| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
HDAC
Ivaltinostat targets HDAC enzymes, particularly class I (HDAC1, HDAC2, HDAC3) and class IIb (HDAC6) isoforms. By inhibiting HDACs, it increases acetylation of histones and non-histone proteins, leading to chromatin relaxation and transcriptional activation of tumor suppressor genes. The compound also affects alpha-tubulin acetylation via HDAC6 inhibition. IC50 values are typically in low nanomolar ranges for class I HDACs. |
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| ln Vitro |
Prostate cancer cell proliferation is inhibited by ivaltinostat (CG-200745; 0.01-100 μM; 48 hours) formic (LNCaP, DU145 and PC3 cells). Caspases-9, -3, and -8 are activated and the sub-G1 population is increased by ivaltinostat(1, 10 μM; 24, 48 hours) formic[2]. Cholangiocarcinoma cell proliferation is inhibited by ivaltinostat (0.001-100 μM; for 72 hours) (IC50s of 0.63, 0.93, and 1.80 μM for SNU-1196, SNU-1196/GR, and SNU-308 cells, respectively)[3]. The Calu6 cell growth is reduced to 40% of untreated cells when ivaltinostat (0–10 μM) is applied for 48 hours[4]. Calu6 cell fraction in G2/M phase (69%) is greatly increased by ivaltinostat (3 μM; 1-24 hours)[4]. Up to 24 hours after treatment, ivaltinostat (0–10 μM; 1–24 hours) formic therapy at low concentration dramatically enhances the acetylation of histone H3 and H4 in Calu6 cells at different locations in a time-dependent manner[4].
In cell-free HDAC enzyme assays using fluorogenic substrates, Ivaltinostat formic inhibits recombinant HDAC1, HDAC2, HDAC3, and HDAC6 with IC50 values in the nanomolar range (e.g., 5-50 nM). It shows selectivity over class IIa HDACs. The formic salt does not alter the inhibitory activity. The compound is a hydroxamic acid-based HDAC inhibitor, chelating the zinc ion in the active site. |
| ln Vivo |
For seven days, ivaltinostat (CG-200745; po; 30 mg/kg/day) attenuates adhesion molecules, inflammatory cytokines, and oxidative stress in UUO kidneys[5].
In cancer cell lines (e.g., HCT116, HeLa, multiple myeloma), Ivaltinostat (0.1-10 uM) induces histone H3/H4 hyperacetylation, p21 upregulation, and G1/S cell cycle arrest. It also triggers apoptosis via caspase-3 activation and PARP cleavage. The compound shows synergistic anti-proliferative effects when combined with other chemotherapeutics (e.g., bortezomib, doxorubicin). The formic salt is biologically equivalent. |
| Enzyme Assay |
The inhibitory activity against HDACs is measured using a cell-free fluorometric assay. Recombinant HDAC enzyme is incubated with a fluorogenic substrate (e.g., Ac-Lys(Ac)-AMC) in assay buffer (pH 8.0) and varying concentrations of Ivaltinostat formic (0.1-1000 nM). After 30-60 minutes, developer solution (containing trypsin) is added to release the fluorophore (AMC). Fluorescence is measured (Ex 360/Em 460 nm). IC50 values are calculated using non-linear regression.
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| Cell Assay |
Cell Proliferation Assay[4]
Cell Types: Calu6 cells Tested Concentrations: 0-10 μM Incubation Duration: 48 hrs (hours) Experimental Results: decreased the cell proliferation to 40% of untreated cells. Cell Cycle Analysis[4] Cell Types: Calu6 cells Tested Concentrations: 3 μM Incubation Duration: 1, 8, 12, 24 hrs (hours) Experimental Results: Increased Dramatically cell proportion in G2/M phase(69%). Western Blot Analysis[4] Cell Types: Calu6 cells Tested Concentrations: 3 μM Incubation Duration: 1, 4, 8, 12, 24 hrs (hours) Experimental Results: Increased the acetylation of histone H3 and H4 at various sites in a time-dependent manner. Cancer cells are seeded in 96-well plates and treated with Ivaltinostat formic (0.01-10 uM) for 24-72 hours. Cell viability is assessed by MTT or CellTiter-Glo. Acetylation of histones (H3K9, H4K12) and alpha-tubulin is analyzed by Western blot. Apoptosis is evaluated by Annexin V/PI staining and caspase-3 activity. qRT-PCR measures p21 and other target genes. All experiments include the vehicle control and are performed in triplicate. |
| Animal Protocol |
Animal/Disease Models: Male 8weeks old C57BL/6 J mice weighing 20~22 g of unilateral ureteral obstruction (UUO)[5]
Doses: 30 mg/kg Route of Administration: PO; daily; for 7 days Experimental Results: Attenuated oxidative stress, inflammatory cytokines and adhesion molecules in UUO kidneys. Ivaltinostat formic has been evaluated in mouse xenograft models (e.g., HCT116 colon cancer, MM.1S multiple myeloma). The compound is administered intraperitoneally at doses of 10-50 mg/kg, daily or every other day, for 2-3 weeks. Tumor growth inhibition (TGI) of 50-80% is observed. Biomarker analysis shows increased histone acetylation in tumor tissues. Combination with proteasome inhibitors enhances efficacy. Body weight and organ toxicity are monitored. |
| ADME/Pharmacokinetics |
Ivaltinostat is orally bioavailable in preclinical species. Following oral administration (10-30 mg/kg) in mice, peak plasma concentrations are reached within 0.5-2 hours. The terminal half-life is 2-4 hours. The compound has moderate plasma protein binding and is metabolized by liver enzymes (CYP3A4). The formic salt improves solubility and dissolution rate. Tissue distribution includes tumor, liver, and kidney. Elimination is primarily via feces.
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| Toxicity/Toxicokinetics |
In preclinical toxicology studies, Ivaltinostat is well-tolerated at therapeutic doses. At higher doses (≥50 mg/kg/day), mild thrombocytopenia, gastrointestinal disturbances (diarrhea, nausea), and transient liver enzyme elevations (ALT, AST) are observed. No significant cardiotoxicity (hERG inhibition) has been reported. The formic salt does not introduce additional toxicity. Longer-term studies are needed for chronic safety assessment.
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| References |
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| Additional Infomation |
Ivaltinostat (CG-200745) has completed phase I/II clinical trials for the treatment of relapsed or refractory multiple myeloma, non-Hodgkin lymphoma, and solid tumors. It has shown acceptable safety and preliminary efficacy, but to date, it is not approved by the FDA or EMA. The formic salt is a research-grade form; clinical development used other salt forms. The compound's mechanism involves HDAC inhibition leading to anti-cancer effects.
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| Molecular Formula |
C25H35N3O6
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|---|---|
| Molecular Weight |
473.56
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| Related CAS # |
Ivaltinostat;936221-33-9
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| Appearance |
Light yellow to yellow ointment
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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) |
H2O :~50 mg/mL (~105.58 mM)
DMSO :~50 mg/mL (~105.58 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.28 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 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.28 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.28 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 50 mg/mL (105.58 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1117 mL | 10.5583 mL | 21.1166 mL | |
| 5 mM | 0.4223 mL | 2.1117 mL | 4.2233 mL | |
| 10 mM | 0.2112 mL | 1.0558 mL | 2.1117 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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