| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
A2AR ( Kd = 1.4 nM ); A2bR ( Kd = 2 nM )
Etrumadenant targets the adenosine A2A and A2B receptors. It acts as a dual antagonist, blocking the binding of adenosine to both receptors. Adenosine is a key immunosuppressive metabolite in the tumor microenvironment that suppresses T cell function. By blocking A2A and A2B receptors, etrumadenant relieves adenosine-mediated immunosuppression and enhances the activity of T cells and other immune cells. |
|---|---|
| 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].
In vitro, Etrumadenant has been shown to potently antagonize the adenosine A2A and A2B receptors. It enhances T cell proliferation and cytokine production in the presence of adenosine. The compound also enhances the activity of immune cells, including natural killer cells and dendritic cells. Etrumadenant has been shown to have a favorable selectivity profile over other adenosine receptors. |
| 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].
In vivo, Etrumadenant has been studied in animal models of cancer. The compound has been shown to inhibit tumor growth and to enhance the efficacy of immune checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 antibodies. Etrumadenant is typically administered orally. The compound's antitumor activity is associated with increased immune cell infiltration and activation in the tumor microenvironment. |
| Enzyme Assay |
In vitro receptor binding assays for Etrumadenant typically involve measuring its affinity for the adenosine A2A and A2B receptors using radioligand binding. The compound is incubated with membrane preparations from cells expressing the receptors and a radiolabeled ligand. The concentration of Etrumadenant required to displace 50% of the radioligand (IC50) is determined, and the Ki value is calculated. The selectivity of Etrumadenant for A2A and A2B over A1 and A3 receptors can be assessed.
|
| 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.
In vitro cell-based studies with Etrumadenant typically involve cultured immune cells, such as T cells or peripheral blood mononuclear cells. Cells are treated with Etrumadenant at various concentrations in the presence of adenosine. T cell proliferation is measured by [3H]thymidine incorporation or by CFSE dilution. Cytokine production, such as IFN-γ and IL-2, is measured by ELISA. The effect of Etrumadenant on immune cell function is assessed. |
| 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] In vivo animal studies with Etrumadenant are typically conducted in syngeneic mouse models of cancer. Tumor-bearing mice are treated with Etrumadenant alone or in combination with immune checkpoint inhibitors via oral administration. Tumor growth is measured over time, and tumor growth inhibition is calculated. Tumor tissues are collected for assessment of immune cell infiltration and activation. Pharmacokinetic studies are performed by measuring compound concentrations in plasma and tissues. |
| ADME/Pharmacokinetics |
The pharmacokinetic properties of Etrumadenant have been studied in preclinical and clinical settings. Following oral administration, the compound is absorbed from the gastrointestinal tract. Etrumadenant has a favorable pharmacokinetic profile with good oral bioavailability. Detailed PK parameters such as Cmax, Tmax, AUC, and half-life have been reported in the literature.
|
| Toxicity/Toxicokinetics |
The toxicity profile of Etrumadenant has been evaluated in preclinical and clinical studies. The compound has been shown to have a favorable safety profile in clinical trials. The most common adverse effects are mild and include headache, fatigue, and gastrointestinal upset. Etrumadenant is generally well-tolerated at therapeutic doses.
|
| References |
|
| Additional Infomation |
Etrumadenant is an orally bioavailable antagonist of adenosine A2A receptor (A2AR; ADORA2A) and A2B receptor (A2BR; ADORA2B) molecule immune regulatory checkpoint molecules, possessing potential immunomodulatory and antitumor activities. After administration, edrusadanan competitively binds to A2AR and A2BR expressed on various tumor-bearing immune cells, such as dendritic cells (DCs), natural killer (NK) cells, macrophages, and T lymphocytes, against tumor-released adenosine. The binding of edrusadanan to A2AR and A2BR inhibits A2AR/A2BR activity, thereby blocking adenosine-A2AR/A2BR-mediated signal transduction. A2AR/A2BR inhibitors can activate and enhance the proliferation of various immune cells, eliminate adenosine-mediated immunosuppression in the tumor microenvironment (TME), and activate the immune system to produce an antitumor immune response against cancer cells, ultimately leading to tumor cell death. A2AR and A2BR are G protein-coupled signaling receptors expressed on the cell surface of various immune cells. Tumor cells often overproduce adenosine, which plays a key role in immunosuppression and tumor cell proliferation.
Etrumadenant (AB928) is a dual antagonist of adenosine A2A and A2B receptors being developed for the treatment of cancer. It is designed to enhance anti-tumor immune responses by blocking the immunosuppressive effects of adenosine in the tumor microenvironment. Etrumadenant is being investigated in clinical trials in combination with immune checkpoint inhibitors and other cancer therapies. The compound is not yet FDA-approved. |
| Molecular Formula |
C23H22N8O
|
|---|---|
| Molecular Weight |
426.473783016205
|
| Exact Mass |
426.19
|
| Elemental Analysis |
C, 64.77; H, 5.20; N, 26.27; O, 3.75
|
| CAS # |
2239273-34-6
|
| Related CAS # |
2239273-34-6
|
| PubChem CID |
135242184
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
1.4
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
32
|
| Complexity |
680
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
BUXIAWLTBSXYSW-UHFFFAOYSA-N
|
| 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)
|
| Chemical Name |
3-[2-amino-6-[1-[[6-(2-hydroxypropan-2-yl)pyridin-2-yl]methyl]triazol-4-yl]pyrimidin-4-yl]-2-methylbenzonitrile
|
| 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
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 85~250 mg/mL (199.3~586.2 mM)
Ethanol: ~5 mg/mL |
|---|---|
| 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 |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA