polymerization

Voxelotor (GBT 440) is a novel hemoglobin S (HbS) polymerization inhibitor primarily used for the treatment of sickle cell disease (SCD) and a cytochrome P450 3A4 inhibitor. Voxelotor targets and covalently binds to the N-terminal valine of the HbS alpha chain, thereby stabilizing sickle cell hemoglobin (HbS).

Batabulin (T138067) is an antitumor compound that binds covalently and selectively to a subset of the β-tubulin isotypes, disrupting microtubule polymerization. This disruption affects cell morphology, induces cell-cycle arrest, and ultimately leads to apoptotic cell death.

(±)-Decursinol (3',4'-dihydro-3'-hydroxy-Xanthyletin) is a natural product from Angelica gigas.

Map4343 is a 3-methyl ether derivative of pregnenolone. Map4343 binds to microtubule associated protein 2 (MAP2) in vitro and stimulates tubulin polymerization, resulting in enhanced neurite extension and protection of neurons from neurotoxic agents.

GPRP acetate (Pefabloc FG) is fibrinogen-related peptides, which inhibit the interaction of fibrinogen with the platelet membrane glycoprotein IIbIIIa complex (GPIIbIIIa).

Tubulin polymerization-IN-47 is a tubulin polymerization inhibitor and mitotic inhibitor with antitumor activity and inhibitory effects on neuroblastoma cancer cell proliferation, with IC50s of 7 and 12 nM for Chp-134 and Kelly cell lines, respectively. Tubulin polymerization-IN-47 is a candidate compound for the treatment of hepatocellular carcinoma, colon cancer, lung cancer and breast cancer.

Tubulin polymerization-IN-55 is a potent Tubulin Polymerization inhibitor with potential anti-angiogenic and anti-tumor activity, demonstrating anti-proliferative effects against A549, K562, HepG2, MDA-MB-231, and HFL-1.

Tubulin polymerization-IN-68 (compound 32) serves as a tubulin inhibitor, disrupting cellular microtubule networks by hindering tubulin polymerization. It also upregulates PARP-1 and caspase-3 expression, thereby inducing apoptosis and exhibiting anticancer properties. Notably, Tubulin polymerization-IN-68 effectively suppresses HepG2 cells with an IC50 of 93 nM and markedly reduces the growth of HepG2 xenograft tumors in nude mice through oral administration.

Tubulin polymerization-IN-69 (compound 6c) exhibits significant inhibition of microtubule assembly in vitro, with an inhibition rate of 78.3% and an IC50 value of 6.53 μM. It rapidly induces apoptosis and G2 M phase cell cycle arrest in MCF-7 cells.

Tubulin polymerization-IN-70 (compound Q19) is an effective inhibitor of tubulin polymerization. This compound exerts antiproliferative properties by targeting the colchicine binding site on tubulin, thereby inhibiting its polymerization. Tubulin polymerization-IN-70 also induces apoptosis and cell cycle arrest at the G2 M phase. Additionally, it triggers a decrease in mitochondrial membrane potential and elevates levels of reactive oxygen species (ROS). Moreover, Tubulin polymerization-IN-70 possesses anti-angiogenic and anticancer activities.

Tubulin Polymerization-IN-1 prodrug (Compound 2b) is a microtubule polymerization inhibitor prodrug mediated by Pd. Developed from colchicine-binding site inhibitors (CBSIs), it aims to reduce toxicity and enhance targeted release. Compared to the parent compound, its cytotoxicity is decreased by 68.3 times, but can be in situ restored in the presence of Pd resin. Mechanistic studies show it retains the same antitumor activity as CBSIs. In vivo tests demonstrate that, once activated by Pd resin, it significantly suppresses tumor growth (63.2% inhibition rate). Tubulin Polymerization-IN-1 prodrug is a promising candidate for cancer research.

Tubulin polymerization-IN-71 (Compound 4k) is an inhibitor of tubulin polymerization with an IC50 of 3.06 μM. It suppresses the proliferation of cancer cells MG-63 and U2OS, with an IC50 ranging from 0.08 to 0.14 μM. Additionally, Tubulin polymerization-IN-71 induces cell cycle arrest at the G2 M phase and triggers apoptosis in MG-63 cells.

Tubulin polymerization-IN-73 (Compound 37) is an inhibitor of microtubule polymerization with an IC50 of 1.8 μM. It induces cell cycle arrest at the G2 M phase and triggers apoptosis in A549 cells. The compound inhibits the proliferation of both A549 WT and A549 T resistant cells with IC50 values of 0.023 μM and 0.057 μM, respectively. Additionally, Tubulin polymerization-IN-73 demonstrates antitumor activity in mouse models.

Tubulin polymerization-IN-75 (Compound 6) is an inhibitor of tubulin polymerization, with an IC50 value of 30 μM. It effectively suppresses the proliferation of cancer cells Huh7 and 293T, demonstrating IC50 values of 14.3 μM and 13.8 μM, respectively.

Tubulin polymerization-IN-74 (compound 11) is an inhibitor of tubulin polymerization, with an IC50 value of 15 μM. It is applicable to cancer research.

Tubulin polymerization-IN-72 (Compound 4a4) is a microtubule synthesis inhibitor with anticancer properties. By binding to the colchicine site, it disrupts the polymerization of tubulin, resulting in the arrest of cancer cells at the G2 M phase and inducing apoptosis (Apoptosis). The IC50 for its activity against cancer cells is 0.4-2.7 nM.

Tubulin polymerization-IN-76 (compound 20b) is a potent and orally active inhibitor of tubulin polymerization. It acts at the colchicine binding site to inhibit tubulin polymerization with an IC50 value of 2.505 μM, effectively disrupting the intracellular microtubule network and interfering with mitosis. Tubulin polymerization-IN-76 shows significant inhibitory effects on MGC-803 and HGC-27 cells, with IC50 values of 1.61 and 1.82 nM, respectively. It effectively suppresses colony formation and cell migration activities in these cell lines, inducing G2 M phase cell cycle arrest and apoptosis (Apoptosis). Furthermore, Tubulin polymerization-IN-76 exhibits broad-spectrum antiproliferative activity.

Tubulin polymerization-IN-77 (Compound 15c) is a microtubule polymerization inhibitor that exhibits anti-glioblastoma activity by hindering microtubule polymerization. It demonstrates significant blood-brain barrier permeability, effectively induces G2 M phase arrest in GBM cells, and triggers apoptosis, while also markedly inhibiting tumor cell migration.

α-Tubulin polymerization-IN-1 (Compound 8l) functions as an inhibitor of α-tubulin polymerization. This compound modulates the NRF2/KEAP-1 signaling pathway and induces ROS production in PC-3 cells, leading to apoptosis. It inhibits the proliferation of PC-3 cells with a GI50 of 0.17 µM, causing cell cycle arrest in the G2/M phase. Additionally, α-Tubulin polymerization-IN-1 demonstrates antitumor activity in mouse models.

Tubulin polymerization-IN-78 (compound 10a) is an inhibitor of tubulin polymerization, with an IC50 value of 2.69 μM. It exhibits antiproliferative activity.

Tubulin polymerization-IN-14 (Compound 20a) is a tubulin polymerization inhibitor (IC50 = 3.15 μM) that demonstrates strong anti-vascular and anticancer activities, including inducing cancer cell apoptosis [1].

Tubulin polymerization-IN-22 arrests cell cycle at G2 M phase as well as induces apoptosis. Tubulin polymerization-IN-22 is an inhibitor of tubulin polymerization (IC 50 = 8.1 μM) [1].

Tubulin polymerization-IN-36 is able to be used in cancer research, for example, lymphomas. Tubulin polymerization-IN-36 binds to the colchicine site of tubulin and inhibits colchicine binding, that is an inhibitor of tubulin polymerization with IC50 of 2.8 μΜ[1].

Tubulin Polymerization-IN-2 is a powerful anticancer agent that targets β-tubulin, exhibiting an IC 50 of 0.92 μM. It demonstrates promising efficacy against a range of cancer cell lines including leukemia, non-small cell lung, renal, prostate, and breast cancers [1].