Size | Price | Stock | Qty |
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50mg |
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100mg |
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250mg |
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500mg |
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Other Sizes |
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Purity: ≥98%
SKLB-23bb (HDAC6-IN-1; 23bb) is a novel, potent, orally bioavailable and selective inhibitor for histone deacetylase 6 (HDAC6) with anticancer, anti-mitotic/antitubulin and neuroprotective effects. It exhibits selectivity towards HDAC1 (IC50=422 nM) and HDAC8 (IC50=3398 nM) of 25 and 200 fold, respectively, and inhibits HDAC6 with an IC50 of 17 nM. Additionally capable of disrupting microtubules is SKLB-23bb. When tested on a panel of cancer cell lines in vitro, 23bb showed low nanomolar antiproliferative effects. The increased α-tubulin acetylation level caused by 23bb was further confirmed in vitro by Western blot analysis. With an oral bioavailability of 47.0% in rats, 23bb exhibits a favorable pharmacokinetic profile. 23bb more successfully inhibited the tumor growth than SAHA, even at a 4-fold reduced dose, or ACY-1215 at the same dose in in vivo efficacy evaluations of colorectal HCT116, acute myelocytic leukemia MV4-11, and B cell lymphoma Romas xenografts.
Targets |
HDAC6 ( IC50 = 17 nM ); HDAC1 ( IC50 = 422 nM ); HDAC8 ( IC50 = 398 nM )
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ln Vitro |
SKLB-23bb (Compound 23bb) exhibits antiproliferative properties against a panel of cancer cell lines at low nanomolar concentrations. With IC50 values of 50 and 49 nM on A375 and HeLa cells, respectively, SKLB-23bb exhibits the most potent antiproliferative activity against human malignant melanoma A375 cells and cervical cancer HeLa cells. MTT is used to assess the antiproliferative activities of SKLB-23bb against 11 different types of hematological tumors, including myeloma U266 and RPMI8226 cells, human leukemia MV4-11, K562 cells, and human B cell lymphoma Ramos cells, as well as solid tumors, including ovarian cancer A2780s, SKOV-3 cells, breast cancer SKBR3 cells, liver cancer HepG2 cells, lung cancer H460 and A549 cells, cervical cancer HeLa cells, and colon cancer HCT116, HT29 cells. In these tumor cell lines, SKLB-23bb exhibits antiproliferative potential, with IC50 values ranging from 14 to 104 nM[1].
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ln Vivo |
SKLB-23bb (Compound 23bb) decreases the growth of the tumor in the solid tumor HCT116 xenograft model and the hematological tumor MV4-11 xenograft model. SKLB-23bb, administered intravenously at a dose of 50 mg/kg, has been shown to exhibit significant antitumor activities in MV4-11 and HCT116 xenograft models. After intravenous administration of SKLB-23bb at 50 mg/kg, the growth of MV4-11 and HCT116 cancer cell xenografts is suppressed by 55.0% and 76.3% (percent of tumor mass change [TGI] values), respectively. Additionally, the HCT116 xenograft model is set up to study the antitumor effect of SKLB-23bb taken orally. On the HCT116 xenograft model, the oral administration of SKLB-23bb (25 mg/kg) produced a TGI value of 60.4%, which was higher than that of the SAHA group (100 mg/kg, 59.2%). Furthermore, the reduction in body weight is satisfactory, and no additional side effects are noticed while using SKLB-23bb. The results show that SKLB-23bb has a long terminal half-life (t1/2=7.658 h for iv, t1/2=9.62 h for po) and low clearance (CL=7.008 L/kg per hour for iv, CL=12.877 L/kg per hour for po). Rats exhibit good oral bioavailability of SKLB-23bb, with a maximum bioavailability of 47.0%[1].
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Cell Assay |
The following cells are cultured in DMEM: A375, A2780s, SKBR3, HepG2, HeLa, HCT116, A549, and SKOV-3. RPMI-1640 medium is used to cultivate RPMI8226, K562, H460, HT29, and Ramos cells. IMDM is used to cultivate MV4-11 cells. Penicillin 100 units/mL, streptomycin 100 μg/mL, and 10% fetal bovine serum (FBS) are present in all the media. The cells are cultured at 37 °C in a 5% CO2 humidified environment. Logarithmic phase cells are plated at densities of 3000-5000 cells per well in 96-well culture plates. The cells are then treated with different compound concentrations (e.g., SKLB-23bb;10, 100, 1000, and 10000 nM) for 72 hours in final volumes of 200 μL. The cells are incubated for an extra one to three hours after the end point, after which 20 μL of MTT (5 mg/mL) is added to each well. Once the medium has been carefully removed, the precipitates are dissolved using mechanical shaking in 150 μL of DMSO. A spectrophotometer is then used to measure the absorbance at 570 nm. By comparing the percentage of growth to the untreated control, IC50 values are computed[1].
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Animal Protocol |
Mice: In the MV4-11 and Ramos xenograft models, 5- to 6-week-old female NOD/SCID mice have their right flanks subcutaneously injected with 107 MV4-11 and Ramos cells (in 100 μL of serum-free IMDM). In order to create an HCT116 xenograft, 5- to 6-week-old female Balb/c nude mice have their right flanks subcutaneously injected with HCT116 cells (107 cells in 100 μL of serum-free DMEM). The mice are randomly split into control and treated groups when the size of the formed xenografts reaches 100–150 mm3. There are six mice per group in the MV4-11 model, eight mice per group in the Ramos model, and seven mice per group in the HCT116 model. Every two days, the mice in the experimental groups are given SKLB-23bb either orally (25 mg/kg) or intravenously (iv) at a dose of 50 mg/kg. Equal volumes of physiological saline containing 5% ethanol and 5% Cremophor EL are given orally or by intravenous injection to the mice in the vehicle group. Those assigned to the SAHA, LBH-589, or ACY-1215 groups (positive controls) are given an intraperitoneal injection (50 mg/kg for SAHA and 10 mg/kg for LBH-589, dissolved in physiological saline containing 10% DMSO and 45% PEG400 to a concentration of 10 mg/mL) orally every two days (100 mg/kg for SAHA and 40 mg/kg for ACY-1215, dissolved in the same manner as previously described). Every two days, the tumor burden is measured using a caliper. TV, or tumor volume, is computed. Day 0 is the day that the course of treatment began. Mice are sacrificed at the conclusion of the experiment, and tumors are gathered and weighed[1].
Rats: The oral dosage of SKLB-23bb is 12 mg/kg body weight, and the intravenous (IV) dose is 12 mg/kg body weight for SD rats. Using an LC-MS/MS system, blood samples are collected, and the plasma is examined to determine the SKLB-23bb concentration[1]. |
References |
Molecular Formula |
C21H24N4O4
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Molecular Weight |
396.439664840698
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Exact Mass |
396.18
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Elemental Analysis |
C, 63.62; H, 6.10; N, 14.13; O, 16.14
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CAS # |
1815580-06-3
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PubChem CID |
122550211
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Appearance |
White to off-white solid powder
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LogP |
3
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Hydrogen Bond Donor Count |
2
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Hydrogen Bond Acceptor Count |
7
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Rotatable Bond Count |
8
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Heavy Atom Count |
29
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Complexity |
523
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Defined Atom Stereocenter Count |
0
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InChi Key |
FWXZZFONXWYSEF-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C21H24N4O4/c1-14-22-17-8-5-4-7-16(17)21(23-14)25(2)15-10-11-18(28-3)19(13-15)29-12-6-9-20(26)24-27/h4-5,7-8,10-11,13,27H,6,9,12H2,1-3H3,(H,24,26)
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Chemical Name |
N-hydroxy-4-[2-methoxy-5-[methyl-(2-methylquinazolin-4-yl)amino]phenoxy]butanamide
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Synonyms |
HDAC6-IN-1; SKLB-23bb; 23bb; SKLB 23bb
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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: 32~79 mg/mL (80.7~199.3 mM)
Ethanol: ~79 mg/mL |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.31 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 (6.31 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 (6.31 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.5224 mL | 12.6122 mL | 25.2245 mL | |
5 mM | 0.5045 mL | 2.5224 mL | 5.0449 mL | |
10 mM | 0.2522 mL | 1.2612 mL | 2.5224 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.