QL-47 (also known as QL-XII-47) is a novel, potent, selective and irreversible BTK kinase inhibitor with IC50 of 7 nM. QL47 acts by covalently modifying Cys481 of BTK. QL47 has an IC50 of 7 nM for BTK kinase activity inhibition, an EC50 of 475 nM for autophosphorylation of BTK on Tyr223 in cells, and an EC50 of 318 nM for phosphorylation of a downstream effector PLCγ2 (Tyr759). QL47 causes a G1 cell cycle arrest in Ramos cells, which is linked to a marked BTK protein degradation. At submicromolar concentrations, QL47 prevents B-cell lymphoma cancer cell lines from proliferating.

Physicochemical Properties

Molecular Formula	C27H21N5O2
Molecular Weight	447.487945318222
Exact Mass	447.169
Elemental Analysis	C, 72.47; H, 4.73; N, 15.65; O, 7.15
CAS #	1469988-75-7
Related CAS #	1469988-75-7
PubChem CID	71748056
Appearance	white solid powder
Density	1.4±0.1 g/cm3
Boiling Point	706.2±60.0 °C at 760 mmHg
Flash Point	380.9±32.9 °C
Vapour Pressure	0.0±2.2 mmHg at 25°C
Index of Refraction	1.724
LogP	2.5
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	3
Heavy Atom Count	34
Complexity	860
Defined Atom Stereocenter Count	0
SMILES	O=C1N(C2=C(C=C1)C=NC3=CC=C(C4=CN(C)N=C4)C=C32)C5=CC=C(CC6)C(N6C(C=C)=O)=C5
InChi Key	RTRNJQOBEOISFQ-UHFFFAOYSA-N
InChi Code	InChI=1S/C27H21N5O2/c1-3-25(33)31-11-10-17-4-7-21(13-24(17)31)32-26(34)9-6-19-14-28-23-8-5-18(12-22(23)27(19)32)20-15-29-30(2)16-20/h3-9,12-16H,1,10-11H2,2H3
Chemical Name	9-(1-methylpyrazol-4-yl)-1-(1-prop-2-enoyl-2,3-dihydroindol-6-yl)benzo[h][1,6]naphthyridin-2-one
Synonyms	QL47; QL 47; QL47; QL-XII 47; QL-XII-47; QL XII-47
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	QL47 blocks the initiation of both canonical cap-driven and noncanonical initiation strategies for protein neosynthesis, most likely by focusing on an early stage of translation elongation[2]. QL47 has an EC50 of 475 nM on autophosphorylation of BTK on Tyr223 and an EC50 of 318 nM on phosphorylation of a downstream effector, PLCγ2 (Tyr759). QL47 causes a G1 cell cycle arrest in Ramos cells, which is linked to a marked BTK protein degradation. At submicromolar concentrations, QL47 prevents B-cell lymphoma cancer cell lines from proliferating[3].
References	[1]. Structure-Activity Relationship Study of QL47: A Broad-Spectrum Antiviral Agent. ACS Med Chem Lett. 2017;8(3):344-349. Published 2017 Feb 3. [2]. A broad-spectrum antiviral molecule, QL47, selectively inhibits eukaryotic translation. J Biol Chem. 2020;295(6):1694-1703. [3]. Discovery of a potent, covalent BTK inhibitor for B-cell lymphoma. ACS Chem Biol. 2014;9(5):1086-1091.
Additional Infomation	9-(1-methyl-4-pyrazolyl)-1-[1-(1-oxoprop-2-enyl)-2,3-dihydroindol-6-yl]-2-benzo[h][1,6]naphthyridinone is a naphthyridine derivative.

Solubility Data

Solubility (In Vitro)

DMSO: ~1 mg/mL (~2.2 mM)

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	2.2347 mL	11.1734 mL	22.3469 mL
	5 mM	0.4469 mL	2.2347 mL	4.4694 mL
	10 mM	0.2235 mL	1.1173 mL	2.2347 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.