WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H562097
CAS#: 1423186-80-4 (active metabolite)
Description: 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.
Hodoodo Cat#: H562097
Name: GSK2983559-AM
CAS#: 1423186-80-4 (active metabolite)
Chemical Formula: C21H22N4O4S2
Exact Mass: 458.11
Molecular Weight: 458.550
Elemental Analysis: C, 55.01; H, 4.84; N, 12.22; O, 13.96; S, 13.98
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:
| 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 | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 5.0 | 9.28 |
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. 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. |
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.
