GSK199 HCl | CAS#1549811-53-1 | PAD4 inhibitor

MedKoo Cat#: 562523 | Name: GSK199 HCl

Description:

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

GSK199 is a selective PAD4 inhibitor with half-maximum inhibitory concentration (IC50) values, in the absence of calcium, of 200 nM.

Chemical Structure

GSK199 HCl

CAS#1549811-53-1 (HCl)

Theoretical Analysis

MedKoo Cat#: 562523

Name: GSK199 HCl

CAS#: 1549811-53-1 (HCl)

Chemical Formula: C24H29ClN6O2

Exact Mass: 0.0000

Molecular Weight: 468.99

Elemental Analysis: C, 61.47; H, 6.23; Cl, 7.56; N, 17.92; O, 6.82

Price and Availability

Size	Price	Availability
25mg	USD 550.00	2 Weeks
50mg	USD 950.00	2 Weeks
100mg	USD 1,650.00	2 Weeks
1g	USD 5,650.00	2 Weeks

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Related CAS #

1549810-81-2 (free base) 1549811-53-1 (HCl)

Synonym

GSK199; GSK-199; GSK 199; GSK199 HCl; GSK199 hydrochloride;

IUPAC/Chemical Name

(R)-(3-Aminopiperidin-1-yl)(2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone hydrochloride

InChi Key

KRGMIOKDGHBYQE-UNTBIKODSA-N

InChi Code

InChI=1S/C24H28N6O2.ClH/c1-4-30-19(12-15-7-5-9-26-22(15)30)23-27-18-11-16(13-20(32-3)21(18)28(23)2)24(31)29-10-6-8-17(25)14-29;/h5,7,9,11-13,17H,4,6,8,10,14,25H2,1-3H3;1H/t17-;/m1./s1

SMILES Code

O=C(N1C[C@H](N)CCC1)C2=CC(OC)=C3N(C)C(C4=CC5=CC=CN=C5N4CC)=NC3=C2.[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:

GSK199 is a reversible and selective PAD4 inhibitor with an IC50 of 200 nM in the absence of calcium.

In vitro activity:

Consistently, immunoblot analysis of total protein extracts from HCoV-OC43-infected MRC-5 cells treated with GSK199 showed a dramatic downregulation of OC43 NP protein expression levels in comparison with vehicle-treated infected cells (Fig. 2E). Reference: Antiviral Res. 2022 Apr;200:105278. https://pubmed.ncbi.nlm.nih.gov/35288208/

In vivo activity:

Remarkably, treatment with 30 mg/kg b.i.d. GSK199 resulted in the elimination of C3 deposition in both compartments (P < 0·05), while treatment with 10 or 30 mg/kg q.d. GSK199 also reduced C3 deposition significantly (P < 0·05). Similar to clinical disease activity, treatment with saline alone resulted in decreased C3 deposition in the synovium and cartilage relative to untreated mice. These results indicate that GSK199 treatment blocks joint destruction and reduces C3 deposition in the joints of mice with CIA. Reference: Clin Exp Immunol. 2017 May;188(2):263-274. https://pubmed.ncbi.nlm.nih.gov/28128853/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	63.97
	DMSO	30.0	63.97
	Ethanol	30.0	63.97
	PBS (pH 7.2)	10.0	21.32

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 468.99 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. Pasquero S, Gugliesi F, Griffante G, Dell'Oste V, Biolatti M, Albano C, Bajetto G, Delbue S, Signorini L, Dolci M, Landolfo S, De Andrea M. Novel antiviral activity of PAD inhibitors against human beta-coronaviruses HCoV-OC43 and SARS-CoV-2. Antiviral Res. 2022 Apr;200:105278. doi: 10.1016/j.antiviral.2022.105278. Epub 2022 Mar 11. PMID: 35288208; PMCID: PMC8915624. 2. Martín Monreal MT, Rebak AS, Massarenti L, Mondal S, Šenolt L, Ødum N, Nielsen ML, Thompson PR, Nielsen CH, Damgaard D. Applicability of Small-Molecule Inhibitors in the Study of Peptidyl Arginine Deiminase 2 (PAD2) and PAD4. Front Immunol. 2021 Oct 19;12:716250. doi: 10.3389/fimmu.2021.716250. PMID: 34737738; PMCID: PMC8560728. 3. Willis VC, Banda NK, Cordova KN, Chandra PE, Robinson WH, Cooper DC, Lugo D, Mehta G, Taylor S, Tak PP, Prinjha RK, Lewis HD, Holers VM. Protein arginine deiminase 4 inhibition is sufficient for the amelioration of collagen-induced arthritis. Clin Exp Immunol. 2017 May;188(2):263-274. doi: 10.1111/cei.12932. Epub 2017 Mar 9. PMID: 28128853; PMCID: PMC5383440.

In vitro protocol:

In vivo protocol:

1. Willis VC, Banda NK, Cordova KN, Chandra PE, Robinson WH, Cooper DC, Lugo D, Mehta G, Taylor S, Tak PP, Prinjha RK, Lewis HD, Holers VM. Protein arginine deiminase 4 inhibition is sufficient for the amelioration of collagen-induced arthritis. Clin Exp Immunol. 2017 May;188(2):263-274. doi: 10.1111/cei.12932. Epub 2017 Mar 9. PMID: 28128853; PMCID: PMC5383440.

1: Willis VC, Banda NK, Cordova KN, Chandra PE, Robinson WH, Cooper DC, Lugo D, Mehta G, Taylor S, Tak PP, Prinjha RK, Lewis HD, Holers VM. Protein arginine deiminase 4 inhibition is sufficient for the amelioration of collagen-induced arthritis. Clin Exp Immunol. 2017 May;188(2):263-274. doi: 10.1111/cei.12932. Epub 2017 Mar 9. PubMed PMID: 28128853; PubMed Central PMCID: PMC5383440. 2: Lewis HD, Liddle J, Coote JE, Atkinson SJ, Barker MD, Bax BD, Bicker KL, Bingham RP, Campbell M, Chen YH, Chung CW, Craggs PD, Davis RP, Eberhard D, Joberty G, Lind KE, Locke K, Maller C, Martinod K, Patten C, Polyakova O, Rise CE, Rüdiger M, Sheppard RJ, Slade DJ, Thomas P, Thorpe J, Yao G, Drewes G, Wagner DD, Thompson PR, Prinjha RK, Wilson DM. Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation. Nat Chem Biol. 2015 Mar;11(3):189-91. doi: 10.1038/nchembio.1735. Epub 2015 Jan 26. PubMed PMID: 25622091; PubMed Central PMCID: PMC4397581. 3: Slade DJ, Fang P, Dreyton CJ, Zhang Y, Fuhrmann J, Rempel D, Bax BD, Coonrod SA, Lewis HD, Guo M, Gross ML, Thompson PR. Protein arginine deiminase 2 binds calcium in an ordered fashion: implications for inhibitor design. ACS Chem Biol. 2015 Apr 17;10(4):1043-53. doi: 10.1021/cb500933j. Epub 2015 Jan 26. PubMed PMID: 25621824; PubMed Central PMCID: PMC4569063.