| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
The primary target of this compound is the Glucocorticoid Receptor (GR), a nuclear receptor that regulates inflammation and immune responses. As a potent agonist, it activates GR-mediated signaling pathways, which is a key strategy for developing anti-inflammatory therapies and ADCs.
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| ln Vitro |
Glucocorticoid receptor agonist-2's half-life constants (IC50) for binding to progesterone receptors (PR) and glucocorticoid receptors (GR) are 7.3 and 6.6 nM, respectively[1]. For the glucocorticoid response element (GRE) reporter gene and the mineralocorticoid receptor (MR), the EC50 values of glucocorticoid receptor agonist-2 are 0.2 and 442 nM, respectively [1]. On the mineralocorticoid receptor, the agonist activity of glucocorticoid receptor agonist-2 has an EC50 value of 149 nM[1].
The compound exhibits potent GR agonist activity in cell-free biochemical assays, with an IC50 of 6.6 nM.As the active warhead for ADCs, it is conjugated to antibodies to deliver a highly potent anti-inflammatory payload directly to target cells, where it is internalized and released to activate the GR. |
| ln Vivo |
In vivo studies for this compound are expected to leverage its activity as part of ADCs. While data for the parent payload are unavailable, the corresponding ADC (ABBV-3373) has demonstrated the ability to effectively deliver this GR agonist to sites of inflammation, achieving therapeutic efficacy while minimizing systemic side effects.
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| Enzyme Assay |
Cell-free binding affinity is determined using a standard radioligand binding assay. The glucocorticoid receptor is incubated with a radiolabeled high-affinity ligand (such as 3H-dexamethasone) and varying concentrations of the test compound. After incubation, the bound and free radioligands are separated, and the half-maximal inhibitory concentration (IC50) is measured via scintillation counting.
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| Cell Assay |
Cell-based assays for the compound involve its incorporation as a payload in ADCs. The potency of the ADC is evaluated using antigen-expressing cell lines. Cells are treated with the ADC, and cell viability or GR-mediated transcriptional activity is measured. The IC50 of the payload alone (Glucocorticoid receptor agonist-2) is also determined in relevant cell types to confirm its intrinsic activity.
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| Animal Protocol |
In vivo animal model data is not available for this specific compound. The compound is used as a standard in the discovery and validation of ADCs. In vivo studies for such conjugates are typically conducted in rodent models of autoimmune diseases, such as collagen-induced arthritis (CIA) or experimental autoimmune encephalomyelitis (EAE).
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties are not documented for this standalone payload. When conjugated in an ADC, the PK profile is generally determined by the antibody component, which results in a prolonged circulation half-life and targeted delivery, while the conjugated payload remains inactive until released within target cells.
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| Toxicity/Toxicokinetics |
Toxicological and safety profiles for the free payload are not established. As a potent GR agonist, systemic exposure could lead to typical glucocorticoid-related side effects, such as immunosuppression and metabolic disturbances. However, when delivered as an ADC, these toxicities are minimized by targeted delivery to the site of action.
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| References | |
| Additional Infomation |
Glucocorticoid receptor agonist-2 serves as an active reference for ABBV-3373, a research-stage ADC. The development of ADCs with this GR agonist provides a novel strategy to deliver potent anti-inflammatory drugs directly to sites of inflammation, potentially overcoming the systemic side effects associated with conventional glucocorticoid therapies.
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| Molecular Formula |
C34H35F2NO7
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|---|---|
| Molecular Weight |
607.641017198563
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| Exact Mass |
607.238
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| CAS # |
2166378-92-1
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| PubChem CID |
134491916
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| Appearance |
White to off-white solid powder
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
44
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| Complexity |
1250
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| Defined Atom Stereocenter Count |
10
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| SMILES |
F[C@@]12[C@]3(C=CC(C=C3[C@H](C[C@H]1[C@@H]1C[C@@H]3[C@](C(CO)=O)([C@@]1(C)C[C@@H]2O)O[C@H](C1C=CC(=CC=1)OC1C=CC=C(C=1)N)O3)F)=O)C
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| InChi Key |
LCDCPIOGHJGDBP-APTODLHGSA-N
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| InChi Code |
InChI=1S/C34H35F2NO7/c1-31-11-10-20(39)13-25(31)26(35)14-24-23-15-29-34(28(41)17-38,32(23,2)16-27(40)33(24,31)36)44-30(43-29)18-6-8-21(9-7-18)42-22-5-3-4-19(37)12-22/h3-13,23-24,26-27,29-30,38,40H,14-17,37H2,1-2H3/t23-,24-,26-,27-,29+,30+,31-,32-,33-,34+/m0/s1
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| Chemical Name |
(1S,2S,4R,6R,8S,9S,11S,12R,13S,19S)-6-[4-(3-aminophenoxy)phenyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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: 12.5 mg/mL (20.57 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6457 mL | 8.2286 mL | 16.4571 mL | |
| 5 mM | 0.3291 mL | 1.6457 mL | 3.2914 mL | |
| 10 mM | 0.1646 mL | 0.8229 mL | 1.6457 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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