Size | Price | |
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100mg | ||
250mg | ||
500mg | ||
Other Sizes |
Targets |
HDAC1 2.2 nM (IC50) HDAC2 5.1 nM (IC50) HDAC3 5.2 nM (IC50) HDAC6 85.5 nM (IC50) HDAC8 29.9 nM (IC50) Plasmodium
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ln Vitro |
Compound JX35, HDAC1-IN-3, exhibits antimalarial action against wild-type Plasmodium falciparum (P. falciparum) parasite 3D7 and chloroquine-resistant P. falciparum parasite Dd2, respectively, with IC50s of 1.26 nM and 1.61 nM[1]. HDAC1-IN-3 (10 µM; 72 h) exhibits negligible cytotoxicity, with IC50s for HepG2 and 293T cells of 1.02 µM and 1.21 µM, respectively[1]. Using clinical antimalarial medications, HDAC1-IN-3 (72 h) exhibits no cross-resistance, with IC50s of 3.06, 2.18, and 5.85 nM for GB4, C2A, and CP286 respectively[1]. With asynchronous 3D7 parasites, HDAC1-IN-3 (10, 30, 60, 100 nM; 3, 6, 12, 24 h) exhibits antimalarial action in a time- and dose-dependent manner[1]. The lethal effects of JX35 on P. falciparum parasites during asexual reproduction phases are demonstrated by HDAC1-IN-3 (40 nM, 4 days; P. falciparum 3D7 cells). This action may be associated to the prevention of schizont growth and reinvasion of RBCs (red blood cells)[1]. Inhibiting the expression of Pf HDAC against ART (artemisinin)-resistant parasite strains, HDAC1-IN-3 (5, 20 nM; 4 h)[1]. With IC50s of 2.2, 5.1, 5.2, 85.5, and 29.9 nM for HDAC1, HDAC2, HDAC3, HDAC6, and HDAC8, respectively, HDAC1-IN-3 lessens the inhibition of hHDACs[1].
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ln Vivo |
HDAC1-IN-3 exhibits respectable therapeutic effectiveness and safety (30, 60, and 90 mg/kg; ip; once daily for five days)[1]. Good pharmacokinetic qualities are demonstrated by HDAC1-IN-3 (5 mg/kg; ip)[1]. HDAC1-IN-3 Pharmacokinetic Parameters in Female BALB/c Mice[1]. parameter JX35 Cmax (ng/mL) 539 Tmax (h) 0.25 AUC last (h·ng/mL) 638 AUC inf (h ·ng/mL) 640 t1/2 (h) 0.91 CLZ/F (L/h/kg) 7.81 VZ/F (L/kg) 10.20 Female BALB/c mice; 5 mg/kg; ip
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Cell Assay |
Cell Cytotoxicity Assay[1]
Cell Types: HepG2, 293T cells Tested Concentrations: 10 µM Incubation Duration: 72 h Experimental Results: demonstrated low cytotoxicity with IC50s of 1.02 µM and 1.21 µM for HepG2, 293T cells, respectively. Western Blot Analysis[1] Cell Types: P. falciparum 3D7 cells Tested Concentrations: 5, 20 nM Incubation Duration: 4 h Experimental Results: Inhibited the expression of Pf HDAC against ART (artemisinin)-resistant parasite strains. |
Animal Protocol |
Animal/Disease Models: 6- 8 weeks, BALB/c female mice[1]
Doses: 30, 60, 90 mg/kg Route of Administration: Ip, one time/day for 5 days Experimental Results: demonstrated acceptable therapeutic efficacy and safety. Animal/Disease Models: 6-8 weeks, female BALB/ c mice[1] Doses: 5 mg/kg Route of Administration: Ip Experimental Results: demonstrated good pharmacokinetic/PK properties. |
References |
[1]. Wang M, et al. Drug Repurposing of Quisinostat to Discover Novel Plasmodium falciparum HDAC1 Inhibitors with Enhanced Triple-Stage Antimalarial Activity and Improved Safety. J Med Chem. 2022; 65(5):4156-4181.
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Molecular Formula |
C22H24CLN7O2
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Molecular Weight |
453.92
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CAS # |
2482998-35-4
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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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) |
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 | 2.2030 mL | 11.0152 mL | 22.0303 mL | |
5 mM | 0.4406 mL | 2.2030 mL | 4.4061 mL | |
10 mM | 0.2203 mL | 1.1015 mL | 2.2030 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.