ZM 39923 HCl, the hydrochloride salt of ZM-39923, is a novel and potent inhibitor of Janus kinase-JAK1/3 with potential anti-inflammatory activity. It inhibits JAK1/3 with pIC50s of 4.4/7.1, and shows little/no activity against JAK2 and modestly potency to EGFR; also found to be sensitive to transglutaminase.

Physicochemical Properties

Molecular Formula	C23H25NO.HCL
Molecular Weight	367.91
Exact Mass	367.17
CAS #	1021868-92-7
Related CAS #	ZM39923;273727-89-2
PubChem CID	176406
Appearance	White to off-white solid powder
LogP	6.955
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	7
Heavy Atom Count	26
Complexity	412
Defined Atom Stereocenter Count	0
InChi Key	NJTUORMLOPXPBY-UHFFFAOYSA-N
InChi Code	InChI=1S/C23H25NO.ClH/c1-18(2)24(17-19-8-4-3-5-9-19)15-14-23(25)22-13-12-20-10-6-7-11-21(20)16-22;/h3-13,16,18H,14-15,17H2,1-2H3;1H
Chemical Name	3-[benzyl(propan-2-yl)amino]-1-naphthalen-2-ylpropan-1-one;hydrochloride
Synonyms	Synonym:ZM 39923; ZM-39923; ZM39923 HCl;ZM39923;ZM 39923 Hydrochloride;
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 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)

Biological Activity

ln Vitro	ZM39923 hydrochloride has a pIC50 of 7.1, making it a JAK3 inhibitor. ZM39923 (Compound 7) inhibits tyrosine kinases Lck and CDK4 (pIC50 <5.0) and EGF-R and JAK1 (pIC50, 5.6, and 4.4, respectively) with a modest inhibitory effect[1]. ZM39923 acts directly on pure TGM2 to inhibit the Ca2+ activated form of TGM2, and it potently inhibits tissue transglutaminase (TGM2) with an IC50 of 10 nM[2]. ZM39923 inhibits JAK3 phosphorylation brought on by CCL19; this action is comparable to that of an anti-CCR7 antibody. ZM39923 also dramatically reduces PCI-37B cell migration and invasion and prevents the CCL19-induced wound closure rate[3].
ln Vivo
Animal Protocol
References	[1]. Naphthyl ketones: a new class of Janus kinase 3 inhibitors. Bioorg Med Chem Lett. 2000 Mar 20;10(6):575-9. [2]. Identification of chemical inhibitors to human tissue transglutaminase by screening existing drug libraries. Chem Biol. 2008 Sep 22;15(9):969-78. [3]. Jak3 is involved in CCR7-dependent migration and invasion in metastatic squamous cell carcinoma of the head and neck. Oncol Lett. 2017 May;13(5):3191-3197.

Solubility Data

Solubility (In Vitro)

DMSO: 30 mg/mL (81.5 mM) Water:<1 mg/mL Ethanol:8 mg/mL (21.7 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.80 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.80 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7181 mL	13.5903 mL	27.1806 mL
	5 mM	0.5436 mL	2.7181 mL	5.4361 mL
	10 mM	0.2718 mL	1.3590 mL	2.7181 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.