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| Targets |
Taragarestrant meglumine is an orally bioavailable, selective estrogen receptor degrader (SERD). It targets the Estrogen Receptor (ER) by binding to it and inducing its degradation. This leads to a sustained inhibition of ER-dependent gene transcription and cell growth, which is a key therapeutic strategy for ER+ breast cancer research.
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| ln Vitro |
Taragarestrant meglumine shows potent activity in various ER+ breast cancer cell lines, including those with ESR1 mutations. It effectively downregulates ERalpha protein levels and inhibits cell proliferation. It demonstrates a good pharmacokinetic (PK) profile, including antitumor activity in ESR1 mutant models.
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| ln Vivo |
Superior PK profiles make taragarestrant (D-0502) a good candidate for clinical development[1].
In xenograft models of ER+ breast cancer, Taragarestrant meglumine demonstrates significant tumor growth inhibition and regression. It possesses sufficient oral exposure to be tested in vivo and shows robust efficacy, making it a valuable tool for studying ER+ cancer and potential resistance mechanisms. |
| Enzyme Assay |
Cell-free ER binding assays are performed using a time-resolved fluorescence resonance energy transfer (TR-FRET) format. A GST-tagged ER ligand-binding domain (LBD), a terbium-labeled anti-GST antibody, and a fluorescein-labeled coactivator peptide are used. The compound's ability to competitively displace an agonist is measured, and the IC50 is determined by the loss of TR-FRET signal.
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| Cell Assay |
ER+ breast cancer cell lines (e.g., MCF-7, T47D) are seeded in 96-well plates and treated with a dilution series of Taragarestrant meglumine for 5-7 days. Cell viability is measured using the CellTiter-Glo luminescent cell viability assay to calculate the half-maximal inhibitory concentration (IC50) for growth inhibition. ERalpha protein levels are assessed via Western blot to confirm target degradation.
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| Animal Protocol |
The in vivo efficacy of Taragarestrant meglumine is evaluated in a xenograft mouse model. Female athymic nude mice are inoculated subcutaneously with MCF-7 or patient-derived ER+ breast cancer cells. When tumors reach a predetermined size, mice are randomized into treatment groups and the compound is administered via oral gavage (p.o.). Tumor volumes are measured bi-weekly with calipers. Endpoints include tumor growth inhibition (TGI) and analysis of ERalpha levels in excised tumors.
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| ADME/Pharmacokinetics |
Taragarestrant meglumine is characterized by its excellent oral bioavailability and favorable pharmacokinetic profile. It is designed to achieve high and sustained systemic exposure, allowing for continuous ER degradation in vivo. Its PK properties support a once-daily oral dosing regimen, which is essential for maintaining target coverage and driving tumor regression.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies indicate that Taragarestrant meglumine is well-tolerated at therapeutic doses. The primary observed effects are on-target pharmacodynamic effects related to ER degradation. No significant off-target toxicities have been reported in preclinical models, supporting its potential for further development.
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| References | |
| Additional Infomation |
Taragarestrant (D-0502) meglumine is a next-generation oral SERD. It has entered clinical trials (Phase 1/2) for patients with ER+ HER2- advanced or metastatic breast cancer. It is a promising research compound for evaluating the potential of oral SERDs to improve patient outcomes and overcome resistance to current endocrine therapies.
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| Molecular Formula |
C32H42CL2FN3O7
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|---|---|
| Molecular Weight |
670.596190929413
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| Exact Mass |
669.238
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| Elemental Analysis |
C, 57.31; H, 6.31; Cl, 10.57; F, 2.83; N, 6.27; O, 16.70
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| CAS # |
2446618-18-2
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| Related CAS # |
2118899-51-5
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| PubChem CID |
164888953
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| Appearance |
Off-white to yellow solid powder
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| Hydrogen Bond Donor Count |
8
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
45
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| Complexity |
842
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| Defined Atom Stereocenter Count |
6
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| SMILES |
[C@@H](O)([C@@H](O)CNC)[C@H](O)[C@H](O)CO.C(N1[C@@H](CC2C3=CC=CC=C3NC=2[C@H]1C1C(=CC(/C=C/C(=O)O)=CC=1Cl)Cl)C)C(F)(C)C
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| InChi Key |
QLOWUROBGXPIGD-DAIKAQOVSA-N
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| InChi Code |
InChI=1S/C25H25Cl2FN2O2.C7H17NO5/c1-14-10-17-16-6-4-5-7-20(16)29-23(17)24(30(14)13-25(2,3)28)22-18(26)11-15(12-19(22)27)8-9-21(31)32;1-8-2-4(10)6(12)7(13)5(11)3-9/h4-9,11-12,14,24,29H,10,13H2,1-3H3,(H,31,32);4-13H,2-3H2,1H3/b9-8+;/t14-,24-;4-,5+,6+,7+/m10/s1
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| Chemical Name |
(E)-3-[3,5-dichloro-4-[(1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]prop-2-enoic acid;(2R,3R,4R,5S)-6-(methylamino)hexane-1,2,3,4,5-pentol
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| Synonyms |
Taragarestrant meglumine; D0502 meglumine; Taragarestrant (meglumine); 2446618-18-2; D-0502 meglumine; P9XH25HH8P;
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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: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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: 20.83 mg/mL (31.06 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.10 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 (3.10 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 (3.10 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 | 1.4912 mL | 7.4560 mL | 14.9120 mL | |
| 5 mM | 0.2982 mL | 1.4912 mL | 2.9824 mL | |
| 10 mM | 0.1491 mL | 0.7456 mL | 1.4912 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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