S-Ruxolitinib, the S-enantiomer of ruxolitinib which is also known as INC424 and INCB18424 or INCB018424, is the first-in class, potent, selective, and orally bioavailable JAK1/2 (Janus-associated kinase) inhibitor with IC50 of 3.3 nM/2.8 nM in cell-free assays, it exhibits >130-fold selectivity for JAK1/2 versus JAK3. Ruxolitinib has potential antineoplastic and immunomodulating activities. It was approved in 2011 by FDA for the treatment of intermediate or high-risk myelofibrosis, a type of myeloproliferative disorder that affects the bone marrow, and for polycythemia vera (PCV) when there has been an inadequate response to or intolerance of hydroxyurea. It selectively binds to and inhibits protein tyrosine kinases JAK 1 and 2, which may lead to a reduction in inflammation and an inhibition of cellular proliferation.

Physicochemical Properties

Molecular Formula	C17H18N6
Molecular Weight	306.365022182465
Exact Mass	306.159
Elemental Analysis	C, 66.65; H, 5.92; N, 27.43
CAS #	941685-37-6
Related CAS #	Ruxolitinib;941678-49-5;Ruxolitinib phosphate;1092939-17-7;(Rac)-Ruxolitinib-d9;2469553-67-9;Ruxolitinib sulfate;1092939-16-6
PubChem CID	50878566
Appearance	Typically exists as white to off-white solids at room temperature
Density	1.4±0.1 g/cm3
Boiling Point	592.6±50.0 °C at 760 mmHg
Flash Point	312.2±30.1 °C
Vapour Pressure	0.0±1.7 mmHg at 25°C
Index of Refraction	1.747
LogP	1.69
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	23
Complexity	453
Defined Atom Stereocenter Count	1
SMILES	[C@H](C1CCCC1)(N1N=CC(C2N=CN=C3NC=CC=23)=C1)CC#N
InChi Key	HFNKQEVNSGCOJV-HNNXBMFYSA-N
InChi Code	InChI=1S/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-/m0/s1
Chemical Name	(3S)-3-Cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propanenitrile
Synonyms	S Ruxolitinib; INCB-018424, INCB 018424, INCB018424; INC424, INC424, INC-424; INCB18424, INCB 18424, INCB-18424; Jakafi and Jakavi (trade name); (S)-INCB018424; S-Ruxolitinib; SRuxolitinib;
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

Targets	JAK
ln Vitro	The S enantiomer of rufolitinib (S-Ruxolitinib; 10μM; 12 hours) suppresses the production of ISG, IFIT, and IFITM that is stimulated by IFNβ [1].
ln Vivo	Ruxolitinib (S enantiomer) (S-Ruxolitinib; oral gavage; 30 mg/kg; twice daily, 10–12 hours apart, for 8 weeks) inhibits the growth of hematopoietic cells in MPN [2].
Cell Assay	RT-PCR[1] Cell Types: Human small airway epithelial cells (SAECs) Tested Concentrations: 10 μM Incubation Duration: 12 hrs (hours) Experimental Results: Suppressed IFNβ-induced expression of ISG, IFIT, and IFITM.
Animal Protocol	Animal/Disease Models: Female wild-type C57BL/6J or Nes-gfp27 mice with myeloproliferative neoplasms (MPNs) in peripheral blood[2] Doses: 30 mg/kg (in 0.5% hydroxypropylmethylcellulose after solubilisation in DMSO) Route of Administration: po (oral gavage); twice per day separated 10-12 h for 8 weeks Experimental Results: decreased haematopoietic cell expansion in MPN but it did not rescue bone marrow (BM) mesenchymal stem cells (MSCs).
References	[1]. JAK inhibitors dampen activation of interferon-stimulated transcription of ACE2 isoforms in human airway epithelial cells. Commun Biol. 2021 Jun 2;4(1):654. [2]. Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms. Nature. 2014 Aug 7;512(7512):78-81.
Additional Infomation	See also: Ruxolitinib (annotation moved to).

Solubility Data

Solubility (In Vitro)

DMSO: 61 mg/mL (199.1 mM) Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.16 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 (8.16 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 (8.16 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. Solubility in Formulation 4: 0.5% CMC+0.25% Tween 80:30mg/mL  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.2640 mL	16.3201 mL	32.6403 mL
	5 mM	0.6528 mL	3.2640 mL	6.5281 mL
	10 mM	0.3264 mL	1.6320 mL	3.2640 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.