| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 100mg | |||
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| Targets |
HTH-01-091 targets maternal embryonic leucine zipper kinase (MELK). MELK is a serine/threonine kinase involved in cell cycle regulation, proliferation, and survival. By inhibiting MELK with high potency (IC50 = 10.5 nM), the compound disrupts these processes in cancer cells. It also inhibits several other kinases, including PIM1/2/3, RIPK2, DYRK3, smMLCK, and CLK2. Its activity as a 5-HT6 receptor antagonist suggests potential for neurological applications.
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| ln Vitro |
Over 90% of kinases are specifically inhibited by HTH-01-091 (1 μM) [1]. MELK degradation is caused by cell-permeable HTH-01-091 (0-10 μM, 1 hour) [1]. On breast cancer cells, HTH-01-091 (0–10 μM, 3 days) shows modest anti-proliferative effects [1].
In vitro, HTH-01-091 is a potent MELK inhibitor. It inhibits the growth of cancer cell lines. Its effects on cell proliferation, cell cycle, and apoptosis can be studied in various cancer cell lines. The compound's activity against PIM and other kinases may contribute to its overall antiproliferative effects. It is a valuable tool for studying the role of MELK in cancer and other diseases. |
| ln Vivo |
In vivo, HTH-01-091 can be used for breast cancer research. It is under investigation for its potential use in treating psychiatric and neurological disorders. Its ability to inhibit MELK and other kinases makes it a promising candidate for therapeutic development. Further studies are needed to evaluate its efficacy and safety in animal models of cancer and neurological diseases.
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| Enzyme Assay |
The in vitro kinase assay for HTH-01-091 involves measuring MELK kinase activity. Recombinant MELK is incubated with varying concentrations of HTH-01-091 (0.01-1000 nM) and a peptide substrate. The incorporation of phosphate is measured using a scintillation proximity assay or a fluorescence-based method. IC50 values are calculated. Selectivity is assessed by testing against a panel of kinases (e.g., PIM1/2/3, RIPK2).
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: MDA-MB-468 Cell Tested Concentrations: 0, 0.1, 1.0 and 10 μM Incubation Duration: 1 hour Experimental Results: diminished MELK protein levels in MDA-MB-468 cells; Streptavidin Beads The pull-down effect on MELK was diminished in a dose-dependent manner, indicating that the compound is cell-permeable and binds to MELK in an ATP-competitive manner. There was no effect on ERK1/2 pulldown, indicating that HTH-01-091 has no binding affinity for ERK1/2. Cell proliferation assay[1] Cell Types: MDA-MB-468, BT-549, HCC70, ZR-75-1, MCF7 and T-47D Cell Tested Concentrations: 0, 0.001, 0.01, 0.1, 1.0 and 10 μM Incubation Duration: 3-day Experimental Results: Demonstrated antiproliferative activity in a panel of breast cancer cell lines, including MDA-MB-468, BT-549, HCC70, ZR-75-1, MCF7, and T-47D cells, with IC50 values of 4.00, respectively. μM, 6.16 μM, 8.80 μM, >10 μM, 8.75 μM and 3.87 μM. In vitro cellular assays for HTH-01-091 use cancer cell lines, such as breast cancer cells. Cells are treated with the compound at concentrations of 0.1-1000 nM for 24-72 hours. Cell viability is assessed using MTT or CCK-8 assays. Cell cycle analysis is performed by flow cytometry. Apoptosis is evaluated using caspase-3/7 activity assays and Annexin V staining. MELK and downstream signaling targets are measured by Western blot. |
| Animal Protocol |
In vivo animal studies for HTH-01-091 involve mouse xenograft models using breast cancer cell lines. Tumor-bearing mice are treated with the compound via oral gavage or intraperitoneal injection at doses of 1-50 mg/kg. Tumor volume is measured regularly. The compound's effect on tumor growth is assessed. Pharmacodynamic studies measure MELK inhibition and downstream signaling in tumor tissues.
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| ADME/Pharmacokinetics |
HTH-01-091 has a molecular weight of 499.43 and a molecular formula of C26H28Cl2N4O2. It is a potent MELK inhibitor with an IC50 of 10.5 nM. It is used for breast cancer research. The compound is a research tool and is not for human therapeutic use.
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| References |
| Molecular Formula |
C26H28CL2N4O2
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| Molecular Weight |
499.432124137878
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| Exact Mass |
498.158
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| CAS # |
2000209-42-5
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| PubChem CID |
131801426
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| Appearance |
White to light yellow solid powder
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| LogP |
5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
34
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| Complexity |
707
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C(=C(C=C(C=1)C1C=CC2=C(C=1)C1=C(C=N2)CNC(N1C1CCC(CN(C)C)CC1)=O)Cl)O
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| InChi Key |
FUVRHGKKWNNBJX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H28Cl2N4O2/c1-31(2)14-15-3-6-19(7-4-15)32-24-18(13-30-26(32)34)12-29-23-8-5-16(9-20(23)24)17-10-21(27)25(33)22(28)11-17/h5,8-12,15,19,33H,3-4,6-7,13-14H2,1-2H3,(H,30,34)
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| Chemical Name |
9-(3,5-dichloro-4-hydroxyphenyl)-1-[4-[(dimethylamino)methyl]cyclohexyl]-3,4-dihydropyrimido[5,4-c]quinolin-2-one
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| Synonyms |
HTH01-091 HTH 01-091 HTH-01-091
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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 | 2.0023 mL | 10.0114 mL | 20.0228 mL | |
| 5 mM | 0.4005 mL | 2.0023 mL | 4.0046 mL | |
| 10 mM | 0.2002 mL | 1.0011 mL | 2.0023 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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