WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206930
CAS#: 1321514-06-0
Description: AZD-4635, also known as HTL-1071, is an orally available, small molecule adenosine A2A receptor antagonist.
MedKoo Cat#: 206930
Name: AZD4635
CAS#: 1321514-06-0
Chemical Formula: C15H11ClFN5
Exact Mass: 315.068
Molecular Weight: 315.7364
Elemental Analysis: C, 57.06; H, 3.51; Cl, 11.23; F, 6.02; N, 22.18
Synonym: imaradenant; AZD-4635; AZD 4635; AZD4635; HTL-1071; HTL 1071; HTL1071.
IUPAC/Chemical Name: 6-(2-chloro-6-methylpyridin-4-yl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine
InChi Key: NCWQLHHDGDXIJN-UHFFFAOYSA-N
InChi Code: InChI=1S/C15H11ClFN5/c1-8-6-10(7-12(16)19-8)14-13(20-15(18)22-21-14)9-2-4-11(17)5-3-9/h2-7H,1H3,(H2,18,20,22)
SMILES Code: NC1=NC(C2=CC=C(F)C=C2)=C(C3=CC(C)=NC(Cl)=C3)N=N1
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
| Biological target: | AZD4635 binds to human A2AR with a Ki of 1.7 nM and shows >30-fold selectivity over other adenosine receptors. In the presence of 0.1, 1 and 10 μM adenosine, the IC50s of AZD4635 for inhibition of cAMP production are 0.79, 10.0 and 142.9 nM, respectively. |
| In vitro activity: | The A2A receptor is a member of the G-coupled receptor family with activation leading to increased intracellular levels of cAMP. The potency of AZD4635 in inhibiting A2AR signaling was determined in a cAMP accumulation assay using CHO cells stably transfected with human A2AR (figure 1D) and stimulated with adenosine (100, 10, 1 and 0.1 µM). Owing to the competitive binding mechanism of inhibition, the antagonist activity (IC50) of AZD4635 was impacted by the adenosine concentration. As the concentration of adenosine was increased, the potency of AZD4635 antagonist activity was reduced, with a linear relationship. AZD4635 demonstrated an IC50 of 0.000794, 0.0123, 0.155 and 2.69 µM at concentrations of 0.1, 1, 10 and 100 µM adenosine. Reference: J Immunother Cancer. 2020 Jul;8(2):e000417. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394305/ |
| In vivo activity: | AZD4635 is an oral antagonist of the high-affinity A2A receptor, which reversed T-cell suppression ex vivo when incubated with the adenosine analog 5′-N-ethylcarboxamidoadenosine. In addition, AZD4635 partially restored CADO-mediated inhibition of T-cell proliferation (figure 4E, online supplementary figure S3C). Reference: J Immunother Cancer. 2020 May;8(1):e000610. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239696/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 56.65 | 179.42 | |
| DMSO:PBS(pH 7.2) (1:3) | 0.25 | 0.79 | |
| DMF | 30.0 | 95.01 |
The following data is based on the product molecular weight 315.7364 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. Borodovsky A, Barbon CM, Wang Y, Ye M, Prickett L, Chandra D, Shaw J, Deng N, Sachsenmeier K, Clarke JD, Linghu B, Brown GA, Brown J, Congreve M, Cheng RK, Dore AS, Hurrell E, Shao W, Woessner R, Reimer C, Drew L, Fawell S, Schuller AG, Mele DA. Small molecule AZD4635 inhibitor of A2AR signaling rescues immune cell function including CD103+ dendritic cells enhancing anti-tumor immunity. J Immunother Cancer. 2020 Jul;8(2):e000417. doi: 10.1136/jitc-2019-000417. PMID: 32727810; PMCID: PMC7394305. 2. Yang R, Elsaadi S, Misund K, Abdollahi P, Vandsemb EN, Moen SH, Kusnierczyk A, Slupphaug G, Standal T, Waage A, Slørdahl TS, Rø TB, Rustad E, Sundan A, Hay C, Cooper Z, Schuller AG, Woessner R, Borodovsky A, Menu E, Børset M, Sponaas AM. Conversion of ATP to adenosine by CD39 and CD73 in multiple myeloma can be successfully targeted together with adenosine receptor A2A blockade. J Immunother Cancer. 2020 May;8(1):e000610. doi: 10.1136/jitc-2020-000610. PMID: 32409420; PMCID: PMC7239696. |
| In vitro protocol: | 1. Borodovsky A, Barbon CM, Wang Y, Ye M, Prickett L, Chandra D, Shaw J, Deng N, Sachsenmeier K, Clarke JD, Linghu B, Brown GA, Brown J, Congreve M, Cheng RK, Dore AS, Hurrell E, Shao W, Woessner R, Reimer C, Drew L, Fawell S, Schuller AG, Mele DA. Small molecule AZD4635 inhibitor of A2AR signaling rescues immune cell function including CD103+ dendritic cells enhancing anti-tumor immunity. J Immunother Cancer. 2020 Jul;8(2):e000417. doi: 10.1136/jitc-2019-000417. PMID: 32727810; PMCID: PMC7394305. |
| In vivo protocol: | 1. Yang R, Elsaadi S, Misund K, Abdollahi P, Vandsemb EN, Moen SH, Kusnierczyk A, Slupphaug G, Standal T, Waage A, Slørdahl TS, Rø TB, Rustad E, Sundan A, Hay C, Cooper Z, Schuller AG, Woessner R, Borodovsky A, Menu E, Børset M, Sponaas AM. Conversion of ATP to adenosine by CD39 and CD73 in multiple myeloma can be successfully targeted together with adenosine receptor A2A blockade. J Immunother Cancer. 2020 May;8(1):e000610. doi: 10.1136/jitc-2020-000610. PMID: 32409420; PMCID: PMC7239696. |
1: Jazayeri A, Andrews SP, Marshall FH. Structurally Enabled Discovery of
Adenosine A(2A) Receptor Antagonists. Chem Rev. 2017 Jan 11;117(1):21-37. doi:
10.1021/acs.chemrev.6b00119. Epub 2016 Jun 22. Review. PubMed PMID: 27333206.
2. http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9236
