p97

ML241 is a potent and selective inhibitors of p97 ATPase.ML241 inhibits degradation of a p97-dependent but not a p97-independent proteasome substrate in a dual-reporter cell line. ML241 may be a novel agent for the chemotherapy of cancer, and provide a rationale for developing pathway-specific p97 inhibitors.

MNS is a tyrosine kinases inhibitor, inhibits Syk, Src, p97 with IC50 of 2.5 μM, 29.3 μM and 1.7 μM, respectively.

MSC1094308 is a reversible, non-ATP-competitive alterative inhibitor targeting type II AAA ATPase (VCP/p97) and type I AAA ATPase (VPS4B), which affects the intracellular protein degradation process by binding to a specific hotspot region of p97 and inhibiting D2 ATPase activity.

NMS-873 is a potent and selective allosteric inhibitor of VCP/p97.

DBEQ (JRF 12) is a selective, potent, reversible, and ATP-competitive p97 inhibitor.

ML241 is a potent and selective inhibitors of p97 ATPase.

ML240 is a selective, ATP-competitive p97 inhibitor.

VCP/p97 inhibitor-1, a highly effective compound, inhibits VCP/p97 (also known as Cdc48, CDC-48, or Ter94) with an IC 50 of 54.7 nM. This inhibitor induces a disruption in protein homeostasis and interferes with the degradation process of misfolded polypeptides by the ubiquitin-proteasome system (UPS).

p97-IN-1 is a potent inhibitor of p97 with an IC 50 <30 nM [1].

CB-5083 is a potent, selective, and orally bioavailable p97 AAA ATPase inhibitor ( IC50=11 nM).

NPD8733 is an inhibitor of cancer cell-enhanced fibroblast migration, specifically binding to valosin-containing protein (VCP)/p97.

WHI-P97 HCl is a potent and selective JAK-3 inhibitor. WHI-P97 had an estimated Ki value of 0.09 microM from modeling studies and a measured IC50 value of 2.5 microM in EGFR kinase inhibition assays. WHI-P97 effectively inhibited the in vitro invasiveness of EGFR-positive human cancer cells in a concentration-dependent manner.

WHI-P97 is a rationally designed potent inhibitor of JAK-3. IC50 value: Target: JAK3 Treatment of mast cells with WHI-P97 inhibited the translocation of 5-lipoxygenase (5-LO) from the nucleoplasm to the nuclear membrane and consequently 5-LO-dependent leukotriene (LT) synthesis after IgE receptor/FcepsilonRI crosslinking by >90% at low micromolar concentrations. WHI-P97 did not directly inhibit the enzymatic activity of 5-LO, but prevented its translocation to the nuclear membrane without affecting the requisite calcium signal.

UPCDC30245 is an AAA ATPase p97 allosteric inhibitor.

NMS-859 is an effective and covalent inhibitor of valosin-containing protein (VCP)/p97 with IC50s of 0.37 μM and 0.36 μM for wild-type VCP in the presence of 60 μM and 1 mM ATP in cells, respectively.

Eeyarestatin I is an inhibitor that inhibits the degradation and translocation of ER-associated proteins. Eeyarestatin I is associated with the p97 deubiquitination process and inhibits atx3 deubiquitination. Eeyarestatin I has anticancer effects by inducing proteins that cause cell death.

NW 1028 is a potent inhibitor of VCP/p97. NW 1028 selectively acts on the ND1L domain of p97 and inhibits the degradation of p97-dependent reporter genes. NW 1028 has a regulatory effect on the mitotic spindle.

UPCDC30766, a potent allosteric inhibitor of p97, exhibits an IC50 of 12 nM and is applicable for colon cancer research [1].

UP12 enhances ATPase activity by activating valosin-containing protein (VCP), with an EC50 of 2.57 μM.

UP163 enhances ATPase activity and activates valosin-containing protein (VCP), with an EC50 of 9.0 μM. It also reduces MG-132-induced TDP-43 aggregation.

UP158 enhances ATPase activity and stimulates valosin-containing protein (VCP), with an EC50 of 2.57 μM.

NSC799462, a triazole inhibitor, specifically targets p97 ATPase, exerting its effect by binding to a designated site on the p97 enzyme. This interaction induces localized structural alterations in p97, effectively inhibiting its ATPase activity with an IC 50 value of 15 nM.

NSC819701 is a triazole-based inhibitor of p97ATPase. It inhibits the activity of p97ATPase by binding to specific sites on p97.

KUS121 is a valosin-containing protein (VCP) modulator that inhibits VCP ATPase activity (IC50= 330 nM).1It inhibits cell death, ATP depletion, and upregulation of C/EBP-homologous protein (CHOP) induced by tunicamycin, an inducer of ER stress, in HeLa cells when used at concentrations of 20, 50, and 50 μM, respectively. KUS121 (100 μM) inhibits ATP depletion and cell death induced by oxygen-glucose deprivation (OGD) in rat primary cortical neurons in anin vitromodel of cerebral ischemia.2It reduces infarction volume and increases the latency to fall in an accelerating rotarod test in a mouse model of focal cerebral ischemia induced by transient distal middle cerebral artery occlusion (MCAO) when administered at a dose of 100 mg/kg immediately following occlusion and again at 50 mg/kg following reperfusion. KUS121 (50 mg/kg) inhibits thinning of the retinal outer nuclear layer and preserves visual function in an rd10 mouse model of retinitis pigmentosa.1 1.Ikeda, H.O., Sasaoka, N., Koike, M., et al.Novel VCP modulators mitigate major pathologies of rd10, a mouse model of retinitis pigmentosaSci. Rep.45970(2014) 2.Kinoshita, H., Maki, T., Yasuda, K., et al.KUS121, a valosin-containing protein modulator, attenuates ischemic stroke via preventing ATP depletionSci. Rep.9(1)11519(2019)