GSK2983559-AM | RIPK2-IN-1 | CAS#1423186-80-4 | RIP2 kinase inhibitor

MedKoo Cat#: 562097 | Name: GSK2983559-AM

Description:

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

GSK2983559-AM, also known as GSK2983559 active metabolite, is an active metabolite of GSK2983559, also known as RIPK2-IN-1, is a potent and selective inhibitor of receptor interacting protein-2 (RIP2) kinase.

Chemical Structure

GSK2983559-AM

CAS#1423186-80-4 (active metabolite)

Theoretical Analysis

MedKoo Cat#: 562097

Name: GSK2983559-AM

CAS#: 1423186-80-4 (active metabolite)

Chemical Formula: C21H22N4O4S2

Exact Mass: 458.1082

Molecular Weight: 458.55

Elemental Analysis: C, 55.01; H, 4.84; N, 12.22; O, 13.96; S, 13.98

Price and Availability

Size	Price	Availability
10mg	USD 190.00	Ready to ship
25mg	USD 350.00	Ready to ship
50mg	USD 650.00	Ready to ship
100mg	USD 1,050.00	Ready to ship
200mg	USD 1,850.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 3,650.00	Ready to ship
2g	USD 6,450.00	Ready to ship

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Related CAS #

1579965-12-0 (free acid) 1423186-80-4 (active metabolite)

Synonym

GSK2983559-AM, GSK2983559-active metabolite; GSK2983559; GSK-2983559 ; GSK 2983559 ; RIPK2-IN-1; RIPK2 IN 1; RIPK2IN1; RIPK2 inhibitor-1; RIPK2 inhibitor 1;

IUPAC/Chemical Name

2-[[4-(5-Benzothiazolylamino)-6-[(1,1-dimethylethyl)sulfonyl]-7-quinazolinyl]oxy]ethanol

InChi Key

UHDOJINBFLDQJM-UHFFFAOYSA-N

InChi Code

InChI=1S/C21H22N4O4S2/c1-21(2,3)31(27,28)19-9-14-15(10-17(19)29-7-6-26)22-11-23-20(14)25-13-4-5-18-16(8-13)24-12-30-18/h4-5,8-12,26H,6-7H2,1-3H3,(H,22,23,25)

SMILES Code

O=S(C1=CC2=C(NC3=CC=C(SC=N4)C4=C3)N=CN=C2C=C1OCCO)(C(C)(C)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

Certificate of Analysis

View CoA: current batch, Lot# C9R06B27

QC Data

View QC data: current batch, Lot# C9R06B27

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

GSK2983559 (compound 5) is a potent, specific and oral bioavailable receptor interacting protein 2 (RIP2) kinase inhibitor, which has excellent activity in blocking many proinflammatory cytokine responses in vivo and in human inflammatory bowel disease explant samples.

In vitro activity:

GSK2983559-AM (compound 5) exhibited a coherent pharmacological profile across biochemical, cellular, and tissue-based functional assays. Inhibitor 5 was potent in both rat and human RIP2 binding fluorescence polarization (FP) assays as well a human kinase activity assay (ADP-Glo) (Table 6). Cellular activity was demonstrated in HEK293 cells overexpressing NOD2 and primary human monocytes isolated from the blood of normal healthy volunteers as well as in human whole blood. Inhibitor 5 potently and dose dependently inhibited MDP-stimulated IL-8 production in HEK293 cells and TNFα production in monocytes, with IC50 values of 4 and 13 nM, respectively. Compound 5 demonstrated a slight reduction in potency when profiled in a similar MDP-induced TNFα production assay in human whole blood (IC50 = 26 nM) which can be attributed to plasma protein binding. Free fraction was similar across species (Table 7). Reference: J Med Chem. 2019 Jul 25;62(14):6482-6494. https://doi.org/10.1021/acs.jmedchem.9b00575

In vivo activity:

GSK2983559-AM (inhibitor 5) had an acceptable low dose pharmacokinetic profile in rat, dog, and minipig. Reasonable clearance and volume of distribution were observed in all species, albeit with a relatively short terminal half-life. Rat and dog demonstrated moderate to good oral bioavailability, respectively (Table 1). However, high dose safety assessment studies in rats resulted in nondose linearity, precluding adequate toxicology evaluation at the highest dose (Table 2). This lack of dose linearity is believed to be a consequence of the poor solubility in fasted state simulated intestinal fluid (FaSSIF) associated with compound 5 (4 μg/mL), likely leading to compound precipitation in the gastrointestinal (GI) tract as dose increased. Reference: J Med Chem. 2019 Jul 25;62(14):6482-6494. https://doi.org/10.1021/acs.jmedchem.9b00575

	Solvent	mg/mL	mM
Solubility
	DMSO	5.0	9.28

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 458.55 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:

In vitro protocol:

1. Haile PA, Casillas LN, Votta BJ, Wang GZ, Charnley AK, Dong X, Bury MJ, Romano JJ, Mehlmann JF, King BW, Erhard KF, Hanning CR, Lipshutz DB, Desai BM, Capriotti CA, Schaeffer MC, Berger SB, Mahajan MK, Reilly MA, Nagilla R, Rivera EJ, Sun HH, Kenna JK, Beal AM, Ouellette MT, Kelly M, Stemp G, Convery MA, Vossenkämper A, MacDonald TT, Gough PJ, Bertin J, Marquis RW. Discovery of a First-in-Class Receptor Interacting Protein 2 (RIP2) Kinase Specific Clinical Candidate, 2-((4-(Benzo[d]thiazol-5-ylamino)-6-(tert-butylsulfonyl)quinazolin-7-yl)oxy)ethyl Dihydrogen Phosphate, for the Treatment of Inflammatory Diseases. J Med Chem. 2019 Jul 25;62(14):6482-6494. doi: 10.1021/acs.jmedchem.9b00575. Epub 2019 Jul 2. PMID: 31265286.

In vivo protocol:

1. Sheridan C. Publisher Correction: Death by inflammation: drug makers chase the master controller. Nat Biotechnol. 2019;37(4):480. doi:10.1038/s41587-019-0082-6.