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Purity: ≥98%
LSZ-102 is a potent, orally bioactive, selective ERα antagonist that has the potential to treat estrogen receptor positive breast cancer. It also functions as an ERα degrader, with an IC50 of 0.2 nM. About 74% of cases of breast cancer are estrogen receptor alpha (ERα) positive, and in these cases, ERα is the main factor promoting cell division. Aromatase inhibitors, selective estrogen receptor modulators, and selective estrogen receptor destroyers (SERDs) have long been staples in the treatment of ERα positive breast cancer. LSZ102 is a substance that is presently undergoing clinical trials to treat breast cancer that is ERα positive.
| Targets |
estrogen receptor
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| ln Vitro |
LSZ-102 estrogen receptor degrader that is being tested in Phase I/Ib trials for the treatment of ERα positive breast cancer. Its IC50 is 0.2 nM. MCF-7 cells treated with a 10 μM solution of LSZ-102 for 24 hours show significant degradation of ERα. When MCF-7 cells are incubated with LSZ-102 at a half inhibitory concentration of 1.7 nM, a strong inhibition of cell proliferation is seen. Results using charcoal-stripped serum treated with E2 show that LSZ-102 effectively inhibits the estrogen-induced activation of the ERE-luciferase reporter with an IC50 of 0.3 nM[1].
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| ln Vivo |
When mice are administered LSZ-102 once daily at a dose of 20 mg/kg, their tumor growth is significantly inhibited compared to the control group that receives vehicle alone. This leads to tumor stasis (mean change in tumor volume of LSZ-102 vs control=%ΔT/ΔC of 2.4% on day 48, p<0.05). Male Sprague-Dawley rats given a 3 mg/kg solution of LSZ-102 exhibit a dose-normalized exposure of 620 nM•h and 33% bioavailability[1].
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| Enzyme Assay |
Reduction in growth factors In 96-well plates, MCF-7 ERE-luc cells are used and seeded (10 000 cells/well) in CSS medium. Cells are incubated for a full night before being treated with LSZ-102 for 24 hours while being exposed to 0.1 nM estradiol. After that, cells are lysed, and the Bright-Glo assay is used to measure the amount of luciferase activity[1].
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| Animal Protocol |
In tumor xenograft studies, female athymic nude mice are employed. Injecting 200 μL of MCF-7 cells subcutaneously into the right axillary mammary fat pad area of each animal. There are twice-weekly measurements of tumor volume and body weight. Mice are randomly divided into groups once tumors have an average volume of less than 200 mm3. LSZ-102 (20 mg/kg) or tamoxifen (60 mg/kg) given orally to animals five days a week are the three options[1].
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| References | |
| Additional Infomation |
LSZ-102 is under investigation in clinical trial NCT02734615 (Phase I/Ib Trial of LSZ102 Single Agent or LSZ102 + LEE011 or LSZ102 + BYL719 in ER+ Breast Cancers).
Selective Estrogen Receptor Degrader LSZ102 is an selective estrogen receptor (ER) degrader (SERD), with potential antineoplastic activity. Upon administration of LSZ102, this agent binds to the ER and induces the degradation of the receptor. This prevents ER activation and ER-mediated signaling, and inhibits the growth and survival of ER-expressing cancer cells. |
| Molecular Formula |
C25H17F3O4S
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|---|---|---|
| Molecular Weight |
470.460296392441
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| Exact Mass |
470.08
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| Elemental Analysis |
C, 63.83; H, 3.64; F, 12.11; O, 13.60; S, 6.81
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| CAS # |
2135600-76-7
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| Related CAS # |
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| PubChem CID |
118574930
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| Appearance |
White to light yellow solid powder
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| LogP |
6.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
33
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| Complexity |
712
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C1=C(C=CC(=C1)F)C2=C(C3=C(S2)C=C(C=C3)O)OC4=CC=C(C=C4)/C=C/C(=O)O)(F)F
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| InChi Key |
SJXNPGGVGZXKKI-NYYWCZLTSA-N
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| InChi Code |
InChI=1S/C25H17F3O4S/c1-25(27,28)20-12-15(26)5-9-18(20)24-23(19-10-6-16(29)13-21(19)33-24)32-17-7-2-14(3-8-17)4-11-22(30)31/h2-13,29H,1H3,(H,30,31)/b11-4+
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| Chemical Name |
(E)-3-[4-[[2-[2-(1,1-difluoroethyl)-4-fluorophenyl]-6-hydroxy-1-benzothiophen-3-yl]oxy]phenyl]prop-2-enoic acid
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| Synonyms |
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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 (e.g. under nitrogen), avoid exposure to moisture. |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (3.55 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 16.7 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: ≥ 1.67 mg/mL (3.55 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 16.7 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: ≥ 1.67 mg/mL (3.55 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 | 2.1256 mL | 10.6279 mL | 21.2558 mL | |
| 5 mM | 0.4251 mL | 2.1256 mL | 4.2512 mL | |
| 10 mM | 0.2126 mL | 1.0628 mL | 2.1256 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 |
| NCT02734615 | Terminated | Drug: LSZ102 Drug: LEE011 |
Advanced or Metastatic ER+ Breast Cancer |
Novartis Pharmaceuticals | June 14, 2016 | Phase 1 |
 J Med Chem.2018 Apr 12;61(7):2837-2864. |
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