VEGFR2 (IC50 = 1 nM); RET (IC50 = 13 nM)

Apatinib significantly and dose-dependently inhibits the growth of a variety of human tumor xenografts. The ABCB1-mediated MDR in the nude mouse xenograft model is reversed by aparinib. Apatinib dramatically increases doxorubicin's antitumor activity in nude mice that have K562/ADR xenografts [3]

Apatinib significantly and dose-dependently inhibits the growth of a variety of human tumor xenografts. The ABCB1-mediated MDR in the nude mouse xenograft model is reversed by aparinib. Apatinib dramatically increases doxorubicin's antitumor activity in nude mice that have K562/ADR xenografts.[3]

The substrate solution containing tyrosine is a poly(glu, ala, tyr) 6:3:1 random copolymer. In order to coat 96 well plates (100 L/well), the substrate is kept as a 1 mg/mL stock in PBS at 20 °C and diluted 1 in 500 with PBS. The day before the assay, plates are coated, sealed with adhesive seals, and kept at 4 °C for the entire night. The substrate solution is disposed of on the day of the assay, and the assay plate wells are twice washed—once with Hepes buffer (50 mM, pH 7.4) and once with PBST (PBS containing 0.05% v/v Tween 20). The assay plates are washed and the test compounds are diluted with 10% dimethylsulfoxide (DMSO) de-ionized water, with 25 μL volumes being transferred to the wells. All test wells are then filled with 25 μL of a manganese chloride solution (40 mM) containing 8 μM ATP. To find the assay's dynamic range, additional wells are added that contain blank and control solutions, respectively, containing manganese chloride solution with and without ATP and compound diluent. Each well receives 50 L of freshly diluted enzyme, which is then added. The plates are then left to sit at room temperature for 20 min. Subsequently, the liquid is disposed of and the wells are twice cleaned using PBST. After adding 100 L/well of mouse IgG anti-phosphotyrosine antibody diluted 1:6000 with PBST containing 0.5% (w/v) bovine serum albumin (BSA), the plates were incubated for 1h at room temperature before the liquid was discarded and the wells were twice washed with PBST. The sheep anti-mouse Ig antibody linked to horseradish peroxidase (HRP) is diluted 1:500 with PBST containing 0.5% (w/v) BSA. After adding 100 μL/well, the plates are incubated for an additional hour at room temperature. The liquid is then discarded, and the wells are twice washed with PBST. Freshly prepared 50 mM phosphate-citrate buffer (pH 5.0) containing 0.03% (w/v) sodium perborate is mixed with 1 mg/mL of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid, and 100 μL is added to each well. The plates are then incubated at room temperature for 20 to 60 minutes, or until the control wells' optical density value, measured at 405 nm, is roughly 1.0. Microcal Origin is used to interpolate IC50 values for compound enzyme inhibition after subtracting blank values.

In 96-well plates, the HUVEC are seeded. The test agents (vehicle serving as the control) are added to the cells along with 20 ng/mL VEGF or 20% FBS and incubated for an additional 72 hours. Following 10% trichloroacetic acid fixation, the cells are stained for 30 minutes at 37 °C using 0.4% sulforhodamine B, and then they are cleaned with 1% acetic acid. After dissolving the complex with tris, the optical density is measured at 520 nM.

Ls174t, HCT 116, SGC-7901, HT-29, A549, NCI-H460 xenografted BALB/cA nude mice
50, 100, 200 mg/kg
p.o.

[1]. Cancer Sci . 2011 Jul;102(7):1374-80.

[2]. Cancer Res . 2010 Oct 15;70(20):7981-91.

[3]. Biochem Pharmacol . 2012 Mar 1;83(5):586-97.

C25H27N5O4S

493.58

493.17837553

C, 60.83; H, 5.51; N, 14.19; O, 12.97; S, 6.50

1218779-75-9

1218779-89-5 (HCl);1218779-75-9 (mesylate);811803-05-1;

white solid powder

CS(=O)(=O)O.C1CCC(C1)(C#N)C2=CC=C(C=C2)NC(=O)C3=C(N=CC=C3)NCC4=CC=NC=C4

FYJROXRIVQPKRY-UHFFFAOYSA-N

InChI=1S/C24H23N5O.CH4O3S/c25-17-24(11-1-2-12-24)19-5-7-20(8-6-19)29-23(30)21-4-3-13-27-22(21)28-16-18-9-14-26-15-10-18;1-5(2,3)4/h3-10,13-15H,1-2,11-12,16H2,(H,27,28)(H,29,30);1H3,(H,2,3,4)

N-[4-(1-cyanocyclopentyl)phenyl]-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide;methanesulfonic acid

YN968D1 mesylate; YN-968D1 mesylate; YN 968D1 mesylate; Rivoceranib mesylate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)