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Purity: ≥98%
| Targets |
JNJ-47117096 HCl targets maternal embryonic leucine zipper kinase (MELK), a serine/threonine kinase that plays important roles in cell cycle regulation, stem cell self-renewal, and cancer progression. MELK is overexpressed in various cancers and has been implicated in promoting tumor growth, proliferation, and resistance to therapy. JNJ-47117096 HCl is a selective MELK inhibitor with an IC50 of 23 nM. The compound also effectively blocks Flt3 (IC50 = 18 nM), a receptor tyrosine kinase involved in hematopoiesis and leukemia. JNJ-47117096 HCl inhibits other kinases including CAMKIIδ (810 nM), Mnk2 (760 nM), CAMKIIγ (1000 nM), and MLCK (1000 nM). The compound was identified through fragment-based drug design.
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| ln Vitro |
JNJ-47117096 hydrochloride has an IC50 of 23 nM, making it a strong and selective MELK inhibitor. Additionally, it blocks Flt3 effectively (IC50 = 18 nM), and it blocks CAMKIIδ, Mnk2, CAMKIIγ, and MLCK (IC50 = 810 nM, 760 nM, 1000 nm, 1000 nm). In the absence of IL-3, JNJ-47117096 (MELK-T1) suppresses Flt3-driven proliferation of the Ba/F3 cell line with an IC50 of 1.5 μM; in the presence of IL-3, no inhibitory effect was detected. Regardless of the presence or absence of IL-3, JNJ-47117096 did not impede the growth of Ba/F3 cell lines transfected with FGFR1, FGFR3, or KDR [1]. MCF-7 cells' entry into the S phase can be postponed by JNJ-47117096 (MELK-T1, 10 μM). MELK is inhibited by JNJ-47117096, leading to replication fork stalling and DNA double-strand breaks (DSBs). The ATM-mediated DNA damage response is activated by JNJ-47117096 (DDR). Growth arrest and senescence characteristics are brought on by JNJ-47117096 (3, 10 μM). Furthermore, JNJ-47117096 causes long-term overexpression of p21, significant phosphorylation of p53, and downregulation of FOXM1 target genes [2].
JNJ-47117096 HCl demonstrates potent in vitro activity against MELK with an IC50 of 23 nM. The compound effectively blocks Flt3 with an IC50 of 18 nM. It also inhibits CAMKIIδ, Mnk2, CAMKIIγ, and MLCK with IC50 values of 810 nM, 760 nM, 1000 nM, and 1000 nM, respectively. The compound's selectivity for MELK and Flt3 over other kinases makes it a valuable tool for studying the roles of these kinases in cancer and hematopoiesis. JNJ-47117096 HCl has been characterized in various in vitro systems, confirming its mechanism of action as a MELK and Flt3 inhibitor. |
| ln Vivo |
In vivo efficacy data for JNJ-47117096 HCl are not extensively documented in publicly available sources. Based on its potent inhibition of MELK and Flt3, the compound is expected to have potential utility in cancer models, particularly those involving MELK-overexpressing tumors or Flt3-driven leukemias. MELK is a well-validated target for cancer therapy, and Flt3 is a key target in acute myeloid leukemia (AML). JNJ-47117096 HCl's activity against both targets may offer advantages for treating cancers that depend on these kinases. Further in vivo studies are needed to fully characterize the compound's therapeutic potential, including its efficacy in disease models, pharmacokinetic properties, and safety profile.
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| Enzyme Assay |
The in vitro enzyme inhibition assay for JNJ-47117096 HCl measures the inhibition of MELK and Flt3 kinase activities. Recombinant human MELK or Flt3 enzymes are incubated with varying concentrations of JNJ-47117096 HCl (typically ranging from nanomolar to micromolar) in the presence of ATP and a peptide substrate. The kinase reaction is allowed to proceed for a fixed period, and the extent of substrate phosphorylation is quantified using techniques such as fluorescence polarization, luminescence-based kinase assays, or radiometric measurement. IC50 values are determined by fitting dose-response curves to the inhibition data (23 nM for MELK, 18 nM for Flt3). The compound is dissolved in DMSO and diluted in assay buffer to achieve the desired final concentrations. Selectivity is assessed by testing the compound against a panel of kinases, including CAMKIIδ, Mnk2, CAMKIIγ, and MLCK. Appropriate positive controls and negative controls are included in each assay run.
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| Cell Assay |
The in vitro cellular assay for JNJ-47117096 HCl is performed using cancer cell lines that depend on MELK or Flt3 for proliferation, such as leukemia cell lines (for Flt3) or solid tumor cell lines with MELK overexpression. Cells are cultured in appropriate medium and treated with varying concentrations of JNJ-47117096 HCl or vehicle control (DMSO) for specified time points. Cell viability and proliferation are assessed using assays such as MTT, CellTiter-Glo, or by direct cell counting. The phosphorylation status of MELK downstream targets and Flt3 signaling proteins (e.g., STAT5, ERK) is assessed by Western blotting using phospho-specific antibodies. The compound's effects on cell cycle progression and apoptosis are evaluated by flow cytometry. Dose-response relationships are established by analyzing cell viability and signaling inhibition across different compound concentrations.
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| Animal Protocol |
In vivo animal experiments with JNJ-47117096 HCl are not extensively described in publicly available sources. Based on its in vitro activity, potential in vivo studies would likely use immunocompromised mice bearing human cancer xenografts or leukemia models. Tumor cells would be implanted subcutaneously or intravenously into mice. When tumors reach a predetermined size or when leukemia is established, animals would be randomized into treatment groups receiving JNJ-47117096 HCl or vehicle control. The compound would be administered via oral gavage or intraperitoneal injection at various doses. Tumor volume or leukemia burden would be measured periodically. At study endpoint, tissues would be harvested for analysis of MELK and Flt3 target engagement, downstream signaling, and markers of proliferation and apoptosis. The compound's antitumor efficacy would be evaluated by comparing disease progression in treated versus control groups.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) parameters for JNJ-47117096 HCl are not extensively documented in publicly available sources. The compound has a molecular weight of 398.88 and a chemical formula of C21H23ClN4O2. The compound is soluble in DMSO for formulation purposes. For in vivo administration, the compound would need to be formulated using appropriate vehicles to ensure adequate solubility and stability. The compound should be stored under conditions recommended by the manufacturer to maintain stability and prevent degradation. Detailed PK parameters including half-life, clearance, volume of distribution, and maximum concentration (Cmax) are not available from the current search results and would require consultation of the primary literature.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for JNJ-47117096 HCl are not extensively documented in publicly available sources. As a research-grade compound, JNJ-47117096 HCl is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. The compound should be stored according to the manufacturer's recommendations to maintain stability and prevent degradation. Comprehensive toxicological profiling (e.g., LD50, maximum tolerated dose, organ-specific toxicity) is not available from the current search results and would require consultation of the primary literature or safety data sheets.
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| References |
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| Additional Infomation |
JNJ-47117096 HCl is a research compound developed for studying the roles of MELK and Flt3 in cancer and hematopoiesis. The compound is also known as MELK-T1. JNJ-47117096 HCl was identified through fragment-based drug design and is a potent, selective MELK inhibitor (IC50 = 23 nM) that also effectively blocks Flt3 (IC50 = 18 nM). The compound also inhibits CAMKIIδ, Mnk2, CAMKIIγ, and MLCK with lower potency. JNJ-47117096 HCl is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical cancer research. JNJ-47117096 HCl is available from various chemical suppliers for research purposes. Its utility lies in its ability to inhibit MELK and Flt3, enabling studies of their roles in cancer and hematopoiesis.
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| Molecular Formula |
C21H23CLN4O2
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| Molecular Weight |
398.885923624039
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| Exact Mass |
398.15
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| CAS # |
1610536-69-0
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| Related CAS # |
1610536-69-0 (HCl);1610586-62-3;
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| PubChem CID |
132472238
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
503
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=C(C=CC(=C1)C2=CNN=C2)C(=O)NC3=CC4=C(CCNCC4)C=C3.Cl
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| InChi Key |
OXRWZUUCCUDKJJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H22N4O2.ClH/c1-27-20-11-15(17-12-23-24-13-17)3-5-19(20)21(26)25-18-4-2-14-6-8-22-9-7-16(14)10-18;/h2-5,10-13,22H,6-9H2,1H3,(H,23,24)(H,25,26);1H
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| Chemical Name |
2-methoxy-4-(1H-pyrazol-4-yl)-N-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)benzamide;hydrochloride
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| Synonyms |
JNJ-47117096 hydrochloride; JNJ 47117096 hydrochloride; JNJ47117096 hydrochloride; JNJ-47117096; JNJ-47117096 HCl; MELK T1; MELK-T1 HCl; MELK-T1
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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) |
DMSO : ≥ 250 mg/mL (~626.74 mM)
H2O : ~3.33 mg/mL (~8.35 mM) |
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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 | 2.5070 mL | 12.5348 mL | 25.0696 mL | |
| 5 mM | 0.5014 mL | 2.5070 mL | 5.0139 mL | |
| 10 mM | 0.2507 mL | 1.2535 mL | 2.5070 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.
 Inhibition of MELK by MELK-T1 (JNJ-47117096).Biosci Rep.2015 Oct 2;35(6). pii: e00267. |
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 MELK-T1 triggers the proteasome-mediated degradation of MELK protein.
MELK-T1 induces a delay in the progression of MCF-7 cells through S-phase.Biosci Rep.2015 Oct 2;35(6). pii: e00267. |
 Effects of MELK-T1 on DNA structure and replication.
Model of how MELK increases the DDT barrier.Biosci Rep.2015 Oct 2;35(6). pii: e00267. |
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