Synonym
BAY 60-6583; BAY-60-6583; BAY60-6583.
IUPAC/Chemical Name
2-({6-amino-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-yl}sulfanyl)acetamide
InChi Key
ZTYHZMAZUWOXNC-UHFFFAOYSA-N
InChi Code
InChI=1S/C19H17N5O2S/c20-7-14-17(12-3-5-13(6-4-12)26-9-11-1-2-11)15(8-21)19(24-18(14)23)27-10-16(22)25/h3-6,11H,1-2,9-10H2,(H2,22,25)(H2,23,24)
SMILES Code
O=C(N)CSC1=NC(N)=C(C#N)C(C2=CC=C(OCC3CC3)C=C2)=C1C#N
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
Biological target:
BAY 60-6583 is an agonist of adenosine A2B receptor with an EC50 of 3 nM.
In vitro activity:
Whether BAY 60-6583 enhances the antitumor activity of CAR T cells in vitro and, if so, whether this is CAR dependent, was evaluated. In the presence of BAY 60-6583, a higher level of cytokine production was observed for anti-CD133 (Figures 3A–C) and anti-HER2 (Supplementary Figure S2A–C) CAR T cells following antigen-specific stimulation, while no changes were observed when the CAR T cells were incubated with non-target tumor cells. Consistently, the tumor cell-killing capacity of CAR T cells was also enhanced when BAY 60-6583 was added and the viability of non-target tumors was not affected (Figure 3D and Supplementary Figure S2D). In addition, BAY 60-6583 treatment also enhanced the proliferative ability of CAR T cells when stimulated by target tumor cells.
Reference: Front Pharmacol. 2021 Mar 12;12:619800. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994267/
In vivo activity:
The functionality of CAR T cells in vivo in the presence of BAY 60-6583 was investigated. NPSG mice were injected with luciferase-expressing MDA-MB-453 cells subcutaneously on day –7, and anti-HER2 CAR T cells were injected intravenously on day 0. After CAR T cell treatment, 20 μg BAY 60-6583 was administered intravenously daily (Figure 5A). BAY 60-6583 injection did not cause any apparent toxicity (Figure 5B). Compared to the vehicle control, daily treatment with 20 μg BAY 60-6583 had a stronger tumor-suppressive effect (Figures 5C,D). Taken together, the data indicate that BAY 60-6583 can enhance the antitumor activity of CAR T cells in tumor models in vivo.
Reference: Front Pharmacol. 2021 Mar 12;12:619800. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994267/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
25.0 |
65.89 |
| DMSO |
56.0 |
147.53 |
| DMSO:PBS (pH 7.2) (1:3) |
0.3 |
0.66 |
| Ethanol |
0.3 |
0.79 |
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
379.44
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. Xu X, Zhu Q, Niu F, Zhang R, Wang Y, Wang W, Sun D, Wang X, Wang A. A2BAR activation attenuates acute lung injury by inhibiting alveolar epithelial cell apoptosis both in vivo and in vitro. Am J Physiol Cell Physiol. 2018 Oct 1;315(4):C558-C570. doi: 10.1152/ajpcell.00294.2017. Epub 2018 Jun 13. PMID: 29898376.
2. Tang J, Zou Y, Li L, Lu F, Xu H, Ren P, Bai F, Niedermann G, Zhu X. BAY 60-6583 Enhances the Antitumor Function of Chimeric Antigen Receptor-Modified T Cells Independent of the Adenosine A2b Receptor. Front Pharmacol. 2021 Mar 12;12:619800. doi: 10.3389/fphar.2021.619800. PMID: 33776765; PMCID: PMC7994267.
In vitro protocol:
1. Xu X, Zhu Q, Niu F, Zhang R, Wang Y, Wang W, Sun D, Wang X, Wang A. A2BAR activation attenuates acute lung injury by inhibiting alveolar epithelial cell apoptosis both in vivo and in vitro. Am J Physiol Cell Physiol. 2018 Oct 1;315(4):C558-C570. doi: 10.1152/ajpcell.00294.2017. Epub 2018 Jun 13. PMID: 29898376.
2. Tang J, Zou Y, Li L, Lu F, Xu H, Ren P, Bai F, Niedermann G, Zhu X. BAY 60-6583 Enhances the Antitumor Function of Chimeric Antigen Receptor-Modified T Cells Independent of the Adenosine A2b Receptor. Front Pharmacol. 2021 Mar 12;12:619800. doi: 10.3389/fphar.2021.619800. PMID: 33776765; PMCID: PMC7994267.
In vivo protocol:
1. Xu X, Zhu Q, Niu F, Zhang R, Wang Y, Wang W, Sun D, Wang X, Wang A. A2BAR activation attenuates acute lung injury by inhibiting alveolar epithelial cell apoptosis both in vivo and in vitro. Am J Physiol Cell Physiol. 2018 Oct 1;315(4):C558-C570. doi: 10.1152/ajpcell.00294.2017. Epub 2018 Jun 13. PMID: 29898376.
2. Tang J, Zou Y, Li L, Lu F, Xu H, Ren P, Bai F, Niedermann G, Zhu X. BAY 60-6583 Enhances the Antitumor Function of Chimeric Antigen Receptor-Modified T Cells Independent of the Adenosine A2b Receptor. Front Pharmacol. 2021 Mar 12;12:619800. doi: 10.3389/fphar.2021.619800. PMID: 33776765; PMCID: PMC7994267.
1: Hayashi M, Inagaki A, Novak I, Matsuda H. The adenosine A2B receptor is involved in anion secretion in human pancreatic duct Capan-1 epithelial cells. Pflugers Arch. 2016 Jul;468(7):1171-81. doi: 10.1007/s00424-016-1806-9. PubMed PMID: 26965147; PubMed Central PMCID: PMC4943985.
2: Wen J, Wang B, Du C, Xu G, Zhang Z, Li Y, Zhang N. A2B Adenosine Receptor Agonist Improves Erectile Function in Diabetic Rats. Tohoku J Exp Med. 2015;237(2):141-8. doi: 10.1620/tjem.237.141. PubMed PMID: 26447087.
3: Nayak S, Khan MA, Wan TC, Pei H, Linden J, Dwinell MR, Geurts AM, Imig JD, Auchampach JA. Characterization of Dahl salt-sensitive rats with genetic disruption of the A2B adenosine receptor gene: implications for A2B adenosine receptor signaling during hypertension. Purinergic Signal. 2015 Dec;11(4):519-31. doi: 10.1007/s11302-015-9470-7. PubMed PMID: 26385692; PubMed Central PMCID: PMC4648794.
4: Sorrentino C, Miele L, Porta A, Pinto A, Morello S. Myeloid-derived suppressor cells contribute to A2B adenosine receptor-induced VEGF production and angiogenesis in a mouse melanoma model. Oncotarget. 2015 Sep 29;6(29):27478-89. doi: 10.18632/oncotarget.4393. PubMed PMID: 26317647; PubMed Central PMCID: PMC4695003.
