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| 5mg |
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| Targets |
Supinoxin targets phosphorylated-p68 RNA helicase (P-p68), also known as Y593-phosphorylated DDX5. It binds to Y593-phosphorylated DDX5 with a Kd of ~19 nM, but does not interact with unphosphorylated DDX5. It selectively inhibits β-catenin-dependent ATPase activity over RNA-dependent ATPase activity at 0.2 µM. By inhibiting P-p68, supinoxin blocks the NF-κB pathway, leading to reduced tumor growth and metastasis.
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| ln Vitro |
RX-5902 (0–10 μM; 72 hours) exhibits activity against TNBC cell lines of all molecular subtypes, as well as against cell lines exhibiting PTEN deletion, p53, RB1, and CDKN2A mutations [1]. tetraploid cells increased quantitatively as a result of nM; 24 hours) treatment, which is compatible with the stimulation of G2–M cell cycle signaling [1]. Cell lines resistant to RX-5902's antiproliferative effects did not exhibit substantial cellular activation in response to RX-5902 (0-100 nM; 72 hours). However, the observed cellular activation in sensitive cells began between 24 and 48 hours and peaked at 72 hours. In TNBC cell lines susceptible to RX-5902 at 100 nM dosages, the adsorbable inducible cellular agent RX-5902 (0-100 nM; 24 or 48 hours) decreases MCL-1 expression in a dose-dependent manner [1]. MDA and RX-5902 both suppress cell proliferation. -IC50 values for HepG2, PC-3, U251, HeLa, SK-MEL-28, A549, MKN-45, Caki-1, UMRC2, PANC-1, MB-231, and HepG2 range from 0.01 to
Supinoxin is an orally active inhibitor of phosphorylated-p68 RNA helicase (P-p68). It induces cell apoptosis and inhibits the growth of TNBC cancer cell lines with IC50s of 10-20 nM. It has shown promise as an anti-inflammatory and anticancer agent. Supinoxin binds to Y593-phosphorylated DDX5 with a Kd of ~19 nM. |
| ln Vivo |
In the MDA-MB-231 model, RX-5902 (powder coating; 160/320/600 mg/kg; once weekly for three weeks) demonstrated a strong dose-dependent tumor growth inhibition (TGI), with TGIs of 55.7, respectively %, 80.29%, and 94.58% at 160 mg/kg, 320 mg/kg, and 600 mg/kg. It outperforms the chemotherapeutic medication nab-paclitaxel (TGI 45%) [1]. Model of mice xenograft MDAMD-231 [1]
Supinoxin is an orally active inhibitor of phosphorylated-p68 RNA helicase (P-p68). It has shown promise as an anti-inflammatory and anticancer agent. It can block the NF-κB pathway, leading to reduced tumor growth, metastasis, and inflammatory responses. It has been studied for the treatment of triple-negative breast cancer. |
| Enzyme Assay |
Supinoxin is a P-p68 inhibitor, and its in vitro activity is assessed in binding and cell-based assays. In binding assays, the compound is incubated with Y593-phosphorylated DDX5, and the binding affinity (Kd) is measured. In cell-based assays, the effect on cell viability, apoptosis, and signaling pathways is measured.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: MDA-MB-231, HCC1806, Hs578t, CAL-85-1, HCC38, HCC1187, MDA-MB-436, CAL- μM to 0.021 μM, growth inhibitory dye[2]. 51. HCC38, BT549, MDAMB-157, HDQ-P1, HCC1395, MDA-MB-436, HCC1937, CAL-120, BT20 Cell Tested Concentrations: 0-10 μM Incubation Duration: 72 hrs (hours) Experimental Results: Displays the average IC50 of cells versus RX -5902 treats cell lines sensitive to 56 nM. Cell cycle analysis[1] Cell Types: sensitive (MDA-MB-231 and HCT1806) and two resistant (MDA-MB-436 and CAL-120) cell lines Tested Concentrations: 20 nM; 100 nM Incubation Duration: 24 hrs (hours) Experimental Results: Causes cell cycle arrest of sensitive cells G2-M. Apoptosis analysis[1] Cell Types: sensitive (MDA-MB-231 and HCT1806) and two resistant (MDA-MB-436 and CAL-120) cell lines Tested Concentrations: 0-100 nM Incubation Duration: 24-72 Hourly Experimental Results: Induction of apoptosis in sensitive cell lines peaked at 72 hrs (hours). Western Blot Analysis[1] Cell Types: Cal-51, HCC-1806 and MDA-MB-468 Cell Tested Concentrations: 20 nM; 100 nM Incubation Duration: 24 hou Supinoxin is dissolved in DMSO and applied to cultured cancer cells at concentrations ranging from 1 nM to 10 µM. The effect on cell viability is assessed using MTT assays. Apoptosis is measured using flow cytometry or caspase activity assays. The inhibition of NF-κB signaling is assessed by Western blotting. |
| Animal Protocol |
Animal/Disease Models: MDAMD-231 xenograft model in mice[1]
Doses: 160 mg/kg; 320 mg/kg; 600 mg/kg Route of Administration: Oral administration; once weekly for 3 weeks Experimental Results:diminished tumor volume as a dose-dependent manner. |
| ADME/Pharmacokinetics |
Supinoxin has a molecular weight of 441.46 g/mol and a molecular formula of C22H24FN5O4. It is an orally active compound. The compound is typically stored as a powder at -20°C for long-term stability. Supinoxin is also known as RX-5902.
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| Toxicity/Toxicokinetics |
Supinoxin has a manageable toxicity profile. Common side effects may include gastrointestinal disturbances, fatigue, and hematological toxicities. No significant hepatotoxicity or nephrotoxicity has been reported.
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| References |
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| Additional Infomation |
RX-5902, a P-p68 inhibitor, is a small-molecule phosphorylated p68 RNA helicase (P-p68) inhibitor with high oral bioavailability and potential antiproliferative and antitumor activities. After oral administration, RX-5902 inhibits the activity of the anti-apoptotic protein Bcl-2 and promotes the induction of cyclin-dependent kinase inhibitor 1 (p21). This may prevent the progression of the G2/M phase of the cell cycle, thereby inhibiting tumor cell growth. P-p68 is overexpressed in various solid tumors but not in normal tissues and plays a role in tumor progression and metastasis. p21 is a potent cyclin-dependent kinase inhibitor that regulates cell cycle progression and mediates cell arrest and senescence.
Supinoxin is an orally active inhibitor of phosphorylated-p68 RNA helicase (P-p68) and a potent first-in-class anti-cancer agent. Supinoxin interacts with Y593-phosphorylated p68. It binds to Y593-phosphorylated DDX5 with a Kd of ~19 nM. Supinoxin induces cell apoptosis and inhibits the growth of TNBC cancer cell lines with IC50s of 10-20 nM. It has shown promise as an anti-inflammatory and anticancer agent. |
| Molecular Formula |
C22H24FN5O4
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|---|---|
| Molecular Weight |
441.455468177795
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| Exact Mass |
441.181
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| CAS # |
888478-45-3
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| PubChem CID |
11619093
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| Appearance |
White to off-white solid powder
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| LogP |
2.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
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| Complexity |
611
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(N1CCN(C2C=C(OC)C=C(OC)C=2)CC1)NC1C(OC)=NC2C(=CC(=CC=2)F)N=1
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| InChi Key |
KAKPGJJRYRYSTP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H24FN5O4/c1-30-16-11-15(12-17(13-16)31-2)27-6-8-28(9-7-27)22(29)26-20-21(32-3)25-18-5-4-14(23)10-19(18)24-20/h4-5,10-13H,6-9H2,1-3H3,(H,24,26,29)
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| Chemical Name |
4-(3,5-dimethoxyphenyl)-N-(7-fluoro-3-methoxyquinoxalin-2-yl)piperazine-1-carboxamide
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| Synonyms |
RX5902; RX5902; Supinoxin
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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 : ~100 mg/mL (~226.52 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.66 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 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.66 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2652 mL | 11.3261 mL | 22.6521 mL | |
| 5 mM | 0.4530 mL | 2.2652 mL | 4.5304 mL | |
| 10 mM | 0.2265 mL | 1.1326 mL | 2.2652 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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