Ruxolitinib CAS#941678-49-5
Highly Effective JAK1/JAK2 Inhibitor: Acts as a potent ATP-competitive inhibitor of JAK1 and JAK2, with strong inhibitory activity at nanomolar concentrations.
Broad Therapeutic Application: Approved for the treatment of intermediate- or high-risk myelofibrosis, providing an effective option for patients with this hematological disorder.
High Kinase Selectivity: Demonstrates strong selectivity toward JAK1 and JAK2 while showing limited activity against JAK3 and other kinase targets.
Regulates JAK-STAT Signaling Pathway: Effectively suppresses JAK-STAT pathway activation, helping inhibit myeloproliferation, promote apoptosis, and reduce cytokine levels.
Ruxolitinib CAS#941678-49-5
In November 2011, the U.S. FDA approved Ruxolitinib (INCB018424) for the treatment of patients with intermediate- or high-risk myelofibrosis. Ruxolitinib is an ATP-competitive inhibitor targeting JAK1 and JAK2, with IC50 values of 3.3±1.2 nM and 2.8±1.2 nM, respectively. Its inhibitory activity is independent of JAK2V617F mutation status.
Ruxolitinib also exhibits moderate inhibitory activity against the related kinase TYK2 (IC50=19±3.2 nM), while showing selectivity over JAK3 (IC50=428±243 nM). In addition, it demonstrates high selectivity against a panel of 26 other kinases at concentrations approximately 100 times higher than the IC50 values for JAK1 and JAK2.
By inhibiting JAK1 and JAK2, Ruxolitinib downregulates the JAK-STAT signaling pathway, thereby suppressing myeloproliferation, inducing apoptosis, and reducing the levels of multiple cytokines in plasma.
Ruxolitinib Chemical Properties
| Melting point | 84-89°C |
| density | 1.4 |
| storage temp. | -20° |
| solubility | Soluble in DMSO (up to 28 mg/ml) or in Ethanol (up to 15 mg/ml with warming). |
| form | White powder. |
| pka | 11.63±0.50(Predicted) |
| color | White |
| Stability: | Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months. |
| InChI | InChI=1/C17H18N6/c18-7-5-15(12-3-1-2-4-12)23-10-13(9-22-23)16-14-6-8-19-17(14)21-11-20-16/h6,8-12,15H,1-5H2,(H,19,20,21)/t15-/s3 |
| InChIKey | HFNKQEVNSGCOJV-UJHUVDBMNA-N |
| SMILES | [C@@H](C1CCCC1)(N1N=CC(C2N=CN=C3NC=CC=23)=C1)CC#N |&1:0,r| |
| CAS DataBase Reference | 941678-49-5 |
| HS Code | 29335990 |
| Hazardous Substances Data | 941678-49-5(Hazardous Substances Data) |
Product Application Of Ruxolitinib CAS#941678-49-5
Janus-associated kinases (JAKs) are cytoplasmic tyrosine kinases that play an essential role in mediating the signaling pathways of specific cytokines and growth factor receptors. The JAK2 gene mutation JAK2V617F, which leads to uncontrolled activation of various growth factors and cytokines, has been associated with myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis.
Ruxolitinib is a potent ATP-mimetic inhibitor that targets both JAK1 and JAK2, with IC50 values of 2.7 nM and 4.5 nM, respectively, while exhibiting relatively lower selectivity toward JAK3 (IC50 = 322 nM). It can inhibit interleukin-6 (IL-6) signaling (IC50 = 281 nM) and suppress the proliferation of JAK2V617F-positive Ba/F3 cells (IC50 = 127 nM).
In primary cell cultures, Ruxolitinib selectively inhibits erythroid progenitor colony formation from JAK2V617F-positive polycythemia vera patient samples (IC50 = 67 nM), while showing significantly lower inhibition in healthy donor samples (IC50 > 400 nM). In a mouse model of JAK2V617F-positive myeloproliferative neoplasms, administration of 90 mg/kg Ruxolitinib reduced splenomegaly, lowered circulating IL-6 and TNF-α levels, eliminated abnormal cells, and extended the survival time of treated animals.
