NSC 42834 (also known as NSC42834; JAK2 Inhibitor V) is a novel, potent and specific inhibitor of JAK2 which inhibits JAK2-V617F and JAK2-WT autophosphorylation in a dose-dependent manner with IC50 values between 10 and 30 µM. It was not cytotoxic to cells at concentrations that inhibited kinase activity.
Physicochemical Properties
| Molecular Formula | C23H24N2O |
| Molecular Weight | 344.449465751648 |
| Exact Mass | 344.188 |
| CAS # | 195371-52-9 |
| PubChem CID | 238484 |
| Appearance | Colorless to light yellow ointment |
| Density | 1.1±0.1 g/cm3 |
| Boiling Point | 520.4±50.0 °C at 760 mmHg |
| Flash Point | 263.0±36.5 °C |
| Vapour Pressure | 0.0±1.4 mmHg at 25°C |
| Index of Refraction | 1.586 |
| LogP | 4.06 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 26 |
| Complexity | 408 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C(C1=CC=CC=C1)C(CCC2=NC=CC=C2)(C)CCC3=NC=CC=C3 |
| InChi Key | SETYDCSRABYHSW-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C23H24N2O/c1-23(15-13-20-11-5-7-17-24-20,16-14-21-12-6-8-18-25-21)22(26)19-9-3-2-4-10-19/h2-12,17-18H,13-16H2,1H3 |
| Chemical Name | 2-methyl-1-phenyl-4-(pyridin-2-yl)-2-(2-(pyridin-2-yl)ethyl)butan-1-one |
| Synonyms | NSC 42834; NSC42834; Janus-Associated Kinase Inhibitor V; NSC-42834; Z3. JAK2 Inhibitor V. |
| 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 | Tyk2 and c-Src kinase function are unaffected by NSC 42834 (JAK2 inhibitor V), which specifically suppresses Jak2 kinase activity. The proliferation of the human erythroleukemia cell line HEL 92.1.7, which expresses Jak2-V617F, is greatly inhibited by NSC 42834. Significant cell cycle arrest and lower levels of Jak2 and STAT3 tyrosine phosphorylation were linked to the NSC 42834-mediated reduction in cell proliferation. Lastly, hematopoietic progenitor cells derived from the bone marrow of individuals with polycythemia vera who have the Jak2-F537I mutation and essential thrombocythemia who harbor the Jak2-V617F mutation are inhibited in growth by NSC 42834. |
| References |
[1]. Z3, a novel Jak2 tyrosine kinase small-molecule inhibitor that suppresses Jak2-mediated pathologic cell growth . Mol Cancer Ther 2008;7(8):2308-18. [2]. Jacqueline Sayyah, Peter P. Sayeski. Jak2 inhibitors: Rationale and role as therapeutic agents in hematologic malignancies. Current Oncology Reports. 2009, 11(2): 117-124. [3]. Ehab Atallah , Srdan Verstovsek . Prospect of JAK2 inhibitor therapy in myeloproliferative neoplasms. Expert Review of Anticancer Therapy. 2009,9 (5):663-670. |
Solubility Data
| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~290.32 mM) Ethanol : ~100 mg/mL (~290.32 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.26 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 (7.26 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 (7.26 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 | 2.9032 mL | 14.5159 mL | 29.0318 mL | |
| 5 mM | 0.5806 mL | 2.9032 mL | 5.8064 mL | |
| 10 mM | 0.2903 mL | 1.4516 mL | 2.9032 mL |