p97 Inhibitor

CB-5083 is a first-in-class, potent, selective, and orally bioavailable inhibitor of the p97 AAA ATPase/VCP. CB-5083 selectively inhibits p97 through its D2 site with the IC₅₀ of 11 nM.

NMS-873 is a potent, selective allosteric VCP/p97 inhibitor with an IC₅₀ value of 30 nM.

Eeyarestatin I, a potent endoplasmic reticulum-associated protein degradation (ERAD) inhibitor, is a potent protein translocation inhibitor. Eeyarestatin I inhibits Sec61 translocon. Eeyarestatin I targets the p97-associated deubiquitinating process (PAD) and inhibits atx3-dependent deubiquitination. Eeyarestatin I interferes at a step prior to proteasomal degradation. Eeyarestatin I induces cell death via the proapoptotic protein NOXA and has anticancer effects.

DBeQ is a selective, potent, reversible, and ATP-competitive p97 inhibitor, with an IC₅₀ value of 1.5 μM and 1.6 μM for p97(wt) and p97(C522A), respectively; DBeQ also inhibits Vps4 with an IC₅₀ of 11.5 μM.

MSC1094308 is a non-competitive and reversible VPS4B/p97 (VCP) (I/II type AAA ATPase) allosteric inhibitor, with IC₅₀ values of 0.71 μM and 7.2 μM for VPS4B and p97, respectively. MSC1094308 inhibits the D2 ATPase activity by binding to a agentable hotspot of p97. MSC1094308 can be used in study of cancer.

ATI-1 is an autophagy initiation inhibitor. ATI-1 targets valosin-containing protein (VCP/p97, disrupts its interaction with UFL1, impairs UFMylation homeostasis associated with VCP, promotes polyubiquitination and degradation of Beclin1, and blocks the formation of early autophagosomes. ATI-1 induces synergistic death of autophagy-dependent malignant tumor cells under nutrient deprivation conditions, accompanied by decreased mitochondrial membrane potential, reduced ROS levels and lysosomal stress. ATI-1 exhibits anti-tumor efficacy in a pancreatic adenocarcinoma xenograft mouse model. ATI-1 can be used for the research of pancreatic adenocarcinoma and lung cancer.

SMDC818909 is an indole amide-derived uncompetitive inhibitor targeting p97 AAA+ ATPase, with an IC₅₀ of 3.5 μM and a K_a of 9.1 μM. SMDC818909 binds to the D2 ATPase domain of p97, preferentially associates with the ADP-bound conformation of p97, allosterically blocks the ATP hydrolysis cycle of p97, and inhibits its mediated intracellular protein homeostasis regulatory function. SMDC818909 is applied to the research and development of p97-targeted antitumor drugs, as well as studies on cancer-related proteotoxic stress mechanisms.

LC-1028 (Compound 20) is an irreversible, non-competitive, covalent p97 inhibitor with a Ki^app value of 33.2 nM. LC-1028 covalently modifies the cysteine residues (Cys105, Cys522, Cys535) of p97. LC-1028 can be used in the research of pancreatic cancer.

CB-5339 is an oral activity potent p97 inhibitor with an IC₅₀ <30 nM. CB-5339 can be used for leukemia research. CB-5339 extracted from WO2015109285A1 compound FF07.

ML240 is a potent p97 inhibitor, inhibiting p97 ATPase with IC₅₀ value of 100 nM.

UPCDC-30245 is an allosteric p97 inhibitor with an IC₅₀ of approximately 27 nM. UPCDC-30245 inhibits the p97 mutant N660K similar to wild type (WT; IC₅₀=300 nM) and shows 3-fold resistance for p97 mutant T688A. UPCDC-30245 can be used in the research of cancer.

ML241 is a potent, selective and competitive p97 ATPase inhibitor with an IC₅₀ of 0.11 μM. ML241 can be used for the research of cancer.

NMS-859 is a potent, covalent VCP (p97) inhibitor, with IC₅₀s of 0.37 and 0.36 μM for wild-type VCP in the presence of 60 μM and 1 mM ATP in cells, respectively.

ML241 hydrochloride is a potent p97 inhibitor, inhibiting p97 ATPase with IC₅₀ value of 100 nM.

UPCDC30766 is a potent allosteric inhibitor of p97 (IC₅₀ of 12 nM; EC₅₀ of 0.23 μM in cells). UPCDC30766 can be used for the research of colon cancer.

NPD8733 is an inhibitor of cancer cell-enhanced fibroblast migration. NPD8733 specifically binds to valosin-containing protein (VCP)/p97, a member of the ATPase-associated with diverse cellular activities (AAA+) protein family. NPD8733 has the potential for the research of cancer diseases.

VCP/p97 inhibitor-1 is a potent inhibitor of VCP/p97 (also called Cdc48, CDC-. 48, or Ter94) with an IC₅₀ of 54.7 nM. VCP/p97 inhibitor-1 causes the dysregulation of protein homeostasis and disturbs the degradation of misfolded polypeptides by the ubiquitin-proteasome system (UPS).

NW 1028 is a potent VCP/p97 inhibitor. NW 1028 targets the ND1L domain of p97 and inhibits the degradation of a p97-dependent reporter. NW 1028 has good binding affinity with K_d values of 100 and 285 nM for ND1L and full length p97, respectively. NW 1028 has the function of regulating the mitotic spindle of cells.

VCP/p97 IN-2 (Compound V13) is a VCP/p97 inhibitor with IC₅₀ of 32 nM for p97. VCP/p97 IN-2 has excellent antitumor activities and significantly inhibits tumor growth in Molm-13 xenograft mice model. VCP/p97 IN-2 can be used for acute myeloid leukemia (AML) research.

NSC819701 is a triazole inhibitor of the p97 ATPase. NSC819701 inhibits the activity of p97 ATPase by binding to a specific site of p97.