HSP Inhibitor

MK2-IN-1 hydrochloride (compound 1) is a potent and selecitve MAPKAPK2 (MK2) inhibitor with an IC₅₀ of 0.11 uM for MK2 and an EC₅₀ of 0.35 uM for pHSP27. MK2-IN-1 hydrochloride impaires the phosphorylation level of serine residues in the Tfcp2l1 protein.

MAL3-101 is a potent HSP70 allosteric inhibitor. MAL3-101 inhibits HSP70 ATPase activity by blocking Hsp40 co-chaperone interaction. MAL3-101 can be used for researching muscle invasive bladder cancer (MIBC).

NCT-58 is a potent inhibitor of C-terminal HSP90. NCT-58 does not induce the heat shock response (HSR) due to its targeting of the C-terminal region and elicits anti-tumor activity via the simultaneous downregulation of HER family members as well as inhibition of Akt phosphorylation. NCT-58 kills Trastuzumab-resistant breast cancer stem-like cells. NCT-58 induces apoptosis in HER2-positive breast cancer cells.

Icapamespib (PU-HZ151; PU-AD) is a selective, orally active inhibitor of Epichaperomes assembled by HSP90 with slow dissociation kinetics. Icapamespib can cross the blood-brain barrier (BBB) ??and induce epichaperome disassembly by non-covalently binding to HSP90, restoring the normal protein-protein interaction network. Icapamespib can specifically disrupt disease-related abnormal protein interaction networks, reduce neurotoxic protein aggregation and tumor cell survival signals. Icapamespib can be used in the research of neurodegenerative diseases such as Alzheimer's disease, as well as cancers such as glioblastoma and metastatic breast cancer.

Flavokawain C is an orally active natural chalcone. Flavokawain C inhibits the proliferation of various cancer cells. Flavokawain C upregulates GADD153 in cancer cells, inhibits the phosphorylation of Akt and JNK, suppresses early ERK phosphorylation, activates late ERK phosphorylation, activates caspase related subtypes, induces PARP-1 cleavage, causes upregulation of p21 and p27, downregulation of mutant p53 and anti-apoptotic IAP proteins, elevates intracellular ROS levels, reduces SOD activity, and induces apoptosis. Flavokawain C downregulates FABP4, induces autophagy in cancer cells, and activates the AMPK/mTOR pathway. Flavokawain C decreases the expression of glycolysis-related proteins GLUT1 and HK2, and inhibits glycolysis in nasopharyngeal carcinoma cells. Flavokawain C inhibits the activation of the EGFR/PI3K/Akt/mTOR signaling pathway and reduces the expression of HSP90B1. Flavokawain C inhibits angiogenesis by decreasing the expression of angiogenic proteins Ang-1 and VEGF in human umbilical vein endothelial cells. Flavokawain C increases γ-H2AX levels in cells, inhibits the phosphorylation of FAK, PI3K and AKT in cells, and induces DNA damage in cells. Flavokawain C exerts anti-tumor activity in multiple tumor xenograft mouse models. Flavokawain C is applicable to research related to colorectal cancer, colon adenocarcinoma, nephroblastoma, nasopharyngeal carcinoma and liver cancer.

TBPH is a brominated flame retardant. TBPH enhances hepatic steatosis, inflammation, and fibrosis in mice with nonalcoholic steatohepatitis (NASH). TBPH induces dysregulation of phospholipid metabolism, reducing cardiolipin (CL) and phosphatidylserine (PS) levels. TBPH leads to impaired endoplasmic reticulum-mitochondria (ER-Mito) contacts, subsequently causing mitochondrial dysfunction. TBPH induces lung injury through an inflammatory response mediated by mitochondria-derived ds-DNA. TBPH can be used to study the role of MFN2-mediated ER-mitochondria contacts in lipid metabolism homeostasis.

Regaloside C is an anti-inflammatory agent and antioxidant that scavenges ABTS and DPPH free radicals. Regaloside C targets multiple molecules including TNF-α, MMP-2, ERα, AKT1, TLR4 and HSP90-α. Regaloside C is applicable to research related to inflammatory diseases.

DN401 is a potent TRAP1 inhibitor with an IC₅₀ of 79 nM. DN401 shows a weak inhibition of Hsp90 (IC₅₀ of 698 nM). DN401 inactivates mitochondrial TRAP1 and has potent anticancer activities.

GRP78-IN-3 (Compound 8) is a selective Grp78 (HSPA5) inhibitor with an IC₅₀ of 0.59 μM. GRP78-IN-3 is 7-fold selective for HspA5 compared to HspA9 (IC₅₀ of 4.3 μM) and >20-fold selective for HspA5 compared to HspA2 (IC₅₀ of 13.9 μM).

KUNB31 is a selective inhibitor of SP90β with an K_d value of 0.18 μM.

Icapamespib (PU-HZ151; PU-AD) hydrochloride is a selective, orally active inhibitor of Epichaperomes assembled by HSP90 with slow dissociation kinetics. Icapamespib hydrochloride can cross the blood-brain barrier (BBB) ??and induce epichaperome disassembly by non-covalently binding to HSP90, restoring the normal protein-protein interaction network. Icapamespib hydrochloride can specifically disrupt disease-related abnormal protein interaction networks, reduce neurotoxic protein aggregation and tumor cell survival signals. Icapamespib hydrochloride can be used in the research of neurodegenerative diseases such as Alzheimer's disease, as well as cancers such as glioblastoma and metastatic breast cancer.

Ursolic acid acetate (Acetylursolic acid) is a triterpenoid compound and an inhibitor of Plasmodium falciparum heat shock protein 90 (PfHsp90) with a K_D of 8.16 μM. Ursolic acid acetate is cytotoxic to KB cells, with an IC₅₀ value of 8.4 μM. Ursolic acid acetate can be used in tumor and antimalarial research.

MPC-3100 is an orally bioavailable, synthetic, second-generation small-molecule inhibitor of Hsp90 with potential antineoplastic activity.

Nonactin is a macrotetrolide antibiotic and mitochondrial uncoupler with antibacterial, insecticidal, and acaricidal activities. Nonactin acts as an ionophore for monovalent cations, including K⁺, and NH₄⁺, and it can also inhibit the surface expression of endogenous HSP60. In addition, Nonactin can induce apoptosis in β-catenin mutant tumor cells and has anti-tumor activity.

HYOU1-IN-1 (Compound 33) is an inhibitor of hypoxia-upregulated protein 1 (HYOU1) with anti-inflammatory activity. HYOU1-IN-1 can be used in research on the regulation of fibroblast activation, chronic inflammation, and fibrotic diseases.

SNX-0723 is a potent Hsp90 Inhibitor with anti-Plasmodium activity. SNX-0723 shows high binding affinity for HsHsp90 and PfHsp90 with K_is of 4.4 and 47 nM, respectively. SNX-0723 inhibits liver-stage P. berghei ANKA parasites with the EC₅₀ of 3.3 μM.

3-Phenyltoxoflavin, a derivative of Toxoflavin, is an Hsp90 inhibitor, with a K_d of 585 nM for the interaction of Hsp90-TPR2A. 3-Phenyltoxoflavin has anti-cancer activity.

HSP70-IN-1 is a heat shock protein (HSP) inhibitor; inhibits the growth of Kasumi-1 cells with an IC₅₀ of 2.3 μM.

HSP90-IN-23 (Comp 12-1) is an inhibitor of heat shock protein 90(HSP90) with an IC₅₀ of 9 nM. HSP90-IN-23 induces apoptosis of tumor cells and arrests the tumor cell cycle in G0/G1 phase. HSP90-IN-23 can be used for cancer research.

Hsp90-Cdc37-IN-3 (Compound 9) is a novel celastrol−imidazole derivative with anticancer activity. Hsp90-Cdc37-IN-3 inhibits Hsp90−Cdc37 by covalent-binding, and induces apoptosis.