chem High Throughput Screen. 2005 Mar;8(2):161-71. doi: 10.2174/1386207053258488. PMID: 15777180. 19: Rabie T, Strehl A, Ludwig A, Nieswandt B. Evidence for a role of ADAM17 (TACE) in the regulation of platelet glycoprotein V. J Biol Chem. 2005 Apr 15;280(15):14462-8. doi: 10.1074/jbc.M500041200. Epub 2005 Feb 3. PMID: 15691827. 20: Budagian V, Bulanova E, Orinska Z, Ludwig A, Rose-John S, Saftig P, Borden EC, Bulfone-Paus S. Natural soluble interleukin-15Ralpha is generated by cleavage that involves the tumor necrosis factor-alpha-converting enzyme (TACE/ADAM17). J Biol Chem. 2004 Sep 24;279(39):40368-75. doi: 10.1074/jbc.M404125200. Epub 2004 Jun 23. Retraction in: J Biol Chem. 2011 Mar 18;286(11):9894. PMID: 15215246. 21: Hundhausen C, Misztela D, Berkhout TA, Broadway N, Saftig P, Reiss K, Hartmann D, Fahrenholz F, Postina R, Matthews V, Kallen KJ, Rose-John S, Ludwig A. The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion. Blood. 2003 Aug 15;102(4):1186-95. doi: 10.1182/blood-2002-12-3775. Epub 2003 Apr 24. PMID: 12714508.

Blocking PSD-93-CX3CL1 Interaction Promotes Phenotypic Polarization Transformation of Microglia During Acute Ischemic Stroke Injury Zhang Q, Cao X, Yang H, Liu X, Lou S, Kong L, Rong L, Shan J, Xu Y Preprint from Research Square, 25 May 2021 DOI: 10.21203/rs.3.rs-538353/v1 PPR: PPR345744 Preprint https://www.researchsquare.com/article/rs-538353/v1