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Purity: ≥98%
Etrumadenant (AB928; AB-928) is a first-in-class, clinical stage, oral and dual antagonist of the A2aR and A2bR adenosine receptors with potential anticancer and immunomodulatory activity. In conjunction with chemotherapy, it can inhibit adenosine-mediated immunosuppression, resulting in increased immune activation and decreased tumor growth.
| Targets |
A2AR ( Kd = 1.4 nM ); A2bR ( Kd = 2 nM )
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|---|---|
| ln Vitro |
MoDC that underwent adenosine differentiation in human in vitro cell cultures demonstrated a reduced capacity to induce IFN-γ secretion from allogenic CD4+ T-cells in a MLR. Etrumadenant is added, and this suppression is greatly reversed. A cassette of 39 genes that are controlled by adenosine during moDC differentiation was discovered by multiplexed gene expression profiling with NanoString. These changes in gene expression are rescued by etrumadenant[2].
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| ln Vivo |
Etrumadenant plus chemotherapy leads to a markedly decreased tumor volume in vivo when AT3-OVA tumors are used for treatment; Etrumadenant plus NSC 266046 produces similar outcomes. Moreover, AB928 can inhibit the growth of B16-F10 tumors when used alone or in conjunction with α-PD-1 therapy. In mouse syngeneic tumors, etrumadenant stimulates the antitumor immune response, which inhibits tumor growth and increases immune cell infiltration[2].
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| Cell Assay |
PBMC is used to isolate CD4+ or CD8+ T cells using RosetteSep separation. Adenosine/EHNA +/- AB928 +/- CD2/CD3/CD28 microbeads are then used to stimulate the cells. After six days in IL-4/GM-CSF +/- adenosine/EHNA, +/- AB928; human CD14+ cells are differentiated into moDC. When moDCs are activated by LPS or IFN-y, adenosine is present. Before initiating the mixed leukocyte reaction (MLR), cells are rinsed in excess buffer to get rid of any remaining adenosine. Four days after the moDC/CD4 co-culture is started, supernatants are extracted.
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| Animal Protocol |
female C57BL/6 mice
100 mg/kg Oral gavage Mouse syngeneic tumor studies were conducted using C57BL/6 mice inoculated with mouse mammary tumor AT3-OVA or melanoma B16-F10 cells. Tumors were subsequently treated with doxorubicin, oxaliplatin, or α-PD-1 +/- AB928.[2] |
| References |
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| Additional Infomation |
Etrumadenant is an orally bioavailable antagonist of both the immunomodulatory checkpoint molecules adenosine A2A receptor (A2AR; ADORA2A) and A2B receptor (A2BR; ADORA2B), with potential immunomodulating and antineoplastic activities. Upon administration, etrumadenant competes with tumor-released adenosine for binding to A2AR and A2BR expressed on numerous intra-tumoral immune cells, such as dendritic cells (DCs), natural killer (NK) cells, macrophages and T-lymphocytes. The binding of AB928 to A2AR and A2BR inhibits A2AR/A2BR activity and prevents adenosine-A2AR/A2BR-mediated signaling. A2AR/A2BR inhibition activates and enhances the proliferation of various immune cells, abrogates the adenosine-mediated immunosuppression in the tumor microenvironment (TME) and activates the immune system to exert anti-tumor immune responses against cancer cells, which leads to tumor cell killing. A2AR and A2BR, G protein-coupled signaling receptors, are expressed on the cell surfaces of numerous immune cells. Adenosine is often overproduced by tumor cells and plays a key role in immunosuppression and tumor cell proliferation.
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| Molecular Formula |
C23H22N8O
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|---|---|
| Molecular Weight |
426.473783016205
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| Exact Mass |
426.19
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| Elemental Analysis |
C, 64.77; H, 5.20; N, 26.27; O, 3.75
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| CAS # |
2239273-34-6
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| Related CAS # |
2239273-34-6
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| PubChem CID |
135242184
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
1.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
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| Complexity |
680
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
BUXIAWLTBSXYSW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H22N8O/c1-14-15(11-24)6-4-8-17(14)18-10-19(28-22(25)27-18)20-13-31(30-29-20)12-16-7-5-9-21(26-16)23(2,3)32/h4-10,13,32H,12H2,1-3H3,(H2,25,27,28)
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| Chemical Name |
3-[2-amino-6-[1-[[6-(2-hydroxypropan-2-yl)pyridin-2-yl]methyl]triazol-4-yl]pyrimidin-4-yl]-2-methylbenzonitrile
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| Synonyms |
AB-928; Etrumadenant; AB928; AB928; 2239273-34-6; Etrumadenant; AB-928; 3-(2-Amino-6-(1-((6-(2-hydroxypropan-2-yl)pyridin-2-yl)methyl)-1H-1,2,3-triazol-4-yl)pyrimidin-4-yl)-2-methylbenzonitrile; 3-[2-Amino-6-[1-[[6-(2-hydroxypropan-2-yl)pyridin-2-yl]methyl]triazol-4-yl]pyrimidin-4-yl]-2-methylbenzonitrile; Etrumadenant [USAN]; W0ZE0NT8IF;AB 928
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 85~250 mg/mL (199.3~586.2 mM)
Ethanol: ~5 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.88 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.88 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.88 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 5% DMSO + 95% Corn oil: 0.7mg/ml (1.64mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3448 mL | 11.7242 mL | 23.4483 mL | |
| 5 mM | 0.4690 mL | 2.3448 mL | 4.6897 mL | |
| 10 mM | 0.2345 mL | 1.1724 mL | 2.3448 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04660812 | Active Recruiting |
Drug: Etrumadenant Drug: AB680 |
Metastatic Colorectal Cancer | Arcus Biosciences, Inc. | May 10, 2021 | Phase 1 Phase 2 |
| NCT04262856 | Active Recruiting |
Drug: Domvanalimab Drug: Etrumadenant |
Lung Cancer Non Small Cell Lung Cancer |
Arcus Biosciences, Inc. | May 28, 2020 | Phase 2 |
| NCT03846310 | Active Recruiting |
Drug: Etrumadenant Drug: Zimberelimab Drug: Carboplatin Drug: Pemetrexed |
Non Small Cell Lung Cancer Nonsquamous Nonsmall Cell Neoplasm of Lung |
Arcus Biosciences, Inc. | April 1, 2019 | Phase 1 |
| NCT04381832 | Active Recruiting |
Drug: Etrumadenant Drug: Zimberelimab |
Prostatic Neoplasms, Castration -Resistant Prostatic Cancer, Castration -Resistant |
Arcus Biosciences, Inc. | July 7, 2020 | Phase 1 Phase 2 |
| NCT05335941 | Recruiting | Drug: Etrumadenant Drug: Zimberelimab |
Urothelial Carcinoma Metastatic Cancer |
M.D. Anderson Cancer Center | June 13, 2023 | Phase 2 |
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