spindle

Alisertib (MLN 8237) is a specific Aurora A inhibitor (IC50: 1.2 nM). The selectivity of Alisertib(MLN 8237) is >200-fold higher for Aurora A than Aurora B.

BAY 1217389 is an effective and selective inhibitor of the monopolar spindle 1 (MPS1) kinase (IC50<10 nM).

AZD-4877 is a potent spindle kinesin (Eg5) inhibitor with an IC50 value of 2 nM. AZD-4877 is an alternative configuration of Ispinesib that inhibits mitosis, induces the formation of a unipolar spindle phenotype, and mediates apoptosis. AZD-4877 has antitumor activity and inhibits circulating peripheral blood mononuclear cells (PBMC).

MKC-1 (Ro-31-7453) is an orally bioavailable small-molecule bisindolylmaleimide cell cycle inhibitor with potential antineoplastic activity. MKC-1 and its metabolites inhibit tubulin polymerization, blocking mitotic spindle formation, which may result in apoptosis and tumor cell death.

Phenytoin (5,5-Diphenylhydantoin) is a hydantoin derivative and a non-sedative antiepileptic agent with anticonvulsant activity. It potentially acts by promoting sodium efflux from neurons in the motor cortex, reducing post-tetanic potentiation at synapses. This prevents cortical seizure foci from spreading to adjacent areas and stabilizes the threshold against hyperexcitability. Additionally, it appears to reduce muscle spindle sensitivity to stretch, causing muscle relaxation.

Podofilox ((+)-Shikonin) is a lignan (LIGNANS) found in PODOPHYLLIN resin from the roots of PODOPHYLLUM plants. It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives.

S-trityl-L-Cysteine is a non-natural amino acid and an inhibitor of Eg5, also known as KSP and Kif11, a mitotic kinesin necessary for mitotic spindle formation. S-trityl-L-Cysteine inhibits the ATPase activity of Eg5 in basal and microtubule-stimulated states (IC50s = 1,000 and 140 nM, respectively). It is selective for Eg5 over nine other human kinesins in an enzyme-coupled assay. It reversibly inhibits Eg5-driven microtubule sliding velocity with an IC50 value of 500 nM using X. laevis recombinant Eg5. It induces cell cycle arrest in HeLa cells (IC50 = 700 nM), reversibly halting the cell cycle in the mitotic phase by inhibiting the separation of duplicated chromosomes and preventing bipolar spindle formation. S-trityl-L-Cysteine inhibits the growth of cancer cells in vitro when tested against the National Cancer Institute (NCI) 60 human cancer cell line panel (average GI50 = 1.3 μM) and in mouse xenograft models.

Vinorelbine (KW-2307 base) is a semisynthetic vinca alkaloid. Vinorelbine binds to tubulin and prevents the formation of the mitotic spindle, resulting in the arrest of tumor cell growth in metaphase.

(R)-Filanesib is the R-enantiomer of ARRY-520. (R)-Filanesib is a synthetic kinesin spindle protein (KSP) inhibitor (IC50: 6 nM).

NMS-P715 is a selective and ATP-competitive MPS1 inhibitor(IC50 of 182 nM).

BOS-172722 is an inhibitor of the monopolar spindle 1 (MPS1) checkpoint with an IC50 of 2 nM.

CCT251455, the mitotic kinase monopolar spindle 1 (MPS1 TTK) inhibitor, is a potent (IC50=3 nM) and specific chemical tool.

Mps1-IN-3 is an effective and selective inhibitor of MPS1 kinase (IC50: 50 nM).

TC-Mps1-12 is an effective and selective inhibitor of monopolar spindle 1 (IC50: 6.4 nM) .

Mps1-IN-2 is a potent, selective, and ATP-competitive inhibitor of both Mps1 and Plk1.

STAT3-IN-31 (compound K2071), derived from STATtic, acts as an inhibitor of both STAT3 and mitotic processes. This compound interrupts mitotic progression and impacts the formation of the mitotic spindle. Additionally, STAT3-IN-31 hampers migration in glioblastoma cells, suppresses cellular proliferation within tumor spheroids, induces senescence in glioblastoma, and inhibits the growth of Temozolomide-resistant cells while reducing the secretion of the pro-inflammatory cytokine monocyte chemoattractant protein (MCP-1).

PROTAC MPS1 Degrader 2 (Compound 15) is a potent degrader of monopolar spindle 1 (Mps1, TTK), AURKA, and AURKB with DC50 values of 42.0, 2.1, and 154.0 nM respectively. It is utilized in the research of acute myeloid leukemia.

PROTAC MPS1 degrader 1 (Compound 19) acts as a potent degrader of Monopolar spindle 1 (Mps1, TTK), AURKA, and AURKB, with DC50 values of 17.7, 108.7, and 570.3 nM respectively. It is utilized in the study of acute myeloid leukemia. (Pink: ligand for target protein; Black: linker; Blue: ligand for E3 ligase)

BNC105P is a benzo[b]furan-based vascular disrupting agent (VDA) prodrug with potential anti-vascular and anti-tumor effects. Upon administration, BNC105P, in its disodium phosphate form, rapidly converts to BNC105. In activated endothelial cells, BNC105 binds to tubulin and inhibits its polymerization, which may block spindle formation, cause cell cycle arrest, and dismantle the tumor vasculature. This creates a hypoxic environment, depriving tumor cells of nutrients, leading to apoptosis. Apart from its VDA activity, BNC105P also exerts direct cytotoxic effects on tumor cells by inhibiting tubulin polymerization. Notably, BNC105 is not a substrate for the multidrug-resistant P-glycoprotein (Pgp) transporter.

TTK PLK1-IN-1 (Formula I) is an inhibitor of threonine tyrosine kinase (TTK) and polo-like kinase 1 (PLK1), with IC50 values of 7 nM and 72 nM, respectively. It regulates the spindle assembly checkpoint (SAC) and exhibits antitumor activity against triple-negative breast cancer (TNBC).

PROTACKSP-IN-1 (Compound 21) is a spindle protein (KSP) degrader as a PROTAC, effectively degrading KSP in HCT-116 cells with a DC50 value of 114.8 nM. It inhibits the proliferation of HCT-116 with an IC50 of 10 nM, causes G2 M phase cell cycle arrest, and induces apoptosis in HCT-116. Additionally, PROTACKSP-IN-1 demonstrates antitumor activity in mouse models.

Lexibulin (CYT-997)(CYT-997) is a potent tubulin polymerization inhibitor (IC50: 10-100 nM, in Y cell lines). Lexibulin blocks the formation of the mitotic spindle and leading to cell cycle arrest at the G2 M phase; this may result in disruption of the tumor vasculature and tumor blood flow, and tumor cell death.

Ispinesib (SB-715992), a selective, effectvie and reversible inhibitor of kinesin spindle protein (KSP), is derived from quinazolinone, with antineoplastic properties.

MK-0731, a synthetic small molecule with potential antineoplastic activity, selectively inhibits kinesin spindle protein (KSP), leading to the inhibition of mitotic spindle assembly, induction of cell cycle arrest during the mitotic phase and apoptosis in