Synonym
Abequolixron, RGX-104 hydrochloride; RGX-104 HCl; RGX-104; RGX104; RGX 104; SB742881; SB-742881; SB 742881;
IUPAC/Chemical Name
(R)-2-[3-[3-[[2-Chloro-3-(trifluoromethyl)benzyl](2,2-diphenylethyl)amino]-3-methylpropoxy]phenyl]acetic acid hydrochloride
InChi Key
LCMIYQOJZLRHTO-GJFSDDNBSA-N
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
SMILES Code
O=C(O)CC1=CC=CC(OCC[C@H](N(CC2=CC=CC(C(F)(F)F)=C2Cl)CC(C3=CC=CC=C3)C4=CC=CC=C4)C)=C1.[H]Cl
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
LXRbeta, a member of the oxysterol receptor family, which is in the nuclear receptor family of transcription factors, plays a key role in cholesterol transport, glucose metabolism and the modulation of inflammatory responses; activation of LXRbeta suppresses tumor cell invasion, angiogenesis, tumor progression, and metastasis in a variety of tumor cell types. The expression of the ApoE protein becomes silenced in human cancers as they grow, become invasive, and metastasize; ApoE silencing is related to reduced survival in cancer patients. The LXR-ApoE pathway regulates the ability of cancers to evade the immune system and recruit blood vessels.
Biological target:
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, tumor cells and endothelial cells in the tumor microenvironment. This reverses immune evasion, enhances anti-tumor immune responses and inhibits proliferation of tumor cells.
In vitro activity:
RGX-104 remodels the acidic tumor microenvironment by transcriptional activation of ApoE to regress myeloid-derived suppressor cells' (MDSCs) activity, which neatly creates foreshadowing for intensifying pyroptosis. RNA-seq analysis of MRC at the cellular level reveals 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.
Reference: Adv Healthc Mater. 2022 Nov;11(21):e2201233. https://pubmed.ncbi.nlm.nih.gov/36049144/
In vivo activity:
This study aimed to design a dual-pH-sensitivity conjugated micelle system (PAH/RGX-104@PDM/PTX) that could deliver RGX-104 and paclitaxel (PTX) to the perivascular region and tumor cells. Results suggest that the codelivery nanocarrier not only cause apoptosis of cancer cells but also regulate the tumor immune environment to ultimately enhance the antitumor effect of CTLs through MDSCs depletion.
Reference: J Control Release. 2020 Jan 10;317:43-56. https://pubmed.ncbi.nlm.nih.gov/31758970/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
150.0 |
237.14 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
632.56
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Qiu W, Su W, Xu J, Liang M, Ma X, Xue P, Kang Y, Sun ZJ, Xu Z. Immunomodulatory-Photodynamic Nanostimulators for Invoking Pyroptosis to Augment Tumor Immunotherapy. Adv Healthc Mater. 2022 Nov;11(21):e2201233. doi: 10.1002/adhm.202201233. Epub 2022 Sep 13. PMID: 36049144.
2. Liang H, Shen X. LXR activation radiosensitizes non-small cell lung cancer by restricting myeloid-derived suppressor cells. Biochem Biophys Res Commun. 2020 Jul 23;528(2):330-335. doi: 10.1016/j.bbrc.2020.04.137. Epub 2020 May 22. PMID: 32448508.
3. Wan D, Yang Y, Liu Y, Cun X, Li M, Xu S, Zhao W, Xiang Y, Qiu Y, Yu Q, Tang X, Zhang Z, He Q. Sequential depletion of myeloid-derived suppressor cells and tumor cells with a dual-pH-sensitive conjugated micelle system for cancer chemoimmunotherapy. J Control Release. 2020 Jan 10;317:43-56. doi: 10.1016/j.jconrel.2019.11.011. Epub 2019 Nov 20. PMID: 31758970.
In vitro protocol:
1. Qiu W, Su W, Xu J, Liang M, Ma X, Xue P, Kang Y, Sun ZJ, Xu Z. Immunomodulatory-Photodynamic Nanostimulators for Invoking Pyroptosis to Augment Tumor Immunotherapy. Adv Healthc Mater. 2022 Nov;11(21):e2201233. doi: 10.1002/adhm.202201233. Epub 2022 Sep 13. PMID: 36049144.
2. Liang H, Shen X. LXR activation radiosensitizes non-small cell lung cancer by restricting myeloid-derived suppressor cells. Biochem Biophys Res Commun. 2020 Jul 23;528(2):330-335. doi: 10.1016/j.bbrc.2020.04.137. Epub 2020 May 22. PMID: 32448508.
In vivo protocol:
1. Liang H, Shen X. LXR activation radiosensitizes non-small cell lung cancer by restricting myeloid-derived suppressor cells. Biochem Biophys Res Commun. 2020 Jul 23;528(2):330-335. doi: 10.1016/j.bbrc.2020.04.137. Epub 2020 May 22. PMID: 32448508.
2. Wan D, Yang Y, Liu Y, Cun X, Li M, Xu S, Zhao W, Xiang Y, Qiu Y, Yu Q, Tang X, Zhang Z, He Q. Sequential depletion of myeloid-derived suppressor cells and tumor cells with a dual-pH-sensitive conjugated micelle system for cancer chemoimmunotherapy. J Control Release. 2020 Jan 10;317:43-56. doi: 10.1016/j.jconrel.2019.11.011. Epub 2019 Nov 20. PMID: 31758970.
1: Li X, Liang X, Fu W, Luo R, Zhang M, Kou X, Zhang Y, Li Y, Huang D, You Y, Wu Q, Gong C. Reversing cancer immunoediting phases with a tumor-activated and optically reinforced immunoscaffold. Bioact Mater. 2024 Feb 3;35:228-241. doi: 10.1016/j.bioactmat.2024.01.026. PMID: 38333614; PMCID: PMC10850754.
2: Qiu W, Su W, Xu J, Liang M, Ma X, Xue P, Kang Y, Sun ZJ, Xu Z. Immunomodulatory-Photodynamic Nanostimulators for Invoking Pyroptosis to Augment Tumor Immunotherapy. Adv Healthc Mater. 2022 Nov;11(21):e2201233. doi: 10.1002/adhm.202201233. Epub 2022 Sep 13. PMID: 36049144.
3: Liang H, Shen X. LXR activation radiosensitizes non-small cell lung cancer by restricting myeloid-derived suppressor cells. Biochem Biophys Res Commun. 2020 Jul 23;528(2):330-335. doi: 10.1016/j.bbrc.2020.04.137. Epub 2020 May 22. PMID: 32448508.
4: Wan D, Yang Y, Liu Y, Cun X, Li M, Xu S, Zhao W, Xiang Y, Qiu Y, Yu Q, Tang X, Zhang Z, He Q. Sequential depletion of myeloid-derived suppressor cells and tumor cells with a dual-pH-sensitive conjugated micelle system for cancer chemoimmunotherapy. J Control Release. 2020 Jan 10;317:43-56. doi: 10.1016/j.jconrel.2019.11.011. Epub 2019 Nov 20. PMID: 31758970.
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