Arp2/3 Complex Inhibitor

Cytochalasin D (Zygosporin A) is a potent actin polymerization inhibitor, could be derived from fungus. Cytochalasin D has cell-permeable activity. Cytochalasin D inhibits the G-actin–cofilin interaction by binding to G-actin. Cytochalasin D also inhibits the binding of cofilin to F-actin and decreases the rate of both actin polymerization and depolymerization in living cells. Cytochalasin D can reduce exosome release, in turn reducing the amount of survivin present in the tumour environment. Cytochalasin D induces phosphorylation and cytoplasmic retention of Yap.

CK-666 is a cell-permeable actin-related protein Arp2/3 complex inhibitor (IC₅₀=12 μM). CK-666 binds to Arp2/3 complex, stabilizes the inactive state of the complex, blocking movement of the Arp2 and Arp3 subunits into the activated filament-like (short pitch) conformation.

SMIFH2 is a formin specific inhibitor. SMIFH2 inhibits actin polymerization by Formins and affects the actin cytoskeleton.

Latrunculin A (LAT-A), found in the red sea sponge Latrunculia magnifica, is a G-actin polymerization inhibitor. Latrunculin A binds to actin monomers and inhibits polymerization of actin with K_ds of 0.1, 0.4, 4.7 μM and 0.19 μM for ATP-actin, ADP-Pi-actin, ADP-actin and G-actin, respectively. Latrunculin A has effective anti-metastatic properties for cancer research. Latrunculin A blocks cell migration.

CK-869 is an Actin-Related Protein 2/3 (ARP2/3) complex inhibitor, with an IC₅₀ of 7 μM.

Wiskostatin is a potent and selective inhibitor of neuronal Wiskott-Aldrich syndrome protein (N-WASP)-mediated actin polymerization by stabilization of the closed, autoinhibited conformation, thereby preventing Arp2/3 complex activation. Wiskostatin is also a dynamin inhibitor with an IC₅₀ value of 20.7 μM and a potent inhibitor of clathrin-mediated endocytosis with an IC₅₀ value of 6.9 μM. Wiskostatin causes a rapid, profound, and irreversible decrease in cellular ATP levels. Wiskostatin also induces disassembly of podosomes in a murine monocyte cell line.

Benproperine phosphate is an orally active, potent actin-related protein 2/3 complex subunit 2 (ARPC2) inhibitor. Benproperine phosphate attenuates the actin polymerization rate of action polymerization nucleation by impairing Arp2/3 function. Benproperine phosphate has the potential for a cough suppressant and suppresses cancer cell migration and tumor metastasis.

CK-636 is a cell permeable inhibitor of Arp2/3 complex, that could inhibit actin polymerization, with IC₅₀ values of 4 μM, 24 μM and 32 μM for human, fission yeast and bovine, respectively. CK636 blocks cell migration.

NSC305787 is an inhibitor of ezrin with a K_d of 5.85 μM, inhibits the phosphorylation of ezrin caused by PKCΙ with an IC₅₀ of 8.3 μM, has antitumor activity.

NSC305787 hydrochloride is an inhibitor of ezrin with a K_d of 5.85 μM, inhibits the phosphorylation of ezrin caused by PKCΙ with an IC₅₀ of 8.3 μM, has antitumor activity.

BDP-13176 is a potent fascin 1 inhibitor, with a K_d of 90 nM and an IC₅₀ of 240 nM. BDP-13176 has potential as an anti-metastatic agent.

TR-100 is a small molecule inhibitor of tumor-associated troponin (Tpm). TR-100 affects the interaction of Tpm3.1 with actin filaments by binding to the C-terminal of Tpm3.1, thereby affecting the stability and function of the actin filaments. This mechanism of action allows TR-100 to specifically affect actin filaments in cancer cells without compromising heart muscle function. TR-100 can be used to study the role of Tpm3.1 in cancer cell proliferation and survival and the effects of Tpm3.1 on insulin-stimulated glucose uptake and insulin secretion.

187-1, N-WASP inhibitor, a 14-aa cyclic peptide, is an allosteric neural Wiskott-Aldrich syndrome protein (N-WASP) inhibitor. 187-1, N-WASP inhibitor potently inhibits actin assembly induced by phosphatidylinositol 4,5-bisphosphate (PIP2) with an IC₅₀ of 2 μM. 187-1, N-WASP inhibitor prevents the activation of Arp2/3 complex by N-WASP by stabilizing the autoinhibited state of the protein.

CK-548 (CK-0993548) is a Arp2/3 complex inhibitor with the IC₅₀ of 11 μM. CK-548 inhibits HIV-1 nuclear migration and infection.

Spire2/FMN2 PPI-IN-1 (Compound 13) is a selective inhibitory fragment targeting the Spire2-FMN2 interaction, with an IC₅₀ of 62 μM. Spire2/FMN2 PPI-IN-1 has affinity for KIND2, with a K_d of 87.7 μM, and does not inhibit KIND1. Spire2/FMN2 PPI-IN-1 can be used for the development of chemical probes for the Spire2-FMN2 interaction.

Spire2/FMN2 PPI-IN-1 (Compound 13) dihydrochloride is a selective inhibitory fragment targeting the Spire2-FMN2 interaction, with an IC₅₀ of 62 μM. Spire2/FMN2 PPI-IN-1 dihydrochloride has affinity for KIND2, with a K_d of 87.7 μM, and does not inhibit KIND1. Spire2/FMN2 PPI-IN-1 dihydrochloride can be used for the development of chemical probes for the Spire2-FMN2 interaction.

PLH1215 is a compound used to regulate, limit, or inhibit the expression of AVIL (advillin), which can be utilized in cancer research.

19-O-Acetylchaetoglobosin A, a cytochalasan alkaloid, is a fungal metabolite originally isolated from C. globosum that has actin polymerization inhibitory and cytotoxic activities. 19-O-Acetylchaetoglobosin A is cytotoxic to HeLa cervical cancer cells.

187-1, N-WASP inhibitor TFA, a 14-aa cyclic peptide, is an allosteric neural Wiskott-Aldrich syndrome protein (N-WASP) inhibitor. 187-1, N-WASP inhibitor TFA potently inhibits actin assembly induced by phosphatidylinositol 4,5-bisphosphate (PIP2) with an IC₅₀ of 2 μM. 187-1, N-WASP inhibitor TFA prevents the activation of Arp2/3 complex by N-WASP by stabilizing the autoinhibited state of the protein.

6,7-Epoxy-latrunculin A can be isolated from the Red Sea sponge Negombata magnifica and is initially identified as an inhibitor of actin polymerization by its morphological effects.