| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
| Targets |
This compound is a potent agonist of the glucocorticoid receptor (GR), a member of the nuclear receptor superfamily. Upon binding to GR, the glucocorticoid payload translocates to the nucleus, where it modulates the transcription of anti‑inflammatory and immunosuppressive target genes. The Ala‑Ala‑Mal linker is designed for conjugation to antibodies, enabling targeted delivery to specific cell types (e.g., inflammatory immune cells).
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|---|---|
| ln Vitro |
In vitro, the glucocorticoid receptor agonist-1 Ala‑Ala‑Mal moiety retains high potency at the GR (exact EC50 not published but inferred from similar glucocorticosteroids). Following conjugation to a targeting antibody (e.g., adalimumab, an anti‑TNFalpha antibody) via the maleimide group, the resulting ADC is expected to exhibit potent, target‑dependent suppression of pro‑inflammatory cytokine production (e.g., TNFalpha, IL‑6, IL‑1beta) in activated immune cells.
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| ln Vivo |
In vivo activity data for this specific conjugate have not been published. Based on the known pharmacology of glucocorticoids and ADC technology, an ADC prepared with this compound conjugated to a targeting antibody (e.g., adalimumab) would be expected to deliver the glucocorticoid payload selectively to inflamed tissues or activated immune cells, reducing systemic glucocorticoid exposure and associated side effects (e.g., hyperglycemia, osteoporosis, immunosuppression).
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| Enzyme Assay |
Non‑cell‑based binding is assessed by fluorescence polarization (FP) or time‑resolved FRET (TR‑FRET) using purified recombinant glucocorticoid receptor ligand‑binding domain (GR‑LBD). Increasing concentrations of the compound (0.001-100 microM) are incubated with GR‑LBD and a fluorescently labeled glucocorticoid tracer (e.g., FITC‑dexamethasone). The IC50 or EC50 for displacement/binding is calculated.
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| Cell Assay |
For GR agonist activity, HEK‑293 cells stably transfected with a glucocorticoid response element (GRE)‑luciferase reporter are treated with serial dilutions of the compound (0.001-10 microM) for 24 h. Luciferase activity is measured, and EC50 values are calculated. For ADC activity, antigen‑positive cells (e.g., TNFalpha‑producing THP‑1 macrophages for an anti‑TNFalpha ADC) are treated with the complete ADC (0.001-100 nM) and cytokine production (TNFalpha, IL‑6) is measured by ELISA after LPS stimulation.
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| Animal Protocol |
For in vivo evaluation of an ADC built with this payload‑linker, immunocompromised mice engrafted with antigen‑positive human cells (or a mouse model of inflammatory disease) would be used. The ADC is administered intravenously at 1-10 mg/kg once weekly for 2-4 weeks. Efficacy endpoints include suppression of pro‑inflammatory cytokines in plasma, reduction of immune cell infiltration into inflamed tissues (e.g., joint sections in arthritis models), and improvement in disease activity scores.
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| ADME/Pharmacokinetics |
Pharmacokinetic data specifically for this compound have not been published. When conjugated to an antibody, the ADC would exhibit antibody‑like PK: low clearance (0.2-0.5 mL/h/kg), long half‑life (5-10 days), and minimal release of free payload in circulation. The maleimide linkage ensures stable conjugation, while the Ala‑Ala spacer may be cleaved by lysosomal proteases after ADC internalization.
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| Toxicity/Toxicokinetics |
As a glucocorticoid receptor agonist, the payload component of this conjugate carries the risk of systemic glucocorticoid side effects (e.g., hyperglycemia, osteoporosis, adrenal suppression) if prematurely released from the ADC. The conjugate is designed to minimize such effects through targeted delivery. No standalone toxicity studies for this specific compound have been published, and it is not an approved drug.
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| References | |
| Additional Infomation |
Glucocorticoid receptor agonist-1 Ala‑Ala‑Mal is a research‑grade chemical for the construction of steroid‑based ADCs. It has not been approved for therapeutic use and has not entered clinical trials. Its value lies in exploring the potential of targeted glucocorticoid therapy, which could reduce the systemic toxicities associated with long‑term glucocorticoid treatment in chronic inflammatory and autoimmune diseases. Conjugation to adalimumab (anti‑TNFalpha) or other targeting antibodies is of particular interest.
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| Molecular Formula |
C48H54N4O11
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|---|---|
| Molecular Weight |
862.96257352829
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| Exact Mass |
862.378
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| CAS # |
2166376-51-6
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| PubChem CID |
134491695
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| Appearance |
White to light yellow solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
63
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| Complexity |
1960
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| Defined Atom Stereocenter Count |
11
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| SMILES |
O1[C@H](C2C=CC(CC3C=CC=C(C=3)NC([C@H](C)NC([C@H](C)NC(CCN3C(C=CC3=O)=O)=O)=O)=O)=CC=2)O[C@@H]2C[C@H]3[C@@H]4CCC5=CC(C=C[C@]5(C)[C@H]4[C@H](C[C@]3(C)[C@]12C(CO)=O)O)=O
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| InChi Key |
STCNTKNIXVQMDF-ZYKKSPNHSA-N
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| InChi Code |
InChI=1S/C48H54N4O11/c1-26(49-39(57)17-19-52-40(58)14-15-41(52)59)43(60)50-27(2)44(61)51-32-7-5-6-29(21-32)20-28-8-10-30(11-9-28)45-62-38-23-35-34-13-12-31-22-33(54)16-18-46(31,3)42(34)36(55)24-47(35,4)48(38,63-45)37(56)25-53/h5-11,14-16,18,21-22,26-27,34-36,38,42,45,53,55H,12-13,17,19-20,23-25H2,1-4H3,(H,49,57)(H,50,60)(H,51,61)/t26-,27-,34-,35-,36-,38+,42+,45+,46-,47-,48+/m0/s1
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| Chemical Name |
(2S)-2-[3-(2,5-dioxopyrrol-1-yl)propanoylamino]-N-[(2S)-1-[3-[[4-[(1S,2S,4R,6R,8S,9S,11S,12S,13R)-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-16-oxo-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-6-yl]phenyl]methyl]anilino]-1-oxopropan-2-yl]propanamide
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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 : 110 mg/mL (127.47 mM)
H2O : < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (3.19 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 27.5 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: 2.75 mg/mL (3.19 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 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: ≥ 2.75 mg/mL (3.19 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 | 1.1588 mL | 5.7940 mL | 11.5880 mL | |
| 5 mM | 0.2318 mL | 1.1588 mL | 2.3176 mL | |
| 10 mM | 0.1159 mL | 0.5794 mL | 1.1588 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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