QL-X-138 is a potent and specific BTK/MNK dual kinase inhibitor that displays covalent binding to BTK and non-covalent binding to MNK. The IC50s of QL-X-138 against BTK, MNK1 and MNK2 kinases are 9.4 nM, 107.4 nM and 26 nM respectively. QL-X-138 also showed activity against dengue virus 2 with IC50 of 3.5 μM. QL-X-138 may be utilized in the study of B cell malignancies.

Physicochemical Properties

Molecular Formula	C25H19N5O2
Molecular Weight	421.450664758682
Exact Mass	421.153
CAS #	1469988-63-3
PubChem CID	73707530
Appearance	White to off-white solid powder
LogP	3.4
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	32
Complexity	769
Defined Atom Stereocenter Count	0
SMILES	O=C1C=CC2=CN=C3C=CC(C4C=NNC=4)=CC3=C2N1C1C=CC(C)=C(C=1)NC(C=C)=O
InChi Key	JMVDIGHUQAXWIE-UHFFFAOYSA-N
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)
Chemical Name	N-[2-methyl-5-[2-oxo-9-(1H-pyrazol-4-yl)benzo[h][1,6]naphthyridin-1-yl]phenyl]prop-2-enamide
HS Tariff Code	2934.99.9001
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)

Biological Activity

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]
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.
References	[1]. Discovery of a BTK/MNK dual inhibitor for lymphoma and leukemia. Leukemia. 2016 Jan;30(1):173-81. [2]. Discovery of host-targeted covalent inhibitors of dengue virus. Antiviral Res. 2017 Mar;139:171-179.
Additional Infomation	N-[2-methyl-5-[2-oxo-9-(1H-pyrazol-4-yl)-1-benzo[h][1,6]naphthyridinyl]phenyl]-2-propenamide is a naphthyridine derivative.

Solubility Data

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

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (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.