CYT997 (Lexibulin)作用于癌细胞系，是一种有效的microtubule（微管）聚合抑制剂，IC50为10-100 nM。Phase 1/2。CYT997(1 μM)处理A549细胞24小时，诱导微管快速重组，包括现有的微管网络遭破坏，及一些细胞质微管蛋白在菌斑处累积，导致细胞形态发生显著变化，包括粘附细胞丢失，细胞减少。CYT997作用于16种癌细胞具有毒性，IC50为作用于HepG2细胞的9 nM到作用于 KHOS/NP细胞的101 nM。CYT997有效作用于HCT15细胞, 具有多耐药机制Pgp(MDR⁺), IC50为52 nM。

>98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

Lexibulin

Ethanol ：16 mg/mL (36.8 mM)

DMSO ：80 mg/mL (184.1 mM)

Microtubules (cancer cell lines)

CYT997 (1 μM) treatment for 24 hours in A549 cells induces rapid reorganization of microtubules including the destruction of the existing microtubule network and accumulation of tubulin in plaques within the cytoplasm of some cells, leading to significant cell morphology alterations including the loss of adhesion and cell rounding. CYT997 displays potent cytotoxic activity against a range of 16 cancer cells with IC50 ranging from 9 nM for HepG2 to 101 nM for KHOS/NP. Especially, CYT997 exhibits potent activity against HCT15 cells, known to possess the multidrug resistance mechanism Pgp (MDR+), with IC50 of 52 nM. Through inhibition of microtubule polymerization, CYT997 blocks the cell cycle at the G2-M boundary, and induces an increase in phosphorylated Bcl-2 and increased expression of cyclin B1, as well as caspase-3 activation and the generation of poly (ADP-ribose) polymerase. CYT997 treatment causes a rapid and reversible increase in the permeability of HUVEC monolayers with IC50 of ~80 nM at 1 hour of exposure. Consistent with the disruption of cellular tubulin, CYT997 potently inhibits proliferation, induces cell cycle arrest and most importantly apoptosis of both human myeloma cell lines (HMCLs) and primary MM cells.

The half-life of CYT997 for oral administration (2.5 hours) to rats is slightly longer than that for intravenous administration (1.5 hours), with the JPolute oral bioavailability being 50% to 70%. Oral administration of CYT997 induces dose-dependent inhibition of tumor growth of PC3 xenografts in mice, more potently compared with paclitaxel. CYT997 is also effective in an orthotopic syngeneic model using the mouse breast cancer 4T1 cells, which are some refractory to Paclitaxel treatment. A single dose of CYT997 (7.5 mg/kg, i.p.) reduces tumor blood flow significantly at 6 hours in liver metastases, to a similar extent as the positive control CA4P dosed at 100 mg/kg. CYT997 treatment (15 mg/kg/day) significantly prolongs the survival in a murine model of aggressive systemic myelomatosis.