Sovilnesib (AMG 650) is an orally bioavailable inhibitor of kinesin-like protein KIF18A with IC50 of 0.071 μM. Sovilnesib may be used in cancer research.

Physicochemical Properties

Molecular Formula	C26H34F2N6O4S
Molecular Weight	564.65
Exact Mass	564.233
CAS #	2410796-79-9
PubChem CID	148163435
Appearance	White to off-white solid powder
LogP	3.8
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	8
Heavy Atom Count	39
Complexity	958
Defined Atom Stereocenter Count	0
SMILES	C(NC1C=C(C)N=C(N2CCC(F)(F)CC2)N=1)(=O)C1=CC=C(NS(CCO)(=O)=O)C=C1N1CCC2(CC2)CC1
InChi Key	KBDGEJDIHZDPHN-UHFFFAOYSA-N
InChi Code	InChI=1S/C26H34F2N6O4S/c1-18-16-22(31-24(29-18)34-12-8-26(27,28)9-13-34)30-23(36)20-3-2-19(32-39(37,38)15-14-35)17-21(20)33-10-6-25(4-5-25)7-11-33/h2-3,16-17,32,35H,4-15H2,1H3,(H,29,30,31,36)
Chemical Name	2-(6-azaspiro[2.5]octan-6-yl)-N-[2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl]-4-(2-hydroxyethylsulfonylamino)benzamide
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	KIF18A[1]
ln Vitro	Sovilnesib (AMG 650; 0-10 pM; 96 and 144 h; tumor cell lines) suppresses the development of tumor cells in a dose-dependent manner and possesses anti-proliferative effects [1].
ln Vivo	Sovilnesib (AMG 650; 10-100 mg/kg; po; daily for 45 days; female athymic nude mouse OVCAR-3 xenograft model) exhibited no obvious toxicity and suppressed the formation of tumors, with 50% of mice showing persistent tumor regression and cure [1].
Cell Assay	Cell Viability Assay[1] Cell Types: Cancer cell lines Tested Concentrations: 0-10 pM Incubation Duration: 96 and 144 hrs (hours) Experimental Results: Inhibited tumor cell growth in a dose-dependent manner.
Animal Protocol	Animal/Disease Models: Female nude mice without thymus with OVCAR-3 xenografts Doses: 10, 30, and 100 mg/kg Route of Administration: Oral administration; daily, for 45 days Experimental Results: Had antitumor efficacy in a dose-dependent manner.
References	[1]. Kif18a inhibitors for treatment of neoplastic diseases. WO2021211549. [2]. Kif18a inhibitors. WO2020132648.
Additional Infomation	Sovilnesib is an orally bioavailable, small-molecule inhibitor of the human kinesin-like protein KIF18A, with potential antineoplastic activity. Upon oral administration, sovilnesib selectively inhibits the activity of KIF18A. This may result in multipolar cell division and inhibit tumor cell proliferation. KIF18A, a mitotic kinesin-8 motor protein, plays an important role in the regulation of chromosome positioning during cell division and is overexpressed in certain cancers. Certain cancer cells with chromosomal instability (CIN) features depend on KIF18A activity for bipolar spindle integrity and cell proliferation.

Solubility Data

Solubility (In Vitro)

DMSO : 100 mg/mL (177.10 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (4.43 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. 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 (4.43 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	1.7710 mL	8.8550 mL	17.7101 mL
	5 mM	0.3542 mL	1.7710 mL	3.5420 mL
	10 mM	0.1771 mL	0.8855 mL	1.7710 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.