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Purity: ≥98%
Abequolixron HCl (formerly RGX-104; SB-742881; SB742881), the hydrochloride salt of RGX104, is a novel potent and orally bioavailable liver-X nuclear hormone receptor-beta (LXR) agonist that modulates innate immunity via transcriptional activation of the ApoE gene. It has potential immunomodulating and antineoplastic activities. RGX-104 selectively targets and binds to LXRbeta, thereby activating LXRbeta-mediated signaling, leading to the transcription of certain tumor suppressor genes and the downregulation of certain tumor promoter genes. This particularly activates the expression of apolipoprotein E (ApoE), a tumor suppressor protein, in tumor cells and certain immune cells. This activates the innate immune system, resulting in depletion of immunosuppressive myeloid-derived suppressor cells (MDSCs), tumor cells and endothelial cells in the tumor microenvironment. This reverses immune evasion, enhances anti-tumor immune responses and inhibits proliferation of tumor cells.
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| ln Vitro |
Cancer immunotherapy is restricted to immune resistance caused by immunosuppressive tumor microenvironment. Pyroptosis involved in antitumor immunotherapy as a new schedule is prospective to reverse immunosuppression. Herein, acidic tumor microenvironment (TME)-evoked MRC nanoparticles (MRC NPs) co-delivering immune agonist RGX-104 and photosensitizer chlorine e6 (Ce6) are reported for pyroptosis-mediated immunotherapy. RGX-104 remodels TME by transcriptional activation of ApoE to regress myeloid-derived suppressor cells' (MDSCs) activity, which neatly creates foreshadowing for intensifying pyroptosis. Considering Ce6-triggered photodynamic therapy (PDT) can strengthen oxidative stress and organelles destruction to increase immunogenicity, immunomodulatory-photodynamic MRC nanodrugs will implement an aforementioned two-pronged strategy to enhance gasdermin E (GSDME)-dependent pyroptosis. RNA-seq analysis of MRC at the cellular level is introduced to first elucidate the intimate relationship between RGX-104 acting on LXR/ApoE axis and pyroptosis, where RGX-104 provides the prerequisite for pyroptosis participating in antitumor therapy. Briefly, MRC with favorable biocompatibility tackles the obstacle of hydrophobic drugs delivery, and becomes a powerful pyroptosis inducer to reinforce immune efficacy. MRC-elicited pyroptosis in combination with anti-PD-1 blockade therapy boosts immune response in solid tumors, successfully arresting invasive metastasis and extending survival based on remarkable antitumor immunity. MRC may initiate a new window for immuno-photo pyroptosis stimulators augmenting pyroptosis-based immunotherapy.[2] Adv Healthc Mater . 2022 Nov;11(21):e2201233.
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| ln Vivo |
When mice with visible tumors are given GW3965 or RGX-104 hydrochloride orally, the growth of many cancer types is considerably suppressed. Large tumor-bearing animals also exhibit strong inhibition of tumor growth. Sometimes the therapy results in either full or partial tumor regression. A broad range of cancers, including as lung cancer, melanoma, glioblastoma, ovarian, renal cell, triple-negative breast, and colon cancer, have responses[1].
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| Additional Infomation |
To the best of our knowledge, RGX-104 represents the first MDSC-targeting therapeutic that sufficiently curbs immune-suppression as a single-agent to elicit CTL activation in humans. These findings suggest that LXR activation may be effective at preventing metastasis formation and inhibiting progression of metastatic disease given its multi-mechanistic effects on curbing immune suppression, angiogenesis, and tumor invasion. Additionally, LXR therapy may augment anti-tumor responses when given in combination with checkpoint inhibitors or adoptive T cell therapies or may render patients who are refractory to these immunotherapies responsive.[1]
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| Molecular Formula |
C34H34CL2F3NO3
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| Molecular Weight |
632.54
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| Exact Mass |
631.186
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| Elemental Analysis |
C, 64.56; H, 5.42; Cl, 11.21; F, 9.01; N, 2.21; O, 7.59
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| CAS # |
610318-03-1
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| Related CAS # |
RGX-104;610318-54-2; 610318-03-1 (HCl); 2648455-06-3 (zinc)
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| PubChem CID |
68861574
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
43
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| Complexity |
783
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1C=CC(C(C2=CC=CC=C2)CN(CC2C=CC=C(C=2Cl)C(F)(F)F)[C@H](C)CCOC2=CC(=CC=C2)CC(=O)O)=CC=1.Cl
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| InChi Key |
LCMIYQOJZLRHTO-GJFSDDNBSA-N
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| InChi Code |
InChI=1S/C34H33ClF3NO3.ClH/c1-24(18-19-42-29-16-8-10-25(20-29)21-32(40)41)39(22-28-15-9-17-31(33(28)35)34(36,37)38)23-30(26-11-4-2-5-12-26)27-13-6-3-7-14-27;/h2-17,20,24,30H,18-19,21-23H2,1H3,(H,40,41);1H/t24-;/m1./s1
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| Chemical Name |
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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. |
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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: ≥ 2.08 mg/mL (3.29 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: ≥ 1.5 mg/mL (2.37 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 15.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5809 mL | 7.9046 mL | 15.8093 mL | |
| 5 mM | 0.3162 mL | 1.5809 mL | 3.1619 mL | |
| 10 mM | 0.1581 mL | 0.7905 mL | 1.5809 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.
LXR Agonist Treatment Robustly Suppresses Tumor Growth and Progression across a Broad Set of Mouse and Human Tumors.Cell.2018 Feb 8;172(4):825-840.e18. |
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LXR Agonism Reduces Tumor-Infiltrating and Systemic Myeloid-Derived Suppressor Cells.Cell.2018 Feb 8;172(4):825-840.e18. |
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