AZD4635 (Synonyms: HTL-1071, Imaradenant) |
Katalog-Nr.GC19049
One-Click Copy Product Info
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AZD4635 (HTL1071) ist ein potenter, selektiver und oral aktiver Adenosin-A2A-Rezeptor (A2AR)-Antagonist. AZD4635 bindet an humanes A2AR mit einem Ki von 1,7 nM und zeigt eine >30-fache SelektivitÄt gegenÜber anderen Adenosinrezeptoren.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1321514-06-0
Sample solution is provided at 25 µL, 10mM.
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AZD4635 is a potent, selective, and oral adenosine 2A receptor (A2AR) inhibitor, with a Ki value of 1.7nM [1]. AZD4635 can increase the expression of CD25 (IL2Ra), an activation marker on CD8 T cells, and increase the expression of granzyme B on CD4 and CD8 T cells to improve immune activation[2]. AZD4635 has been widely used in different animal models to reduce tumor burden and enhance antitumor immunity [3].
In vitro, AZD4635 treatment at 3µM for 30min significantly reversed the immunosuppressive effect of 5µM 5 '-(N-ethylcarboxamide) adenosine (NECA) on dendritic cells, and increased the expression of ovalbumin (OVA)[4]. After stimulation with anti-CD3 and anti-28 monoclonal antibodies, combined treatment with anti-PD-L1 antibody (10µg/ml) and AZD4635 (0.2 µM) for 6 hours enhanced CD8+ T cell function and increased IL-2 and IFN-γ secretion[5].
In vivo, AZD4635 (25mg/kg) administered by gavage once daily for 15 days in combination with sodium polyoxotungstate (POM-1) and anti-CD73 antibody treatment resulted in enhanced T cell activation in the spleen and increased IFN-γ and monocyte levels in the spleen and bone marrow in a mouse model of myeloma[6].
References:
[1] Borodovsky A, Wang Y, Ye M, et al. Preclinical pharmacodynamics and antitumor activity of AZD4635, a novel adenosine 2A receptor inhibitor that reverses adenosine mediated T cell suppression[J]. Cancer Research, 2017, 77(13_Supplement): 5580-5580.
[2] Budhu S, Mane M, Bah M A, et al. Optimizing breast cancer therapy by inhibiting the adenosine receptor and oxygen consumption[J]. Cancer Research, 2023, 83(7_Supplement): 2517-2517.
[3] Borodovsky A, Wang Y, Ye M, et al. Inhibition of A2AR by AZD4635 induces anti-tumor immunity alone and in combination with anti-PD-L1 in preclinical models[J]. Cancer Research, 2018, 78(13_Supplement): 3751-3751.
[4] Borodovsky A, Barbon C M, Wang Y, et al. Small molecule AZD4635 inhibitor of A2AR signaling rescues immune cell function including CD103+ dendritic cells enhancing anti-tumor immunity[J]. Journal for Immunotherapy of Cancer, 2020, 8(2): e000417.
[5] Li J, Huang H H, Tu B, et al. Reversal of the CD8+ T-Cell exhaustion induced by chronic HIV-1 infection through combined blockade of the adenosine and PD-1 pathways[J]. Frontiers in Immunology, 2021, 12: 687296.
[6] Yang R, Elsaadi S, Misund K, et al. Conversion of ATP to adenosine by CD39 and CD73 in multiple myeloma can be successfully targeted together with adenosine receptor A2A blockade[J]. Journal for immunotherapy of cancer, 2020, 8(1): e000610.
| Cell experiment [1]: | |
Cell lines | Mouse bone marrow-derived progenitor cells |
Preparation Method | Mouse bone marrow-derived precursor cells were cultured for 16 days in complete T cell medium supplemented with 200ng/ml rmFLT3L and 5ng/ml rmGM-CSF. After initial incubation with growth cytokines for 10 days, 3µM AZD4635 or DMSO (as a control) was added, and after 30 minutes of incubation, 5µM NECA was added. After that, the culture with growth cytokines was continued for 6 days before the cells were harvested for analysis. |
Reaction Conditions | 3µM; 30min |
Applications | AZD4635 treatment rescued the immunosuppressive effects of mouse bone marrow-derived progenitor cells and promoted the generation of bone marrow-derived precursors into CD103+ dendritic cell. |
| Animal experiment [2]: | |
Animal models | C57BL/KalwRij mice |
Preparation Method | C57BL/KalwRij mice were raised in a standard sterile environment and injected intravenously with 2×105 5T33 multiple myeloma (MM) cells on day 0 and intraperitoneally with 10mg/kg monoclonal anti-CD73 antibody on days 2, 4, 8, 11, and 15. AZD4635 (25mg/kg) was administered by gavage once a day from day 0, and mice were sacrificed on day 15, and spleen tissues were collected for analysis. |
Dosage form | 25mg/kg/day for 15 days; p.o. |
Applications | AZD4635 treatment resulted in a significant decrease in the number of CD138 MM cells in the spleen of mice, an increase in the number of monocytes, and enhanced T cell activation. |
References: | |
| Cas No. | 1321514-06-0 | SDF | |
| Überlieferungen | HTL-1071, Imaradenant | ||
| Canonical SMILES | NC1=NC(C2=CC=C(F)C=C2)=C(C3=CC(Cl)=NC(C)=C3)N=N1 | ||
| Formula | C15H11ClFN5 | M.Wt | 315.73 |
| Löslichkeit | DMSO : ≥ 83.3 mg/mL (263.83 mM);Water : < 0.1 mg/mL (insoluble) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.1673 mL | 15.8363 mL | 31.6726 mL |
| 5 mM | 633.5 μL | 3.1673 mL | 6.3345 mL |
| 10 mM | 316.7 μL | 1.5836 mL | 3.1673 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 17 reference(s) in Google Scholar.)