Synonym
AZ-10397767; AZ 10397767; AZ10397767.
IUPAC/Chemical Name
5-[[(3-Chloro-2-fluorophenyl)methyl]thio]-7-[[(1R)-2-hydroxy-1-methylethyl]amino]thiazolo[4,5-d]pyrimidin-2(3H)-one
InChi Key
KHTUORKUWBDRBX-SSDOTTSWSA-N
InChi Code
InChI=1S/C15H14ClFN4O2S2/c1-7(5-22)18-12-11-13(21-15(23)25-11)20-14(19-12)24-6-8-3-2-4-9(16)10(8)17/h2-4,7,22H,5-6H2,1H3,(H2,18,19,20,21,23)/t7-/m1/s1
SMILES Code
O=C1SC2=C(N[C@H](C)CO)N=C(SCC3=CC=CC(Cl)=C3F)N=C2N1
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:
Potent CXCR2 antagonist.
In vitro activity:
The addition of AZ10397767, used at a final concentration of 20 nM in order to exercise its selectivity for the CXCR2 receptor increased the potency of 5-FU-induced cytotoxicity in PC3 cells. Non-linear regression analysis of the data confirmed that the inhibition of CXCR2 signaling enhanced the potency of 5-FU by 3.8-fold, increasing the calculated IC30 value from 4.2 µM to 1.1 µM (n = 4).
Reference: PLoS One. 2012; 7(5): e36545. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348872/
In vivo activity:
The mean tumor volume in AZ10397767-treated tumors started to diverge from control tumor volume by day 21 (11 days after commencement of antagonist dosing). At day 25 there was a significant difference (p < 0.05) in the volume of AZ10397767-treated compared to control tumors (Fig. 5a), this difference was more pronounced over the next several days and by day 31 AZ10397767-treated tumors were 36% smaller than their control counterparts (p < 0.01; Fig. 6a). Gr-1-positive neutrophils were abundant and distributed throughout A549 xenograft control mouse tumors when analyzed by immunohistochemistry (Fig. 5b). However, administration of AZ10397767 significantly (p < 0.01) reduced the number of tumor-infiltrating neutrophils compared to mice receiving vehicle control (Fig. 5b).
Reference: Int J Cancer. 2011 Aug 15;129(4):847-58. https://pubmed.ncbi.nlm.nih.gov/21328342/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
40.1 |
100.01 |
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
400.87
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. Wilson C, Maxwell PJ, Longley DB, Wilson RH, Johnston PG, Waugh DJ. Constitutive and treatment-induced CXCL8-signalling selectively modulates the efficacy of anti-metabolite therapeutics in metastatic prostate cancer. PLoS One. 2012;7(5):e36545. doi: 10.1371/journal.pone.0036545. Epub 2012 May 9. PMID: 22590561; PMCID: PMC3348872.
2. Tazzyman S, Barry ST, Ashton S, Wood P, Blakey D, Lewis CE, Murdoch C. Inhibition of neutrophil infiltration into A549 lung tumors in vitro and in vivo using a CXCR2-specific antagonist is associated with reduced tumor growth. Int J Cancer. 2011 Aug 15;129(4):847-58. doi: 10.1002/ijc.25987. Epub 2011 Apr 13. PMID: 21328342.
In vitro protocol:
1. Wilson C, Maxwell PJ, Longley DB, Wilson RH, Johnston PG, Waugh DJ. Constitutive and treatment-induced CXCL8-signalling selectively modulates the efficacy of anti-metabolite therapeutics in metastatic prostate cancer. PLoS One. 2012;7(5):e36545. doi: 10.1371/journal.pone.0036545. Epub 2012 May 9. PMID: 22590561; PMCID: PMC3348872.
2. Tazzyman S, Barry ST, Ashton S, Wood P, Blakey D, Lewis CE, Murdoch C. Inhibition of neutrophil infiltration into A549 lung tumors in vitro and in vivo using a CXCR2-specific antagonist is associated with reduced tumor growth. Int J Cancer. 2011 Aug 15;129(4):847-58. doi: 10.1002/ijc.25987. Epub 2011 Apr 13. PMID: 21328342.
In vivo protocol:
1. Tazzyman S, Barry ST, Ashton S, Wood P, Blakey D, Lewis CE, Murdoch C. Inhibition of neutrophil infiltration into A549 lung tumors in vitro and in vivo using a CXCR2-specific antagonist is associated with reduced tumor growth. Int J Cancer. 2011 Aug 15;129(4):847-58. doi: 10.1002/ijc.25987. Epub 2011 Apr 13. PMID: 21328342.
1: Tazzyman S, Barry ST, Ashton S, Wood P, Blakey D, Lewis CE, Murdoch C. Inhibition of neutrophil infiltration into A549 lung tumors in vitro and in vivo using a CXCR2-specific antagonist is associated with reduced tumor growth. Int J Cancer. 2011 Aug 15;129(4):847-58. doi: 10.1002/ijc.25987. PubMed PMID: 21328342.
2: Seaton A, Maxwell PJ, Hill A, Gallagher R, Pettigrew J, Wilson RH, Waugh DJ. Inhibition of constitutive and cxc-chemokine-induced NF-kappaB activity potentiates ansamycin-based HSP90-inhibitor cytotoxicity in castrate-resistant prostate cancer cells. Br J Cancer. 2009 Nov 3;101(9):1620-9. doi: 10.1038/sj.bjc.6605356. PubMed PMID: 19809428; PubMed Central PMCID: PMC2778515.
3: Wilson C, Maxwell PJ, Longley DB, Wilson RH, Johnston PG, Waugh DJ. Constitutive and treatment-induced CXCL8-signalling selectively modulates the efficacy of anti-metabolite therapeutics in metastatic prostate cancer. PLoS One. 2012;7(5):e36545. doi: 10.1371/journal.pone.0036545. PubMed PMID: 22590561; PubMed Central PMCID: PMC3348872.
4: Wilson C, Wilson T, Johnston PG, Longley DB, Waugh DJ. Interleukin-8 signaling attenuates TRAIL- and chemotherapy-induced apoptosis through transcriptional regulation of c-FLIP in prostate cancer cells. Mol Cancer Ther. 2008 Sep;7(9):2649-61. doi: 10.1158/1535-7163.MCT-08-0148. PubMed PMID: 18790747.
5: Seaton A, Scullin P, Maxwell PJ, Wilson C, Pettigrew J, Gallagher R, O'Sullivan JM, Johnston PG, Waugh DJ. Interleukin-8 signaling promotes androgen-independent proliferation of prostate cancer cells via induction of androgen receptor expression and activation. Carcinogenesis. 2008 Jun;29(6):1148-56. doi: 10.1093/carcin/bgn109. PubMed PMID: 18487223.
6: Wilson C, Purcell C, Seaton A, Oladipo O, Maxwell PJ, O'Sullivan JM, Wilson RH, Johnston PG, Waugh DJ. Chemotherapy-induced CXC-chemokine/CXC-chemokine receptor signaling in metastatic prostate cancer cells confers resistance to oxaliplatin through potentiation of nuclear factor-kappaB transcription and evasion of apoptosis. J Pharmacol Exp Ther. 2008 Dec;327(3):746-59. doi: 10.1124/jpet.108.143826. PubMed PMID: 18780829.
