Synonym
R112; R112; R 112.
IUPAC/Chemical Name
3,3'-((5-fluoropyrimidine-2,4-diyl)bis(azanediyl))diphenol
InChi Key
TVKGTSHBQZEFEE-UHFFFAOYSA-N
InChi Code
InChI=1S/C16H13FN4O2/c17-14-9-18-16(20-11-4-2-6-13(23)8-11)21-15(14)19-10-3-1-5-12(22)7-10/h1-9,22-23H,(H2,18,19,20,21)
SMILES Code
FC1=CN=C(NC2=CC(O)=CC=C2)N=C1NC3=CC(O)=CC=C3
Appearance
White to off white 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 soluble in water.
Shelf Life
>5 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
Biological target:
R112 is an inhibitor of spleen tyrosine kinase (Syk; IC50 = 226 nM in cultured human mast cells) that acts in an ATP-competitive and reversible manner (Ki = 96 nM).
In vitro activity:
Activation of the IgE receptor, FcvarepsilonRI, in mast cells is the key mechanism initiating and propagating pathophysiological responses in allergic rhinitis. Unlike other mast cell inhibitors, R112 was able to completely inhibit all three IgE-induced mast cell functions: degranulation, lipid mediator production, and cytokine production.
Reference: J Allergy Clin Immunol. 2006 Sep;118(3):749-55. https://pubmed.ncbi.nlm.nih.gov/16950297/
In vivo activity:
R112 significantly reduced the Global Symptom Complex (GSC) scale compared with placeboin a study of 319 people. Each individual symptom combined to form the GSC was also significantly improved in the R112 group compared with control. As early as 45 minutes after dosing, R112 showed a significant improvement in symptoms over placebo, and the duration exceeded 4 hours.
Reference: J Allergy Clin Immunol. 2005 Apr;115(4):791-6. https://pubmed.ncbi.nlm.nih.gov/15806000/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
30.0 |
96.10 |
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
312.30
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. Rossi AB, Herlaar E, Braselmann S, Huynh S, Taylor V, Frances R, Issakani SD, Argade A, Singh R, Payan DG, Masuda ES. Identification of the Syk kinase inhibitor R112 by a human mast cell screen. J Allergy Clin Immunol. 2006 Sep;118(3):749-55. doi: 10.1016/j.jaci.2006.05.023. Epub 2006 Jul 28. PMID: 16950297.
2. Guyer BJ, Shimamoto SR, Bradhurst AL, Grossbard EB, Dreskin SC, Nelson HS. Mast cell inhibitor R112 is well tolerated and affects prostaglandin D2 but not other mediators, symptoms, or nasal volumes in a nasal challenge model of allergic rhinitis. Allergy Asthma Proc. 2006 May-Jun;27(3):208-13. doi: 10.2500/aap.2006.27.2861. PMID: 16913263.
3. Meltzer EO, Berkowitz RB, Grossbard EB. An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment. J Allergy Clin Immunol. 2005 Apr;115(4):791-6. doi: 10.1016/j.jaci.2005.01.040. PMID: 15806000.
In vitro protocol:
1. Rossi AB, Herlaar E, Braselmann S, Huynh S, Taylor V, Frances R, Issakani SD, Argade A, Singh R, Payan DG, Masuda ES. Identification of the Syk kinase inhibitor R112 by a human mast cell screen. J Allergy Clin Immunol. 2006 Sep;118(3):749-55. doi: 10.1016/j.jaci.2006.05.023. Epub 2006 Jul 28. PMID: 16950297.
In vivo protocol:
1. Guyer BJ, Shimamoto SR, Bradhurst AL, Grossbard EB, Dreskin SC, Nelson HS. Mast cell inhibitor R112 is well tolerated and affects prostaglandin D2 but not other mediators, symptoms, or nasal volumes in a nasal challenge model of allergic rhinitis. Allergy Asthma Proc. 2006 May-Jun;27(3):208-13. doi: 10.2500/aap.2006.27.2861. PMID: 16913263.
2. Meltzer EO, Berkowitz RB, Grossbard EB. An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment. J Allergy Clin Immunol. 2005 Apr;115(4):791-6. doi: 10.1016/j.jaci.2005.01.040. PMID: 15806000.
1: Rossi AB, Herlaar E, Braselmann S, Huynh S, Taylor V, Frances R, Issakani SD, Argade A, Singh R, Payan DG, Masuda ES. Identification of the Syk kinase inhibitor R112 by a human mast cell screen. J Allergy Clin Immunol. 2006 Sep;118(3):749-55. Epub 2006 Jul 28. PubMed PMID: 16950297.
2: Guyer BJ, Shimamoto SR, Bradhurst AL, Grossbard EB, Dreskin SC, Nelson HS. Mast cell inhibitor R112 is well tolerated and affects prostaglandin D2 but not other mediators, symptoms, or nasal volumes in a nasal challenge model of allergic rhinitis. Allergy Asthma Proc. 2006 May-Jun;27(3):208-13. PubMed PMID: 16913263.
3: Meltzer EO, Berkowitz RB, Grossbard EB. An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment. J Allergy Clin Immunol. 2005 Apr;115(4):791-6. PubMed PMID: 15806000.
4: Kang AK, Jenkins DJ, Wolever TM, Huff MW, Maguire GF, Connelly PW, Hegele RA. Apolipoprotein E R112; R251G: a carboxy-terminal variant found in patients with hyperlipidemia and coronary heart disease. Mutat Res. 1997 Sep;382(1-2):57-65. PubMed PMID: 9360638.
