| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
HDAC1, HDAC6, and mTOR. HDACs/mTOR Inhibitor 1 is a dual HDACs and mTOR inhibitor with IC₅0 values of 0.19 nM for HDAC1, 1.8 nM for HDAC6, and 1.2 nM for mTOR. It shows selectivity over PI3Kalpha (IC₅0 >500 nM).
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| ln Vitro |
HDACs/mTOR Inhibitor 1 (Compound 12l) suppresses the growth of the cell cycle; the 50s of MV4-11, OCI-AML2, and OCI-AML3IC are, respectively, 4.05, 9.01, and 9.98 μM [1]. mTOR Inhibitor 1 and HDACs (0-10 μM) HDACs/mTOR Inhibitor 1 (10 to 1000 nM, 48 h) decreases the S phase in MV4-11 cells, and 6 or 24 hours later, it decreases the p-ERK levels in MV4-11 cells while increasing the levels of Ac-H3 [1].
HDACs/mTOR Inhibitor 1 inhibits HDAC1 with an IC₅0 of 0.19 nM, HDAC6 with an IC₅0 of 1.8 nM, and mTOR with an IC₅0 of 1.2 nM. It stimulates cell cycle arrest in G0/G1 phase and induces tumor cell apoptosis. The compound shows low toxicity in vivo and can be used in research of hematologic malignancies. |
| ln Vivo |
In the MV4-11 and MM1S xenograft NOD/SCID tumor models, HDACs/mTOR Inhibitor 1 (Compound 12l) (10 or 20 mg/kg, tail vein injection) did not exhibit any overt toxicity in terms of central tumor growth [1].
In vivo, HDACs/mTOR Inhibitor 1 demonstrates low toxicity and induces tumor cell apoptosis. The dual inhibition of HDACs and mTOR provides synergistic antitumor effects. Efficacy would be assessed in xenograft models of hematologic malignancies. |
| Enzyme Assay |
HDAC enzymatic activity is measured using a fluorogenic peptide substrate assay. Recombinant HDAC1 or HDAC6 is incubated with a peptide substrate containing an acetylated lysine residue and serial dilutions of test compound. Deacetylation generates a fluorescent signal, and IC₅0 values are calculated from dose-response curves. mTOR kinase activity is measured using a kinase assay with recombinant mTOR and a substrate (e.g., 4E-BP1 or S6K). Phosphorylation is detected by fluorescence or luminescence methods. IC₅0 values are calculated from dose-response curves.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: MV4-11 cells Tested Concentrations: 0.01, 0.1, 1, 10 μM Incubation Duration: 6 h or 24 h Experimental Results: p-ERK down-regulated and increased the percentage of G0/G1 phase cells[1]. (24 h) and Ac-H3 (6 h) increased in a dose-dependent manner. Cancer cell lines (e.g., hematologic malignancy cell lines) are treated with HDACs/mTOR Inhibitor 1 at various concentrations. HDAC activity and mTOR signaling (p-S6K, p-4E-BP1) are assessed by Western blotting. Cell cycle analysis is performed by flow cytometry to assess G0/G1 arrest. Apoptosis is measured by caspase-3/7 activation or Annexin V staining. Cell viability is assessed using MTT or CellTiter-Glo assays. |
| Animal Protocol |
Animal/Disease Models: MV4-11 xenograft NOD/SCID mouse model [1]
Doses: 10 mg/kg Route of Administration: intravenous (iv) (iv)injection, every two days (Q2D) × 6 Experimental Results: TGI (tumor growth inhibition rate) was 53.1 %. Mice bearing subcutaneous xenografts of hematologic malignancies are administered HDACs/mTOR Inhibitor 1 via appropriate routes. Tumor growth is monitored by caliper measurements. Tumors are harvested for pharmacodynamic analysis of HDAC inhibition, mTOR pathway inhibition, and apoptosis markers. Efficacy is determined by tumor growth inhibition and survival. |
| ADME/Pharmacokinetics |
HDACs/mTOR Inhibitor 1 has a molecular weight of 566.65 g/mol and formula C2₈H3₈N₈O₅. Standard PK parameters (half-life, Cmax, AUC, clearance, volume of distribution, oral bioavailability) would be determined in rodent studies. The compound is formulated in suitable vehicles (e.g., DMSO) for in vivo administration.
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| Toxicity/Toxicokinetics |
HDACs/mTOR Inhibitor 1 shows low toxicity in vivo. Standard preclinical safety assessment would include cytotoxicity screening, hERG channel inhibition testing, and repeat-dose toxicology studies in rodents. Given the dual HDAC/mTOR inhibition, potential on-target toxicities (e.g., hematologic, gastrointestinal, metabolic effects) would be evaluated.
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| References | |
| Additional Infomation |
HDACs/mTOR Inhibitor 1 is a research compound for studying hematologic malignancies. It is not clinically approved. The compound's dual inhibition of HDACs and mTOR provides a synergistic mechanism for anticancer therapy. It is useful for investigating the role of HDAC and mTOR signaling in cancer and for developing novel combination therapies for hematologic malignancies.
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| Molecular Formula |
C28H38N8O5
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|---|---|
| Molecular Weight |
566.651925563812
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| Exact Mass |
566.296
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| CAS # |
2271413-06-8
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| PubChem CID |
137628684
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| Appearance |
White to off-white solid powder
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| LogP |
1.5
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
41
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| Complexity |
840
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O1CCN(C(NC2C=CC(=CC=2)C2N=C3C(C=NN3CCCCCCC(NO)=O)=C(N=2)N2CCOCC2)=O)C[C@H]1C
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| InChi Key |
YPXRCUVTZDXVHY-HXUWFJFHSA-N
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| InChi Code |
InChI=1S/C28H38N8O5/c1-20-19-35(14-17-41-20)28(38)30-22-9-7-21(8-10-22)25-31-26(34-12-15-40-16-13-34)23-18-29-36(27(23)32-25)11-5-3-2-4-6-24(37)33-39/h7-10,18,20,39H,2-6,11-17,19H2,1H3,(H,30,38)(H,33,37)/t20-/m1/s1
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| Chemical Name |
(2R)-N-[4-[1-[7-(hydroxyamino)-7-oxoheptyl]-4-morpholin-4-ylpyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-2-methylmorpholine-4-carboxamide
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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 : ~32.5 mg/mL (~57.35 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (3.83 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 21.7 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: ≥ 2.17 mg/mL (3.83 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 21.7 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 | 1.7648 mL | 8.8238 mL | 17.6476 mL | |
| 5 mM | 0.3530 mL | 1.7648 mL | 3.5295 mL | |
| 10 mM | 0.1765 mL | 0.8824 mL | 1.7648 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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