Cevidoplenib (SKI-O-703) is an orally bioactive spleen tyrosine kinase (Syk) inhibitor (antagonist) with potential anti~inflammatory and Immune-modulatory effects. Cevidoplenib is also the mesylate form of SKI-O-592. Cevidoplenib and SKI-O-592 inhibit BCR-mediated B cell survival, proliferation, and differentiation. SKI-O-592 also potently inhibits multiple kinase activities, with IC50s of 6.2 nM (Syk), 1.859 μM (Jak2), 5.807 μM (Jak3), 0.412 μM (RET), 0.687 μM (KOR), and 1.783 respectively. μM (FLT3), 16.96 μM (FGFR1), 5.662 μM (FGFR3) and 0.709 μM (Pyk2).

Physicochemical Properties

Molecular Formula	C25H27N7O3
Molecular Weight	473.526984453201
Exact Mass	473.217
CAS #	1703788-21-9
Related CAS #	Cevidoplenib dimesylate;2043659-93-2
PubChem CID	91754477
Appearance	Off-white to gray solid powder
Density	1.5±0.1 g/cm3
Boiling Point	751.1±70.0 °C at 760 mmHg
Flash Point	408.0±35.7 °C
Vapour Pressure	0.0±2.6 mmHg at 25°C
Index of Refraction	1.761
LogP	-0.12
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	7
Heavy Atom Count	35
Complexity	769
Defined Atom Stereocenter Count	1
SMILES	CC1=NN(C=C1CN2C[C@@H](CO2)O)C3=NC(=NC=C3)NC4=CC5=C(C=C4)N(C=C5C(=O)C6CC6)C
InChi Key	YCZUBLQESBVOSH-IBGZPJMESA-N
InChi Code	InChI=1S/C25H27N7O3/c1-15-17(10-31-12-19(33)14-35-31)11-32(29-15)23-7-8-26-25(28-23)27-18-5-6-22-20(9-18)21(13-30(22)2)24(34)16-3-4-16/h5-9,11,13,16,19,33H,3-4,10,12,14H2,1-2H3,(H,26,27,28)/t19-/m0/s1
Chemical Name	cyclopropyl-[5-[[4-[4-[[(4S)-4-hydroxy-1,2-oxazolidin-2-yl]methyl]-3-methylpyrazol-1-yl]pyrimidin-2-yl]amino]-1-methylindol-3-yl]methanone
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 Vivo	Following oral treatment, cevidoplenib binds to SYK and inhibits its activity, preventing inflammatory cells such as mast cells, neutrophils, macrophages, and natural killer cells from signaling through the Fc and B-cell receptors (BCR). (NK) and B lymphocytes. 2].
References	[1]. A novel selective spleen tyrosine kinase inhibitor SKI-O-703 (cevidoplenib) ameliorates lupus nephritis and serum-induced arthritis in murine models. Clin Exp Immunol. 2023 Mar 8;211(1):31-45. [2]. International Nonproprietary Names for Pharmaceutical Substances (INN). WHO Drug Information, Vol. 31, No. 4, 2017. [3]. cevidoplenib dimesylate.
Additional Infomation	Cevidoplenib is an orally available inhibitor of spleen tyrosine kinase (SYK), with potential anti-inflammatory and immunomodulating activities. Upon oral administration, cevidoplenib binds to and inhibits the activity of SYK, blocking Fc receptor and B-cell receptor (BCR)-mediated signaling in inflammatory cells, including macrophages, neutrophils, mast cells, natural killer (NK) cells and B-cells. This leads to the inhibition of the activation of these inflammatory cells, and the related inflammatory responses and tissue damage. SYK, a non-receptor cytoplasmic protein tyrosine kinase widely expressed in hematopoietic cells, plays a key role in Fc receptor and B-cell receptor signaling in inflammatory cells. It is involved in coupling activated immunoreceptors, such as Fc receptors and B-cell receptors, to signal downstream events that mediate diverse cellular responses, including proliferation, differentiation, and phagocytosis, which are important for allergic and antibody-mediated immune diseases such as immune thrombocytopenia (ITP).

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~105.59 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.28 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 (5.28 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1118 mL	10.5590 mL	21.1180 mL
	5 mM	0.4224 mL	2.1118 mL	4.2236 mL
	10 mM	0.2112 mL	1.0559 mL	2.1118 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.