| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Valosin‑containing protein (VCP/p97). KUS121 selectively inhibits the ATPase activity of VCP without interfering with other cellular VCP functions.
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| ln Vitro |
KUS121 protects neurons from cell death under oxygen and glucose deprivation (OGD) conditions by preventing ATP depletion.
In cell‑free assays, KUS121 selectively inhibits the ATPase activity of VCP. By reducing ATP consumption, it maintains cellular ATP levels, as demonstrated in various cell types. The specific IC₅0 for VCP ATPase inhibition is not provided in the available data. In H9C2 cardiomyocytes, KUS121 reduces ER stress markers (e.g., CHOP, GRP78/BiP) and improves cell viability under stress conditions. |
| ln Vivo |
KUS121 (IVT injection, 25 μg/eye) appears to exhibit better inhibition of inner retinal thinning at 7 and 14 days after ischemic injury. KUS121 (IVT injection) also has neuroprotective effects on retinal morphology and function after ischemic injury[1]. KUS121 inhibits the thinning of the outer nuclear layer and maintains visual function. KUS121 (retinal) inhibits endoplasmic reticulum stress, activates mammalian target of rapamycin, and inhibits disease-associated apoptosis[3].
In vivo, KUS121 has shown beneficial effects in multiple disease models. In a transverse aortic constriction (TAC)-induced mouse model of heart failure (HF), KUS121 administration rapidly improved left ventricular ejection fraction and improved the creatine phosphate/ATP ratio. Long‑term administration suppressed cardiac hypertrophy and fibrosis. In a canine model of high‑frequency paced HF, KUS121 improved left ventricular contractility and decreased left ventricular end‑diastolic pressure without increasing heart rate. |
| Enzyme Assay |
A general cell‑free protocol for assessing VCP ATPase activity and its inhibition by KUS121: A malachite green phosphate detection assay is used. Recombinant His‑tagged human VCP protein (100 ng) is incubated in ATPase buffer (25 mM HEPES, pH 7.5, 100 mM NaCl, 5 mM MgCl2, 1 mM DTT) with 1 mM ATP and varying concentrations of KUS121 (0.1 nM to 100 uM) at 37degC for 30 minutes. The reaction is stopped by adding malachite green reagent, and the absorbance is measured at 620 nm. The IC₅0 for ATPase inhibition is calculated from the inhibition curve.
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| Cell Assay |
A general cellular protocol for assessing the cytoprotective effects of KUS121: H9C2 rat cardiomyocytes or primary neonatal rat cardiomyocytes are seeded in 96‑well plates. The cells are treated with KUS121 (0.1, 1, 10, 50 uM) for 1 hour prior to exposure to an ER stress inducer (e.g., thapsigargin 1 uM or tunicamycin 5 ug/mL) for 24‑48 hours. Cell viability is measured using the MTT or CellTiter‑Glo assay. ATP levels are measured using a luciferase‑based ATP assay kit. ER stress markers (CHOP, GRP78, ATF4) are measured by Western blot and qRT‑PCR. Apoptosis is assessed by Annexin V/PI staining and flow cytometry, or by measuring cleaved caspase‑3 levels.
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| Animal Protocol |
General animal protocol for KUS121 in a heart failure model: Male C57BL/6J mice undergo transverse aortic constriction (TAC) surgery. Sham‑operated mice serve as controls. Two weeks after TAC, the mice are randomized into treatment groups (n=10/group). KUS121 is formulated in a suitable vehicle and administered via intraperitoneal (IP) injection at doses of 3, 10, and 30 mg/kg once daily for 4 weeks. Echocardiography is performed at baseline and at 2 and 4 weeks post‑treatment to measure left ventricular ejection fraction (LVEF), fractional shortening (FS), and left ventricular internal dimension (LVID). At the end of the study, the hearts are harvested for histology (H&E, Masson‘s trichrome for fibrosis, TUNEL for apoptosis) and for biochemical analysis (ATP levels, ER stress markers).
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| ADME/Pharmacokinetics |
General PK protocol for KUS121: Male Sprague‑Dawley rats are administered KUS121 via oral gavage (PO, 10 mg/kg) and intravenous (IV, 2 mg/kg). Blood samples are collected at 0.083, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours. Plasma concentrations are quantified by LC‑MS/MS. PK parameters (Cmax, Tmax, AUC, t½, clearance, Vd, and oral bioavailability) are calculated.
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| Toxicity/Toxicokinetics |
General toxicity protocol for KUS121: A 28‑day repeat‑dose oral toxicity study is performed in rats. KUS121 is administered via oral gavage at doses of 10, 30, and 100 mg/kg/day. Parameters include clinical signs, body weight, food consumption, ophthalmology, ECGs, hematology, serum chemistry (including cardiac troponin I, BNP), and urinalysis. At termination, a full necropsy and histopathology of major organs, with special attention to the heart, liver, and kidneys, is performed.
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| References |
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| Additional Infomation |
KUS121 is a small molecule developed at Kyoto University. A patent application has been filed related to its use for heart failure (Tokugan 2021‑211106). The compound has also shown efficacy in models of atherosclerosis (by reducing ER stress in endothelial cells) and ischemic retinal injury (by suppressing ER stress and reducing cell death). KUS121 does not increase intracellular calcium levels, differentiating it from conventional catecholamine inotropic agents, and it improves contractility without increasing heart rate.
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| Molecular Formula |
C22H16FN4NAO3S
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|---|---|
| Molecular Weight |
458.44
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| Exact Mass |
458.082
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| CAS # |
1357164-52-3
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| PubChem CID |
56955396
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| Appearance |
Solid powder
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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 |
4
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| Heavy Atom Count |
32
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| Complexity |
752
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O[C@@]12C(C3C=C(C)C=CC=3N=C1N(C1C=CC=CC=1)CC2)=O
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| InChi Key |
OEEZHMGRDYLKGJ-UHFFFAOYSA-M
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| InChi Code |
InChI=1S/C22H17FN4O3S.Na/c1-13-10-14(23)6-8-16(13)19-9-7-15(12-25-19)26-27-20-11-21(31(28,29)30)17-4-2-3-5-18(17)22(20)24;/h2-12H,24H2,1H3,(H,28,29,30);/q;+1/p-1
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| Chemical Name |
sodium;4-amino-3-[[6-(4-fluoro-2-methylphenyl)pyridin-3-yl]diazenyl]naphthalene-1-sulfonate
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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. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1813 mL | 10.9066 mL | 21.8131 mL | |
| 5 mM | 0.4363 mL | 2.1813 mL | 4.3626 mL | |
| 10 mM | 0.2181 mL | 1.0907 mL | 2.1813 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.
Link: https://clinicaltrials.gov/ct2/show/NCT06178055
Conditions:Central Retinal Artery OcclusionProducts are for research use only; We do not sell to patients
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