Synonym
AZ1, AZ 1 AZ-1; TX4; TX-4; TX 4; AZD-5904; AZD 5904; AZD5904.
IUPAC/Chemical Name
(S)-3-((tetrahydrofuran-2-yl)methyl)-2-thioxo-1,2,3,7-tetrahydro-6H-purin-6-one
InChi Key
RSPDBEVKURKEII-LURJTMIESA-N
InChi Code
InChI=1S/C10H12N4O2S/c15-9-7-8(12-5-11-7)14(10(17)13-9)4-6-2-1-3-16-6/h5-6H,1-4H2,(H,11,12)(H,13,15,17)/t6-/m0/s1
SMILES Code
O=C1NC(N(C[C@H]2OCCC2)C3=C1NC=N3)=S
Appearance
Beige to light yellow 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 in water
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
Note: Chemical structure was from 1: Ruggeri RB, Buckbinder L, Bagley SW, Carpino PA, Conn EL, Dowling MS, Fernando DP, Jiao W, Kung DW, Orr ST, Qi Y, Rocke BN, Smith A, Warmus JS, Zhang Y, Bowles D, Widlicka DW, Eng H, Ryder T, Sharma R, Wolford A, Okerberg C, Walters K, Maurer TS, Zhang Y, Bonin PD, Spath SN, Xing G, Hepworth D, Ahn K, Kalgutkar AS. Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases. J Med Chem. 2015 Oct 28. [Epubahead of print] PubMed PMID: 26509551.
Biological target:
AZD5904 is an irreversible inhibitor of human Myeloperoxidase (MPO) with an IC50 of 140 nM and has similar potency in mouse and rat.
In vitro activity:
Overall 3 mM AZD5904 resulted in a significant increase in sperm penetration (Fig. 2B and C; P¼ 0.003). After 24-h incubation, 3 mM AZD5904 increased sperm penetration in 4/11 (36.4%) samples, whereas 7/11 (63.4%) showed no response at 24 h, but none showed a negative effect (Fig. 2D). A significant overall increase in sperm function was also seen (Fig. 2E and F; P ¼ 0.039). The results also appeared to be reproducible. One patient submitted a sample for research on three separate occasions. Although semen characteristics results were variable, each sample consistently showed improved sperm function with 3 mM AZD5904 (Supplementary Fig. S2).
Reference: Hum Reprod. 2021 Feb 18;36(3):560-570. https://pubmed.ncbi.nlm.nih.gov/33393586/
In vivo activity:
High-fat diet feeding reduced insulin sensitivity, as indicated by a diminished glucose infusion rate required to maintain euglycemia during the insulin clamp (Fig. 1). Continuously infusing AZD5904 during the 2 wk of HFD feeding did not prevent the development of metabolic insulin resistance. In control rats, insulin increased the MBV within 60 min of initiating the insulin clamp, and the expanded volume persisted at 120 min. Two weeks of HFD feeding totally blocked insulin’s action to recruit muscle microvasculature (Fig. 2 and Table 2) throughout the 120 min of insulin infusion (P < 0.001). The two weeks of subcutaneous infusion of AZD5904 prevented the effect of HFD on microvascular insulin responsiveness. MFV, also measured by contrast ultrasound, was not affected by insulin treatment and was not different between the three experimental groups. MBF (the product of MBV × MFV) increased in control and HFD+AZD5904-treated rats but not in HFD alone (P < 0.01); i.e., muscle microvascular perfusion was preserved in the drug-treated animals.
Reference: Am J Physiol Endocrinol Metab. 2019 Dec 1;317(6):E1063-E1069. https://pubmed.ncbi.nlm.nih.gov/31593502/
|
Solvent |
mg/mL |
mM |
| Solubility |
| dmso |
22.7 |
90.09 |
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
252.29
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. Campbell MJ, Sucquart IE, Whittaker A, Sanganee HJ, Barratt CLR, Martins da Silva SJ. Myeloperoxidase inhibitor AZD5904 enhances human sperm function in vitro. Hum Reprod. 2021 Feb 18;36(3):560-570. doi: 10.1093/humrep/deaa328. PMID: 33393586.
2. Chai W, Aylor K, Liu Z, Gan LM, Michaëlsson E, Barrett E. Inhibiting myeloperoxidase prevents onset and reverses established high-fat diet-induced microvascular insulin resistance. Am J Physiol Endocrinol Metab. 2019 Dec 1;317(6):E1063-E1069. doi: 10.1152/ajpendo.00203.2019. Epub 2019 Oct 8. PMID: 31593502.
In vitro protocol:
1. Campbell MJ, Sucquart IE, Whittaker A, Sanganee HJ, Barratt CLR, Martins da Silva SJ. Myeloperoxidase inhibitor AZD5904 enhances human sperm function in vitro. Hum Reprod. 2021 Feb 18;36(3):560-570. doi: 10.1093/humrep/deaa328. PMID: 33393586.
In vivo protocol:
1. Chai W, Aylor K, Liu Z, Gan LM, Michaëlsson E, Barrett E. Inhibiting myeloperoxidase prevents onset and reverses established high-fat diet-induced microvascular insulin resistance. Am J Physiol Endocrinol Metab. 2019 Dec 1;317(6):E1063-E1069. doi: 10.1152/ajpendo.00203.2019. Epub 2019 Oct 8. PMID: 31593502.
1. Ruggeri RB, Buckbinder L, Bagley SW, Carpino PA, Conn EL, Dowling MS, Fernando DP, Jiao W, Kung DW, Orr ST, Qi Y, Rocke BN, Smith A, Warmus JS, Zhang Y, Bowles D, Widlicka DW, Eng H, Ryder T, Sharma R, Wolford A, Okerberg C, Walters K, Maurer TS, Zhang Y, Bonin PD, Spath SN, Xing G, Hepworth D, Ahn K, Kalgutkar AS. Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases. J Med Chem. 2015 Oct 28. [Epubahead of print] PubMed PMID: 26509551.
