LP-261 is a novel and potent mitotic/tubulin inhibitor with potential anticaner activities. Cell cycle arrest at G2/M phase is achieved by blocking tubulin polymerization.

Physicochemical Properties

Molecular Formula	C22H19N3O4S
Molecular Weight	421.47
Exact Mass	421.11
Elemental Analysis	C, 62.69; H, 4.54; N, 9.97; O, 15.18; S, 7.61
CAS #	915412-67-8
Related CAS #	915412-67-8
PubChem CID	15603282
Appearance	White to off-white solid powder
LogP	4.994
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	6
Heavy Atom Count	30
Complexity	710
Defined Atom Stereocenter Count	0
SMILES	COC1=NC=CC(=C1)C(=O)C2=CC(=CC(=C2)C3=C4C=CNC4=CC=C3)NS(=O)(=O)C
InChi Key	YUVDELGTFILMBB-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H19N3O4S/c1-29-21-13-14(6-8-24-21)22(26)16-10-15(11-17(12-16)25-30(2,27)28)18-4-3-5-20-19(18)7-9-23-20/h3-13,23,25H,1-2H3
Chemical Name	N-[3-(1H-indol-4-yl)-5-(2-methoxypyridine-4-carbonyl)phenyl]methanesulfonamide
Synonyms	LP261; LP-261; LP 261
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	tubulin polymerization (EC50 = 3.2 μM)
ln Vitro	LP-261 shows a range of activity from 0.01μM to 0.38μM across the tested cell lines, and demonstrates potent G2/M block activity in multiple of them. The IC50 values for MCF-7, H522, Jurkat, SW-620, BXPC-3, and PC-3 are 0.01μM, 0.01μM, 0.02μM, 0.05μM, 0.05μM, and 0.07μM, respectively[1]. LP-261 demonstrates low micromolar potency; its EC50 value is 5.0 μM in the tubulin polymerization assay[1]. In a [3H]colchicine competition binding assay, LP-261 can rival colchicine for binding to tubulin. Its EC50 (3.2 μM) indicates that it can inhibit binding with a potency comparable to that of colchicine, and it can exhibit a 79% inhibition at a concentration of 30 μM[1].
ln Vivo	LP-261 (oral gavage; 4 mg/kg; single dose) exhibits a moderate rate of elimination in rats, with a terminal half-life of 1.4 hours (0.2 hours) indicating rapid oral adsorption (Tmax=2.0 h), and a volume of distribution (Vss) of 1.25 L/kg[1]. LP-261 (oral gavage; 15 or 50 mg/kg; twice daily; 28 days) at 50 mg/kg causes an approximate tumor volume of 130 mm3, which is 96% less than the mean tumor volume in the vehicle treated group, which was 3769 mm3. In this mouse model, LP-261 at 15 mg/kg results in a 41% inhibition after 28 days[1].
Animal Protocol	Human tumor xenograft model (Injected with NCI-H522 human non-small-cell) in NCr-nu mice[1] 15 or 50 mg/kg Oral gavage; 15 or 50 mg/kg; twice daily; 28 days
References	[1]. Synthesis and pharmacological evaluation of N-(3-(1H-indol-4-yl)-5-(2-methoxyisonicotinoyl)phenyl)methanesulfonamide (LP-261), a potent antimitotic agent. J Med Chem. 2011 Jan 13;54(1):179-200 .

Solubility Data

Solubility (In Vitro)

DMSO: ~33.3 mg/mL (~79.1 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.93 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 2: ≥ 2.5 mg/mL (5.93 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	2.3726 mL	11.8632 mL	23.7265 mL
	5 mM	0.4745 mL	2.3726 mL	4.7453 mL
	10 mM	0.2373 mL	1.1863 mL	2.3726 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.