PF-2771 is a selective centromere protein E (CENP-E) inhibitor (antagonist) with IC50 of 16.1 nM and anti-tumor activity.

Physicochemical Properties

Molecular Formula	C29H36CLN5O4
Molecular Weight	554.08
Exact Mass	553.245
CAS #	2070009-55-9
PubChem CID	118704759
Appearance	White to off-white solid powder
Density	1.22±0.1 g/cm3(Predicted)
LogP	3.8
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	12
Heavy Atom Count	39
Complexity	820
Defined Atom Stereocenter Count	1
SMILES	CC(C)OC1=C(C=C(C=C1)C(=O)N[C@@H](CC2=CC=C(C=C2)C3=CN(C(=N3)C(=O)C)C)CNC(=O)CN(C)C)Cl
InChi Key	VHBJNUOZEQTSNN-QHCPKHFHSA-N
InChi Code	InChI=1S/C29H36ClN5O4/c1-18(2)39-26-12-11-22(14-24(26)30)29(38)32-23(15-31-27(37)17-34(4)5)13-20-7-9-21(10-8-20)25-16-35(6)28(33-25)19(3)36/h7-12,14,16,18,23H,13,15,17H2,1-6H3,(H,31,37)(H,32,38)/t23-/m0/s1
Chemical Name	N-[(2S)-1-[4-(2-acetyl-1-methylimidazol-4-yl)phenyl]-3-[[2-(dimethylamino)acetyl]amino]propan-2-yl]-3-chloro-4-propan-2-yloxybenzamide
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	CENP-E 16.1 nM (IC50)
ln Vitro	With an IC50 of 16.1 nM, PF-2771 is a strong and specific inhibitor of CENP-E that inhibits CENP-E motor activity. The ATPase activities of closely related kinesins are not inhibited by PF-2771 (0% inhibition of MCAK, chromokinesin, and Eg5/KSP at both 1 and 10 μM PF-2771). 74 protein kinases are inactively inhibited by PF-2771 (all <23% inhibition at 1 μM, <40% at 10 μM PF-2771). With EC50s of less than 0.1 μM, PF-2771 is cytotoxic to the basal-like breast cancer tumor cell survival; however, it has no effect on normal or premalignant cell lines (EC50 > 5 μM). In MDA-MB-468 cells, PF-2771 (100 nM) causes a chromosomal congression defect[1].
ln Vivo	In SCID mice with AA1077 mammary tumors, PF-2771 (100 mg/kg, intraperitoneally every day) potently suppresses CENP-E motor activity and promotes tumor regression[1].
References	[1]. Chemogenetic evaluation of the mitotic kinesin CENP-E reveals a critical role in triple-negative breast cancer. Mol Cancer Ther. 2014 Aug;13(8):2104-15.

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 32 mg/mL (57.75 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.51 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 (4.51 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 (4.51 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	1.8048 mL	9.0240 mL	18.0479 mL
	5 mM	0.3610 mL	1.8048 mL	3.6096 mL
	10 mM	0.1805 mL	0.9024 mL	1.8048 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.