| Size | Price | |
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| 100mg | ||
| 250mg | ||
| Other Sizes |
Inupadenant (EOS-850; EOS-100850) is an antagonist of adenosine A2a receptor (A2AR) with anticancer activity. A2AR is a key driver of immunosuppressive tumor microenvironment.
| Targets |
A2A receptor
|
|---|---|
| ln Vitro |
Inupadenant is an orally bioavailable immune checkpoint inhibitor and antagonist of the adenosine A2A receptor (A2AR; ADORA2A), with potential immunomodulating and antineoplastic activities. Upon administration, inupadenant selectively binds to and inhibits A2AR expressed on T-lymphocytes. This prevents tumor-released adenosine from interacting with the A2A receptors, thereby blocking the adenosine/A2AR-mediated inhibition of T-lymphocytes. This results in the proliferation and activation of T-lymphocytes, and stimulates a T-cell-mediated immune response against tumor cells. A2AR, a G protein-coupled receptor, is highly expressed on the cell surfaces of T-cells and, upon activation by adenosine, inhibits their proliferation and activation. Adenosine is often overproduced by cancer cells and plays a key role in immunosuppression.[1]
|
| ln Vivo |
Overall, 42 patients (21 patients in the dose escalation and an additional 21 patients in a monotherapy expansion) with a median of 3 prior regimens were treated as of the data cut off (DCO, 30Nov20).The dose levels investigated, along with the most frequent (>20%) treatment-emergent adverse events (TEAEs) across all dose levels are presented in the table. 7 AEs led to discontinuation; 2 (atrial fibrillation and myocardial infarction) were considered possibly study drug-related by the investigator. No dose reductions were required. Two partial responses (PRs) were reported: melanoma (NRAS-mutant; received prior immunotherapy), and prostate cancer (received antiandrogen and chemotherapy). At the DCO, both PRs were ongoing with a duration of response >230 days. 12 patients had stable disease (SD) as best response and SD >6 months was observed in 3 patients. Response and stable disease were associated with a higher number of cells expressing the A2A receptor within the tumor at baseline, as measured by IHC. Conclusions: Inupadenant monotherapy was generally well-tolerated as of the DCO at a dose of 80 mg twice daily with initial evidence of clinical benefit, including 2 durable PRs in patients who have exhausted standard treatment options. Analysis of pre-treatment tumor biopsies has identified the A2A receptor as a biomarker which may be associated with clinical benefit. Clinical trial information: NCT03873883.
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| Animal Protocol |
This is the phase I portion of an ongoing first-in-human, clinical trial (NCT02740985) to evaluate safety/tolerability, pharmacokinetic, pharmacodynamic and anti-tumor activity of inupadenant in adult patients with solid tumors who have exhausted standard treatment options. In addition, tumor biomarkers, including adenosine-pathway markers by immunohistochemistry (IHC), are being evaluated. We present updated results of the dose escalation, new results from the monotherapy expansion and new analysis of tumor biomarkers.[1]
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| References | |
| Additional Infomation |
Inupadenant is an orally bioavailable immune checkpoint inhibitor and antagonist of the adenosine A2A receptor (A2AR; ADORA2A), with potential immunomodulating and antineoplastic activities. Upon administration, inupadenant selectively binds to and inhibits A2AR expressed on T-lymphocytes. This prevents tumor-released adenosine from interacting with the A2A receptors, thereby blocking the adenosine/A2AR-mediated inhibition of T-lymphocytes. This results in the proliferation and activation of T-lymphocytes, and stimulates a T-cell-mediated immune response against tumor cells. A2AR, a G protein-coupled receptor, is highly expressed on the cell surfaces of T-cells and, upon activation by adenosine, inhibits their proliferation and activation. Adenosine is often overproduced by cancer cells and plays a key role in immunosuppression.
|
| Molecular Formula |
C25H26F2N8O4S2
|
|---|---|
| Molecular Weight |
604.651948451996
|
| Exact Mass |
604.148
|
| Elemental Analysis |
C, 49.66; H, 4.33; F, 6.28; N, 18.53; O, 10.58; S, 10.60
|
| CAS # |
2246607-08-7
|
| Related CAS # |
Inupadenant hydrochloride;2411004-22-1; 2246607-08-7; 2413448-96-9 (esylate)
|
| PubChem CID |
135346794
|
| Appearance |
White to yellow solid powder
|
| LogP |
1.7
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
14
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
41
|
| Complexity |
955
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C[S@](=O)CCOC1=C(C=C(C(=C1)N2CCN(CC2)CCN3C4=C(C5=NC(=NN5C(=N4)N)C6=CC=CO6)SC3=O)F)F
|
| InChi Key |
QYCCLUSYHJXDEX-RWYGWLOXSA-N
|
| InChi Code |
InChI=1S/C25H26F2N8O4S2/c1-41(37)12-11-39-19-14-17(15(26)13-16(19)27)33-7-4-32(5-8-33)6-9-34-22-20(40-25(34)36)23-29-21(18-3-2-10-38-18)31-35(23)24(28)30-22/h2-3,10,13-14H,4-9,11-12H2,1H3,(H2,28,30)/t41-/m0/s1
|
| Chemical Name |
(+)-5-amino-3-{2-[4-(2,4-difluoro-5-{2-[(S)-methanesulfinyl]ethoxy}phenyl)piperazin-1-yl]ethyl}-8-(furan-2-yl)[1,3]thiazolo[5,4-e][1,2,4]triazolo[1,5-c]pyrimidin-2(3H)-one
|
| Synonyms |
Inupadenant; EOS 100850; EOS-850; Inupadenant; 2246607-08-7; Inupadenant [INN]; Inupadenant [USAN]; EOS100850; HQ700V0X06; EOS-100850; INUPADENANT [WHO-DD]; EOS100850; EOS 850; EOS-100850; EOS850
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~41.35 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: ≥ 2.22 mg/mL (3.67 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 22.2 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. View More
Solubility in Formulation 3: ≥ 2.22 mg/mL (3.67 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. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6538 mL | 8.2692 mL | 16.5385 mL | |
| 5 mM | 0.3308 mL | 1.6538 mL | 3.3077 mL | |
| 10 mM | 0.1654 mL | 0.8269 mL | 1.6538 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.
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