GSK583
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MedKoo CAT#: 526612

CAS#: 1346547-00-9

Description: GSK583 is a Highly Potent and Selective Inhibitor of RIP2 Kinase (RIP2K bing IC50=5 nM; rat in vivo PD IC50 = 50 nM). RIP2 kinase is a central component of the innate immune system and enables downstream signaling following activation of the pattern recognition receptors NOD1 and NOD2, leading to the production of inflammatory cytokines.

Chemical Structure

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GSK583
CAS# 1346547-00-9
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 526612
Name: GSK583
CAS#: 1346547-00-9
Chemical Formula: C20H19FN4O2S
Exact Mass: 398.12
Molecular Weight: 398.456
Elemental Analysis: C, 60.29; H, 4.81; F, 4.77; N, 14.06; O, 8.03; S, 8.05

Price and Availability

Size Price Availability Quantity
25mg USD 450
50mg USD 750
100mg USD 1250
200mg USD 1950
500mg USD 2950 2 Weeks
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Synonym: GSK583; GSK 583; GSK-583.

IUPAC/Chemical Name: 6‑(tert-Butylsulfonyl)‑N‑(5-fluoro‑1H‑indazol-3-yl)quinolin-4-amine

InChi Key: XLOGLWKOHPIJLV-UHFFFAOYSA-N

InChi Code: InChI=1S/C20H19FN4O2S/c1-20(2,3)28(26,27)13-5-7-16-14(11-13)17(8-9-22-16)23-19-15-10-12(21)4-6-18(15)24-25-19/h4-11H,1-3H3,(H2,22,23,24,25)

SMILES Code: FC1=CC2=C(NN=C2NC3=CC=NC4=CC=C(S(=O)(C(C)(C)C)=O)C=C34)C=C1

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, not in water

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: GSK583 is a highly potent, orally active and selective inhibitor of RIP2 Kinase, with IC50 of 5 nM. GSK583 inhibits both TNF-α and IL-6 production with an IC50 value of 200 nM.
In vitro activity: This study presents, herein, the discovery and pharmacological characterization of GSK583, a next-generation RIP2 inhibitor possessing exquisite selectivity and potency. Reference: J Med Chem. 2016 May 26;59(10):4867-80. https://pubmed.ncbi.nlm.nih.gov/27109867/
In vivo activity: In addition, mice subjected to either ML130 or GSK583 administration exhibited a significant reduction in brain water content, neurological deficit scores, and percentage of right turns in the corner-turning experiment compared with the DMSO-treated group (Fig. 3b). Reference: J Neuroinflammation. 2020 Dec 1;17(1):364. https://pubmed.ncbi.nlm.nih.gov/33261639/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 30.0 75.29
DMF:PBS (pH 7.2) (1:9) 0.1 0.25
DMSO 73.0 183.07
Ethanol 18.0 45.14

Preparing Stock Solutions

The following data is based on the product molecular weight 398.46 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. Haile PA, Casillas LN, Bury MJ, Mehlmann JF, Singhaus R Jr, Charnley AK, Hughes TV, DeMartino MP, Wang GZ, Romano JJ, Dong X, Plotnikov NV, Lakdawala AS, Convery MA, Votta BJ, Lipshutz DB, Desai BM, Swift B, Capriotti CA, Berger SB, Mahajan MK, Reilly MA, Rivera EJ, Sun HH, Nagilla R, LePage C, Ouellette MT, Totoritis RD, Donovan BT, Brown BS, Chaudhary KW, Gough PJ, Bertin J, Marquis RW. Identification of Quinoline-Based RIP2 Kinase Inhibitors with an Improved Therapeutic Index to the hERG Ion Channel. ACS Med Chem Lett. 2018 Sep 26;9(10):1039-1044. doi: 10.1021/acsmedchemlett.8b00344. Erratum in: ACS Med Chem Lett. 2020 Jun 02;11(6):1353. PMID: 30344914; PMCID: PMC6187414. 2. Haile PA, Votta BJ, Marquis RW, Bury MJ, Mehlmann JF, Singhaus R Jr, Charnley AK, Lakdawala AS, Convery MA, Lipshutz DB, Desai BM, Swift B, Capriotti CA, Berger SB, Mahajan MK, Reilly MA, Rivera EJ, Sun HH, Nagilla R, Beal AM, Finger JN, Cook MN, King BW, Ouellette MT, Totoritis RD, Pierdomenico M, Negroni A, Stronati L, Cucchiara S, Ziółkowski B, Vossenkämper A, MacDonald TT, Gough PJ, Bertin J, Casillas LN. The Identification and Pharmacological Characterization of 6-(tert-Butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine (GSK583), a Highly Potent and Selective Inhibitor of RIP2 Kinase. J Med Chem. 2016 May 26;59(10):4867-80. doi: 10.1021/acs.jmedchem.6b00211. Epub 2016 May 4. PMID: 27109867. 3. Wang M, Ye X, Hu J, Zhao Q, Lv B, Ma W, Wang W, Yin H, Hao Q, Zhou C, Zhang T, Wu W, Wang Y, Zhou M, Zhang CH, Cui G. NOD1/RIP2 signalling enhances the microglia-driven inflammatory response and undergoes crosstalk with inflammatory cytokines to exacerbate brain damage following intracerebral haemorrhage in mice. J Neuroinflammation. 2020 Dec 1;17(1):364. doi: 10.1186/s12974-020-02015-9. PMID: 33261639; PMCID: PMC7708246.
In vitro protocol: 1. Haile PA, Casillas LN, Bury MJ, Mehlmann JF, Singhaus R Jr, Charnley AK, Hughes TV, DeMartino MP, Wang GZ, Romano JJ, Dong X, Plotnikov NV, Lakdawala AS, Convery MA, Votta BJ, Lipshutz DB, Desai BM, Swift B, Capriotti CA, Berger SB, Mahajan MK, Reilly MA, Rivera EJ, Sun HH, Nagilla R, LePage C, Ouellette MT, Totoritis RD, Donovan BT, Brown BS, Chaudhary KW, Gough PJ, Bertin J, Marquis RW. Identification of Quinoline-Based RIP2 Kinase Inhibitors with an Improved Therapeutic Index to the hERG Ion Channel. ACS Med Chem Lett. 2018 Sep 26;9(10):1039-1044. doi: 10.1021/acsmedchemlett.8b00344. Erratum in: ACS Med Chem Lett. 2020 Jun 02;11(6):1353. PMID: 30344914; PMCID: PMC6187414. 2. Haile PA, Votta BJ, Marquis RW, Bury MJ, Mehlmann JF, Singhaus R Jr, Charnley AK, Lakdawala AS, Convery MA, Lipshutz DB, Desai BM, Swift B, Capriotti CA, Berger SB, Mahajan MK, Reilly MA, Rivera EJ, Sun HH, Nagilla R, Beal AM, Finger JN, Cook MN, King BW, Ouellette MT, Totoritis RD, Pierdomenico M, Negroni A, Stronati L, Cucchiara S, Ziółkowski B, Vossenkämper A, MacDonald TT, Gough PJ, Bertin J, Casillas LN. The Identification and Pharmacological Characterization of 6-(tert-Butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine (GSK583), a Highly Potent and Selective Inhibitor of RIP2 Kinase. J Med Chem. 2016 May 26;59(10):4867-80. doi: 10.1021/acs.jmedchem.6b00211. Epub 2016 May 4. PMID: 27109867.
In vivo protocol: 1. Wang M, Ye X, Hu J, Zhao Q, Lv B, Ma W, Wang W, Yin H, Hao Q, Zhou C, Zhang T, Wu W, Wang Y, Zhou M, Zhang CH, Cui G. NOD1/RIP2 signalling enhances the microglia-driven inflammatory response and undergoes crosstalk with inflammatory cytokines to exacerbate brain damage following intracerebral haemorrhage in mice. J Neuroinflammation. 2020 Dec 1;17(1):364. doi: 10.1186/s12974-020-02015-9. PMID: 33261639; PMCID: PMC7708246. 2. Haile PA, Casillas LN, Bury MJ, Mehlmann JF, Singhaus R Jr, Charnley AK, Hughes TV, DeMartino MP, Wang GZ, Romano JJ, Dong X, Plotnikov NV, Lakdawala AS, Convery MA, Votta BJ, Lipshutz DB, Desai BM, Swift B, Capriotti CA, Berger SB, Mahajan MK, Reilly MA, Rivera EJ, Sun HH, Nagilla R, LePage C, Ouellette MT, Totoritis RD, Donovan BT, Brown BS, Chaudhary KW, Gough PJ, Bertin J, Marquis RW. Identification of Quinoline-Based RIP2 Kinase Inhibitors with an Improved Therapeutic Index to the hERG Ion Channel. ACS Med Chem Lett. 2018 Sep 26;9(10):1039-1044. doi: 10.1021/acsmedchemlett.8b00344. Erratum in: ACS Med Chem Lett. 2020 Jun 02;11(6):1353. PMID: 30344914; PMCID: PMC6187414.

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The Identification and Pharmacological Characterization of 6-(tert-Butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine (GSK583), a Highly Potent and Selective Inhibitor of RIP2 Kinase. Pamela A. Haile, Bartholomew J. Votta, Robert W. Marquis, Michael J. Bury, John F. Mehlmann, Robert Singhaus Jr., Adam K. Charnley, Ami S. Lakdawala, Máire A. Convery, David B. Lipshutz, Biva M. Desai, Barbara Swift, Carol A. Capriotti, Scott B. Berger, Mukesh K. Majahan, Michael A. Reilly, Elizabeth J. Rivera, Helen H. Sun, Rakesh Nagilla, Allison M. Beal, Joshua N. Finger, Michael N. Cook, Bryan W. King, Michael T. Ouellette, Rachel D. Totoritis, Maria Pierdomenico, Anna Negroni, Laura Stronati, Salvatore Cucchiara, Bartłomiej Ziółkowski, Anna Vossenkämper, Thomas T. MacDonald, Peter J. Gough, John Bertin, and Linda N. Casillas Publication Date (Web): April 25, 2016 (Article) DOI: 10.1021/acs.jmedchem.6b00211