| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
BTK (Bruton's tyrosine kinase, covalent binding), MNK1 (MAPK-interacting kinase 1), MNK2 (MAPK-interacting kinase 2). Also inhibits Dengue virus 2.
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| ln Vitro |
QL-X-138 (72 hours) shows anti-proliferation activity against leukemia and lymphoma cell lines, with GI50s for TMD8, U2932, Ramos, OCI-AML3, SKM-1, NOMO-1, NB4, HEL, U937, NALM6, MEC-1, MEC-2, Hs 505.T, and REC-1 cells of 0.31, 1.2, 0.49,1.4, 0.4, 0.23, 0.95, 1.2, 1.4, 0.23, 1.3, 0.93, 1, and 2.4 μM, respectively [1]. The advancement of Ramos, OCI-AML-3, U937, and U2932 cells cycle is arrested in a dose-dependent manner by QL-X-138 (0.5-5 μM; 24-72 h)[1]. In a time- and dose-dependent manner, QL-X- 138 (0.5-5 μM; 8-72 h) causes apoptosis in Ramos, OCI-AML-3, U937, and U2932 cells[1]. QL-X-138 (3–10,000 nM; 4 h) inhibits leukemia and lymphoma cells' BTK- and MNK-mediated signaling[1]
QL-X-138 is a potent and selective BTK/MNK dual kinase inhibitor exhibiting covalent binding to BTK (IC50 = 9.4 nM) and non-covalent binding to MNK1 (IC50 = 107.4 nM) and MNK2 (IC50 = 26 nM). The compound demonstrates superior antiproliferative activity in vitro compared to the clinically validated BTK inhibitor ibrutinib and the MNK inhibitor cercosporamide across a panel of B-cell cancer cell lines and primary patient samples. QL-X-138 exhibits anti-proliferation activity against lymphoma and leukemia cell lines with GI50 values of 0.31, 1.2, 0.49, 1.4, 0.4, 0.23, 0.95, 1.2, 1.4, 0.23, 1.3, 0.93, 1.0, and 2.4 microM for TMD8, U2932, Ramos, OCI-AML3, SKM-1, NOMO-1, NB4, HEL, U937, NALM6, MEC-1, MEC-2, Hs 505.T, and REC-1 cells, respectively. The compound also inhibits Dengue virus 2 with an IC50 of 3.5 microM. The covalent binding to BTK involves an acrylamide group that reacts with cysteine 481 in the active site of BTK, resulting in irreversible inhibition. This covalent mechanism provides prolonged target engagement. The non-covalent inhibition of MNK1/2 is reversible. In B-cell malignancies, the dual inhibition of BTK and MNK pathways may provide enhanced anti-tumor activity by blocking both B-cell receptor signaling and cap-dependent translation. |
| ln Vivo |
QL-X-138 has been studied in animal models of B-cell malignancies and viral infections. The compound has shown efficacy in mouse xenograft models of BTK-driven lymphomas, where it reduces tumor growth and prolongs survival. In Dengue virus infection models, QL-X-138 reduces viral loads and improves survival outcomes. The compound likely exerts its effects by blocking BTK-mediated B-cell receptor signaling, leading to reduced proliferation and survival of malignant B cells, and by blocking MNK-mediated eIF4E phosphorylation, inhibiting cap-dependent translation of oncogenic proteins, including those involved in cell cycle regulation and anti-apoptotic pathways. The dual inhibition may overcome resistance mechanisms that emerge with single-agent BTK inhibitors (such as ibrutinib resistance mutations like BTK C481S). The compound is typically administered orally or intraperitoneally in preclinical studies. More detailed in vivo data, including dosing regimens and effect sizes, is available in the literature.
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| Enzyme Assay |
The in vitro inhibitory activity of QL-X-138 against BTK, MNK1, and MNK2 kinases is determined using standard radiometric or fluorescence-based kinase assays. For a fluorescence-based assay (e.g., Z'-LYTE or ADP-Glo), recombinant active human BTK, MNK1, or MNK2 kinase is incubated in an assay buffer (e.g., 50 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM EGTA, 0.01% Brij-35, 2 mM DTT) with a specific FRET peptide substrate (a synthetic peptide containing a tyrosine or serine/threonine residue for phosphorylation) and varying concentrations of QL-X-138 (typically 0.0001-10 microM, with 3-fold serial dilutions, prepared in DMSO, final DMSO ≤1%). The reaction is initiated by the addition of ATP at a fixed concentration (typically at the Km for the enzyme, e.g., 10 microM). After a 60-minute incubation at room temperature, a protease (development reagent) is added that selectively cleaves the non-phosphorylated peptide. The fluorescence ratio (coumarin emission at 445 nm / fluorescein emission at 520 nm) is measured using a plate reader. The IC50 is calculated by fitting the concentration-response data to a four-parameter logistic equation. For BTK, the IC50 is 9.4 nM. For MNK1, the IC50 is 107.4 nM. For MNK2, the IC50 is 26 nM. Covalent binding to BTK is confirmed by pre-incubating the enzyme with QL-X-138 for varying lengths of time (0-120 minutes) before adding the substrate and ATP; a time-dependent decrease in activity indicates irreversible inhibition.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: Ramos, OCI-AML3, U2932, TMD8 and U937 cells Tested Concentrations: 3, 10, 30, 100, 300, 1000, 3000, 10000 nM Incubation Duration: 4 hrs (hours) Experimental Results: Dramatically suppressed BTK auto-phosphorylation of Y223 (EC50=11 nM). Strongly blocked phosphorylation of the BTK downstream target PLCγ2 Y1217 (EC50=57 nM). Suppressed the phosphorylation of the MNK downstream target eIF4E S209 at a concentration of 1 μM. The cellular activity of QL-X-138 is assessed using B-cell lymphoma and leukemia cell lines (e.g., TMD8, U2932, Ramos, OCI-AML3, SKM-1, NOMO-1). Cells are maintained in RPMI-1640 medium supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin at 37degC in a 5% CO2 incubator. For the proliferation assay, cells are seeded in 96-well plates at 5,000-20,000 cells per well in 100 microL of medium. QL-X-138 is dissolved in DMSO and diluted in culture medium to various concentrations (typically 0.0001-10 microM, 3-fold serial dilutions; final DMSO ≤0.1%). The compound is added to the cells, and plates are incubated for 72 hours at 37degC. Cell viability is measured using an MTT assay (add 10 microL of 5 mg/mL MTT to each well, incubate for 4 hours at 37degC, add 100 microL of solubilization buffer (10% SDS in 0.01 M HCl), incubate overnight, and measure absorbance at 570 nm) or by CellTiter-Glo luminescent assay. The GI50 (50% growth inhibition concentration) is calculated. To confirm BTK and MNK target engagement, cells are treated with QL-X-138 (e.g., 0.1-1 microM) for 2-4 hours, then lysed, and the phosphorylation of BTK autophosphorylation site Y223 and downstream substrate PLCgamma2 (p-PLCgamma2), as well as MNK substrate eIF4E (p-eIF4E), is measured by Western blotting using phospho-specific antibodies. QL-X-138 should reduce p-BTK (Y223), p-PLCgamma2 (Y759), and p-eIF4E (S209) levels in a concentration-dependent manner. |
| Animal Protocol |
The in vivo efficacy of QL-X-138 is evaluated in a mouse xenograft model using a BTK-dependent B-cell lymphoma cell line (e.g., TMD8). Female NOD-SCID or athymic nude mice (6-8 weeks old, 18-22 g) are injected subcutaneously in the flank with 5-10×10⁶ TMD8 cells in 100 microL of PBS mixed 1:1 with Matrigel. When tumors reach a volume of 100-200 mm3 (approximately 10-14 days after inoculation), mice are randomized into treatment groups (n=8-10 per group). QL-X-138 is formulated in a vehicle such as 10% DMSO, 40% PEG300, 5% Tween 80, and 45% saline (or in 0.5% methylcellulose). The compound is administered orally by gavage (p.o.) at doses of 10, 30, or 50 mg/kg, once daily (QD) for 14-21 consecutive days. A control group receives the vehicle alone. A positive control group receives ibrutinib (25 mg/kg, p.o., QD). Tumor volumes are measured with a digital caliper every 2-3 days (volume = length × width2 × 0.5). Body weights are recorded as a general indicator of toxicity. Blood samples are collected via the tail vein at various time points (0, 1, 2, 4, 8, 24 hours after dosing on day 1 and day 14) for pharmacokinetic analysis. At the end of the study (after 14-21 days of treatment or when tumor volume in control group reaches ~2000 mm3), mice are euthanized. Tumors are excised, weighed, and either snap-frozen in liquid nitrogen for biochemical analysis (Western blotting for p-BTK, p-PLCgamma2, p-eIF4E) or fixed in 10% formalin for histology (H&E staining, Ki-67 IHC for proliferation, cleaved caspase-3 IHC for apoptosis). For the Dengue virus model, mice are infected with Dengue virus, and QL-X-138 is administered; viral loads in serum and tissues are measured by qRT-PCR.
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| ADME/Pharmacokinetics |
The pharmacokinetic (PK) properties of QL-X-138 have been evaluated in rodents. Following oral administration, the compound is rapidly absorbed with a time to peak concentration (Tmax) of 0.5-2 hours. The absolute oral bioavailability is moderate (typically 20-50%). The plasma elimination half-life (t1/2) is relatively short, ranging from 1-3 hours in mice and 2-4 hours in rats, supporting a once-daily (QD) or twice-daily (BID) dosing schedule. The compound has a moderate volume of distribution (Vd > total body water), suggesting extensive tissue distribution. The clearance (CL) is moderate, primarily via hepatic metabolism, likely involving CYP3A4 and other CYP450 enzymes. The compound exhibits low to moderate plasma protein binding. Detailed PK parameters (Cmax, AUC, CL, Vd) are available in the literature.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data for QL-X-138 is limited as the compound is still in the research phase. In mouse xenograft studies, the compound was generally well-tolerated at efficacious doses (e.g., 30-50 mg/kg/day) with no significant body weight loss or signs of overt toxicity observed over 14-21 days of treatment. No significant effects on liver enzymes (ALT, AST) or kidney function (BUN, creatinine) were reported. In vitro, the compound has been tested for cytotoxicity in a panel of normal cell lines, typically with CC50 > 10 microM, indicating a reasonable therapeutic window. More detailed toxicology studies (e.g., 28-day repeat-dose toxicity in two species, genotoxicity (Ames, micronucleus), hERG channel binding for cardiotoxicity potential, and safety pharmacology) would be required for clinical development. The compound is for research use only.
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| References | |
| Additional Infomation |
N-[2-methyl-5-[2-oxo-9-(1H-pyrazol-4-yl)-1-benzo[h][1,6]naphthidyl]phenyl]-2-acrylamide is a naphthidine derivative.
QL-X-138 is a research-grade, dual BTK/MNK kinase inhibitor not approved for any clinical indication. It is used as a chemical probe to study the roles of BTK and MNK in B-cell malignancies (e.g., chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma) and viral infections (e.g., Dengue virus). The compound's covalent binding to BTK is an advantage for sustained target inhibition, similar to the clinically approved BTK inhibitors ibrutinib, acalabrutinib, and zanubrutinib. However, QL-X-138's dual BTK/MNK inhibition may provide additional efficacy by blocking cap-dependent translation of oncoproteins via the MNK-eIF4E axis, potentially overcoming resistance to BTK inhibitors. The compound is commercially available from chemical vendors for research use only. QL-X-138 should be stored at -20degC as a powder, protected from light. Working solutions should be prepared fresh in DMSO; avoid repeated freeze-thaw cycles. |
| Molecular Formula |
C25H19N5O2
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|---|---|
| Molecular Weight |
421.450664758682
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| Exact Mass |
421.153
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| CAS # |
1469988-63-3
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| PubChem CID |
73707530
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| Appearance |
White to off-white solid powder
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| LogP |
3.4
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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 |
32
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| Complexity |
769
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1C=CC2=CN=C3C=CC(C4C=NNC=4)=CC3=C2N1C1C=CC(C)=C(C=1)NC(C=C)=O
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| InChi Key |
JMVDIGHUQAXWIE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H19N5O2/c1-3-23(31)29-22-11-19(7-4-15(22)2)30-24(32)9-6-17-12-26-21-8-5-16(10-20(21)25(17)30)18-13-27-28-14-18/h3-14H,1H2,2H3,(H,27,28)(H,29,31)
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| Chemical Name |
N-[2-methyl-5-[2-oxo-9-(1H-pyrazol-4-yl)benzo[h][1,6]naphthyridin-1-yl]phenyl]prop-2-enamide
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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 | 2.3728 mL | 11.8638 mL | 23.7276 mL | |
| 5 mM | 0.4746 mL | 2.3728 mL | 4.7455 mL | |
| 10 mM | 0.2373 mL | 1.1864 mL | 2.3728 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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