| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Targets |
Akt
The primary target of K-80003 is the retinoid X receptor-alpha (RXRα), specifically the truncated form known as tRXRα. tRXRα is a splice variant or proteolytic fragment of RXRα that lacks part of the N-terminal domain and is frequently overexpressed in cancer cells. Unlike full-length RXRα, which functions as a nuclear receptor, tRXRα can translocate to the cytoplasm and interact with the p85α regulatory subunit of PI3K. This interaction leads to the activation of the PI3K/Akt signaling pathway, which promotes tumor cell survival, proliferation, and migration. K-80003 binds to RXRα with high affinity but does not inhibit COX activity, distinguishing it from traditional NSAIDs. By binding to tRXRα, K-80003 stabilizes its tetrameric form and promotes its nuclear localization, thereby preventing its interaction with p85α in the cytoplasm. This disrupts tRXRα-dependent Akt activation and inhibits tumor cell growth. |
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| ln Vitro |
K-80003 inhibits TNF-induced colocalization of tRXRα with p85α in the cytoplasm, leading to tRXRα nuclear localization, in MCF-7 cells. Western blotting demonstrates that the tRXRα monomer is distributed in both the nuclear and cytoplasmic fractions while the K-80003-stabilized tetrameric form of tRXRα is only found in the nuclear fraction[2].
K-80003 demonstrates potent in vitro activity as an inhibitor of tRXRα-dependent Akt activation and tumor cell growth. In cellular assays, K-80003 (5 μM) has been shown to inhibit TNF-induced colocalization of tRXRα with p85α in the cytoplasm of MCF-7 breast cancer cells, leading to the nuclear localization of tRXRα. Western blotting analysis has demonstrated that the tRXRα monomer is distributed in both the nuclear and cytoplasmic fractions, while the K-80003-stabilized tetrameric form of tRXRα is only found in the nuclear fraction. This redistribution of tRXRα from the cytoplasm to the nucleus disrupts its interaction with p85α and inhibits Akt activation. The compound's high affinity for RXRα and its lack of COX inhibitory activity make it a selective and valuable tool for studying RXRα-mediated signaling in cancer. |
| ln Vivo |
K-80003 is a potent inhibitor of AKT activation by all-trans-retinoic acid. Inhibiting tRXRα-dependent AKT activation and tRXRα tumor growth in animals with K-80003 shows improved efficacy. Despite lacking COX inhibitory activity, K-80003 has a high affinity for RXRα[1].
In vivo, K-80003 has shown improved efficacy in inhibiting tRXRα-dependent Akt activation and tRXRα tumor growth in animal models. In a xenograft model using nude mice (BALB/c, 4-5 weeks old), K-80003 was administered by intraperitoneal injection every other day for a total of six injections following tumor cell transplantation. Tumor sizes and body weights were measured every 4 days. The compound effectively inhibited tumor growth, demonstrating its potential as an anti-cancer agent. Despite lacking COX inhibitory activity, K-80003's high affinity for RXRα and its ability to modulate tRXRα localization and signaling contribute to its anti-tumor efficacy. |
| Enzyme Assay |
In vitro biochemical assays for K-80003 are focused on studying its interaction with RXRα and its effects on tRXRα localization and signaling. Binding affinity assays, such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC), can be used to measure the compound's binding to RXRα. Cellular fractionation assays, combined with western blotting, are used to assess the distribution of tRXRα in the nuclear and cytoplasmic fractions following treatment with K-80003. Co-immunoprecipitation (Co-IP) experiments can be performed to evaluate the interaction between tRXRα and p85α and to determine whether K-80003 disrupts this interaction. These assays provide mechanistic insights into the compound's mode of action.
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| Cell Assay |
K-80003 (5 μM) is pretreated with or without for 3 hours before TNF (10 ng/mL) is applied to MCF-7 cells that have been cotransfected with Myc-RXRα, Myc-tRXRα, tRXRα/L433D and p85α.
Anti-Myc and anti-p85α antibodies are used to stain the cells, and confocal microscopy is used to determine where in the cell they are located. K-80003 (5 μM) is administered to or left untreated for 6 hours to HEK293T cells that have been cotransfected with Myc-tRXRα . By using an anti-Myc antibody and western blotting to analyze the nuclear (N) and cytoplasmic (C) fractions after BS3 crosslinking. Examining the expression of cytoplasmic -tubulin and nuclear PARP in non-crosslinked fractions allows one to determine the purity of the fractions. The first of three related experiments is displayed[2].
In vitro cell-based assays for K-80003 are used to evaluate its effects on cell signaling, proliferation, and survival. A common assay involves treating cancer cell lines (e.g., MCF-7 breast cancer cells) with the compound and measuring the phosphorylation of Akt and its downstream targets by western blotting to confirm inhibition of the PI3K/Akt pathway. Cell proliferation is assessed using assays such as MTT, CellTiter-Glo, or [³H]-thymidine incorporation. Apoptosis is measured by detecting caspase-3/7 activity or by using Annexin V staining and flow cytometry. Additionally, the compound's effects on cell migration and invasion can be evaluated using wound healing or Boyden chamber assays. These assays provide a comprehensive view of the compound's cellular activity. |
| Animal Protocol |
Mice[1]: Subcutaneous injection of 100 L of cells (2106) is performed on naked mice (BALB/c, 4-5 weeks old). Mice (n=6) are given intraperitoneal injections of K-80003, Sulindac, or corn oil once every other day (total of six injections) for a period of seven days following transplantation. Every 4 days, measurements are made of the body weight and tumor sizes.
In vivo animal studies for K-80003 are typically conducted in xenograft models of cancer. In a typical study, immunocompromised mice are implanted subcutaneously with human tumor cells (e.g., MCF-7 or other cancer cell lines). When tumors reach a certain size, mice are randomized into treatment groups and administered K-80003 by intraperitoneal injection. Tumor volume is measured regularly using calipers, and tumor weight is recorded at the end of the study. Body weight is monitored to assess toxicity. Pharmacodynamic endpoints, such as the phosphorylation of Akt in tumor tissue, are measured to confirm target engagement. These studies provide critical data on the compound's anti-tumor efficacy and its mechanism of action in vivo. |
| ADME/Pharmacokinetics |
The pharmacokinetic (PK) properties of K-80003 are not extensively detailed in the available sources. The compound has a molecular weight of 336.40 and a molecular formula of C₂₂H₂₁FO₂. It is supplied as a light yellow to yellow solid with a purity of ≥98%. For research use, it is typically stored as a powder at -20°C for up to three years or in solution at -80°C for up to one year. Detailed PK parameters, such as half-life, clearance, volume of distribution, and oral bioavailability, are not specified but would be determined in standard preclinical PK studies.
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| Toxicity/Toxicokinetics |
The toxicological profile of K-80003 is not extensively documented in publicly available sources. As a research compound, its safety profile would be evaluated in preclinical studies, including general toxicity, genotoxicity, and organ-specific toxicity assessments. For laboratory handling, standard safety precautions for research chemicals should be observed, including the use of personal protective equipment (gloves, lab coat, safety goggles) and working in a well-ventilated area. The compound is intended for research use only and is not for human therapeutic or diagnostic use.
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| References | |
| Additional Infomation |
[5-Fluoro-1-(4-Isopropylbenzyl)-2-methylinden-3-yl]acetic acid is a sulindac-based nonsteroidal anti-inflammatory drug (NSAID). It exhibits NSAID activity. Its structure is related to that of acetic acid.
K-80003 is a research-grade compound also known as TX-803. Its IUPAC name is (Z)-2-(5-fluoro-1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl)acetic acid. It has a molecular formula of C₂₂H₂₁FO₂ and a molecular weight of 336.40. The compound is a sulindac-based non-steroidal anti-inflammatory drug (NSAID) derivative that functions as a regulator of RXRα. Unlike traditional NSAIDs, K-80003 does not inhibit COX activity but instead binds to RXRα with high affinity. K-80003 is a valuable tool for studying RXRα-mediated signaling, particularly the role of tRXRα in cancer, and for evaluating the therapeutic potential of targeting this pathway. |
| Molecular Formula |
C22H21FO2
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|---|---|
| Molecular Weight |
336.399349927902
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| Exact Mass |
336.152
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| Elemental Analysis |
C, 78.55; H, 6.29; F, 5.65; O, 9.51
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| CAS # |
1292821-90-9
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| Related CAS # |
1292821-90-9
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| PubChem CID |
46224594
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
491.6±40.0 °C at 760 mmHg
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| Flash Point |
251.1±27.3 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.615
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| LogP |
6.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
567
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(=C/C2=CC=C(C(C)C)C=C2)/C2=C(C=C(F)C=C2)C(CC(O)=O)=C/1C
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| InChi Key |
QCXBVGNDRYQVJO-GRSHGNNSSA-N
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| InChi Code |
InChI=1S/C22H21FO2/c1-13(2)16-6-4-15(5-7-16)10-19-14(3)20(12-22(24)25)21-11-17(23)8-9-18(19)21/h4-11,13H,12H2,1-3H3,(H,24,25)/b19-10-
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| Chemical Name |
1H-Indene-3-acetic acid, 5-fluoro-2-methyl-1-((4-(1-methylethyl)phenyl)methylene)-, (1Z)-
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| Synonyms |
K 80003; K-80003; K80003
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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 |
| 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: ~30 mg/mL (89.2 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (8.92 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 30.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9727 mL | 14.8633 mL | 29.7265 mL | |
| 5 mM | 0.5945 mL | 2.9727 mL | 5.9453 mL | |
| 10 mM | 0.2973 mL | 1.4863 mL | 2.9727 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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