Dynamin Inhibitor

Mdivi-1 is a selective dynamin-related protein 1 (Drp1) inhibitor. Mdivi-1 is a mitochondrial division/mitophagy inhibitor.

Dynasore is a cell-permeable dynamin inhibitor with an IC₅₀ of 15 μM. Dynasore blocks cell migration.

Hydroxy Dynasore (Dyngo-4a), a structural mimetic analog of Dynasore (HY-15304), is an improved, less cytotoxic and versatile dynamin inhibitor with IC₅₀ values ​​of 0.38 μM and 2.3 μM for brain recombinant dynamin I and recombinant mouse dynamin II, respectively. Hydroxy Dynasore inhibits dynamin-dependent transferrin endocytosis with an IC₅₀ of 5.7 μM.

Schaftoside is a flavonoid found in a variety of Chinese herbal medicines, such as Eleusine indica. Schaftoside inhibits the expression of TLR4 and Myd88. Schaftoside also decreases Drp1 expression and phosphorylation, and reduces mitochondrial fission.

ES9-17 is an analog of ES9 (endosidin9), which is an inhibitor of clathrin heavy chain (CHC). ES9-17 is an inhibitor of clathrin-mediated endocytosis (CME), a major route for internalization of plasma membrane proteins and molecules from the extracellular environment in plants. ES9-17 inhibits the uptake of transferrin and FM4-64. ES9-17 also inhibits root growth of Arabidopsis seedings.

Tyrphostin AG 537 is a dynamin I GTPase inhibitor with an IC₅₀ of 1.7 μM. Tyrphostin AG 537 inhibits phospholipid-stimulated GTPase activity without competing for the GTP domain or PH domain of dynamin I. Tyrphostin AG 537 inhibits spermidine-induced autoactivation of pro-plasma hyaluronan-binding protein (pro-PHBP) with an IC₅₀ of 0.018 μM. Tyrphostin AG 537 can be used in inflammation-related research.

P110 heptapeptide is a peptide inhibitor of the Drp1-Fis1 interaction. P110 heptapeptide has anti-inflammatory, immunomodulatory, mitochondrial protective, and neuroprotective activities. Without blocking the physiological functions of Drp1, P110 heptapeptide reduces pathological functions in many models of neurodegeneration, ischemia, and sepsis. P110 heptapeptide can be used for research on neurological and inflammatory diseases.

Dynole 34-2 is a potent dynamin GTPase inhibitor (IC₅₀s=6.9 and 14.2 µM for dynamin1 and dynamin2 GTPase activity, respectively) with antimitotic effect. Dynole 34-2 induces apoptosis, as revealed by cell blebbing, DNA fragmentation, and PARP cleavage. Dynole 34-2 also potently inhibits receptor mediated endocytosis (RME).

TAT-P110, a peptide inhibitor of Drp1-Fis1 interaction, reduces pathology in numerous models of neurodegeneration, ischemia, and sepsis without blocking the physiological functions of Drp1.

Bleomycin A5 (Pingyangmycin) is a glycopeptide antibiotic with multiple biological activities, which can be isolated from Streptomyces. Bleomycin A5 exerts cytotoxic effects by binding to Fe²⁺ to form a complex, inducing single-strand and double-strand DNA breaks, and inhibiting DNA replication. Bleomycin A5 inhibits Drp1-mediated mitochondrial fission and suppresses PINK1/Parkin pathway-mediated mitophagy, ultimately triggering mitochondria-mediated cellular apoptosis. Bleomycin A5 can be used in cancer research.

Dynole 2−24 is an indole-based dynamin GTPase inhibitor (IC₅₀=0.56 μM for dynamin I). Dynole 2−24 is nontoxic and shows increased potency against dynamin I and II in vitro and in cells (IC_₅₀(CME)=1.9 μM). Dynole 2−24 also shows 4.4-fold selectivity for dynamin I. Dynole 2−24 is active in-cell inhibitor of clathrin-mediated endocytosis. CME: Clathrin mediated endocytosis

DRP1i27 is a potent inhibitor of human Drp1 (dynamin-related protein 1). DRP1i27 binds to the GTPase site of Drp1, with hydrogen bonds to Gln34 and Asp218. DRP1i27 targets Drp1-mediated mitochondrial fission in cell line models and protects against simulated ischemia-reperfusion injury.

Drpitor1a is a potent Drp1 inhibitor. Drpitor1a inhibits mitochondrial ROS production, preventes mitochondrial fission, and improves right ventricular diastolic dysfunction during IR (ischemia reperfusion) injury. Drpitor1a has the potential for the research of lung cancer^[1]

Dynapyrazole A is a specific inhibitor of microtubule dynamin that specifically inhibits the ATPase activity of microtubule-stimulated dynamin without blocking microtubule-independent basal activity.

POSH-IN-2 (MIDI), a mitochondrial division inhibitor, is a DRP1 inhibitor that potently blocks mitochondrial fragmentation induced by cellular stresses and genetic mitochondrial lesions. POSH-IN-2 covalently interacts with DRP1-C367 to target DRP1 interaction with multiple receptors.

Opitor-0 is a potent and selective inhibitor of mitochondrial dynamin-related protein Optic Atrophy 1 (OPA1) guanosine triphosphatase (GTPase) with an IC₅₀ of 3 μM. Opitor-0 can induce fragmentation of mitochondria and remodeling of cristae, disrupt the stability of OPA1 oligomers, and significantly enhance the release of cytochrome c and induce apoptosis. Opitor-0 has a synergistic antitumor effect with Bcl-2 inhibitors, such as ABT-737 (HY-50907) and Venetoclax (HY-15531). Opitor-0 can be used for the research of malignant tumors that are resistant to Bcl-2 inhibitors, such as triple-negative breast cancer (TNBC).

Clathrin-IN-4 (compound 8b), a Wiskostatin?(HY-12534) analogue, is a potent inhibitor of clathrin mediated endocytosis with an IC₅₀ of 2.1 μM. Clathrin-IN-4 is a dynamin I GTPase activity inhibitor with an IC₅₀ of 9.1 μM.

SP11 is a mitochondrial fission protein 1 (Fis1) inhibitor with an IC₅₀ of 9.4 μM. SP11 binds only to activated Fis1 by engaging Cys41. SP11 preserves mitochondrial integrity and function during oxidative stress, inhibits hydrogen peroxide-induced mitochondrial ROS production, mitochondrial fragmentation, and Drp1 mitochondrial translocation. SP11 can be used for the research of parkinson’s disease.

nti-inflammatory agent 49 (compound SC9) is a quite potent and selective inhibitor of Drp1-Fis1 interaction and can reduce FIS1-mediated mitochondrial dysfunction. The IC₅₀ of SC9 inhibiting GTPase in vitro is 270 nM.

P259 is a Drp1-Mff inhibitor. P259 distinguishes physiological from pathological fission by specifically inhibiting Drp1-Mff interaction. P259 elongates cell mitochondria and disrupts mitochondrial function and motility. P259 reduces ATP levels and alters mitochondrial structure in the brain, resulting in behavioral deficits in wild-type mice and a short lifespan in Huntington's disease (HD) mice model.