ask1

ASK1-IN-1 is an inhibitor of apoptosis signal-regulating kinase 1 which is a key mediator in the apoptotic and inflammatory cellular stress response with an IC50 of 21 nM in biochemica assays.

ASK1-IN-4 is an ASK1 inhibitor, IC50 = 0.2 μM.

ASK1-IN-2 is a potent, orally active inhibitor of apoptosis signal-regulating kinase 1 (ASK1), with an IC50 of 32.8 nM. It has potential therapeutic applications for ulcerative colitis[1].

ASK1-IN-3 is a highly potent and selective inhibitor of ASK1 kinase, demonstrating an IC 50 of 33.8 nM. This compound also exhibits inhibitory effects on various cell cycle regulating kinases. ASK1-IN-3 showcases remarkable induction of apoptosis in HepG2 cancer cells and displays potent activity in arresting the cell cycle [1].

MSC 2032964A is a potent selective ASK1 inhibitor (IC50 = 93 nM) that is oral bioavailable and brain permeable. It inhibited neuroinflammation in mouse EAE models and blocked LPS-induced phosphorylation of ASK1 and p38 in cultured mouse astrocytes.

TC ASK 10 is a potent, selective and orally active inhibitor of apoptosis signal-regulating kinase 1 (ASK1)(IC50 of 14 nM).

ASK120067 is a potent and orally active inhibitor of EGFRT790M (IC50:0.3 nM) with selectivity over EGFRWT (IC50:6.0 nM). ASK120067 is a third-generation EGFR-TKI for the research of non-small cell lung cancer (NSCLC)[1]. In the in vitro kinase assay ASK120067 potently inhibits the EGFR L858R T790M and EGFR T790M resistant mutants with IC50 values of 0.3 nM and 0.5 nM, respectively, as well as the EGFRexon19del sensitizing mutant (IC50= 0.5 nM). The 50 of ASK120067 against wild-type EGFR (EGFRWT) is 6 nM[1].ASK120067 selectively inhibits the growth of EGFR-mutant cell lines and exhibits potent antiproliferative activity in the mutant EGFR NSCLC cells, with IC50 values of 12 nM, 6 nM and 2 nM against NCI-H1975 (T790M mutation), PC-9, and HCC827 cells (sensitizing mutations), respectively. However, it shows moderate or weak anti-growth activities in A431, LoVo and A549 cells (EGFRWT), with IC50 values ranging from 338 nM to 1541 nM[1].ASK120067 (0.1-100 nM) inhibits the phosphorylation of EGFR at Tyrosine residue 1068 and its downstream signaling proteins AKT and ERK in NCI-H1975 cells (EGFRL858R T790M) even at low dosage (0.1-1 nM). Additionally, ASK120067 inhibits p-EGFR and p-Akt and p-erk in EGFR WT A431 cell until the concentration reaches 10 to 100 nM[1]. ASK120067 (oral gavage; 5-20 mg kg; once daily; 21 days) results in significantly regressed tumor growth, with a tumor growth inhibition (TGI) rate of 85.7%, and administration of 10 mg kg ASK120067 causes dramatic tumor shrinkage with a TGI rate of 99.3%, exhibiting a similar potency with Osimertinib[1]. [1]. Tao Zhang, et al. Discovery of a novel third-generation EGFR inhibitor and identification of a potential combination strategy to overcome resistance. Mol Cancer. 2020 May 13;19(1):90.

NQDI-1 (NQDI 1) is a selective inhibitor of apoptosis signal-regulating kinase 1 (ASK1, MAP3K5) (IC50/Ki: 3 μM/500 nM).

Selonsertib (GS-4997) is an orally bioavailable inhibitor of apoptosis signal-regulating kinase 1 (ASK1), with potential anti-inflammatory, antineoplastic and anti-fibrotic activities.

GS-444217 is a selective ATP-competitive inhibitor of apoptosis signal-regulating kinase 1 (ASK1, IC50: 2.87 nM).

(E)-2-(2-Chlorostyryl)-3,5,6-trimethylpyrazine (CSTMP) is a stilbene derivative with antioxidant and anticancer activities. It stimulates proliferation of hydrogen peroxide-damaged ECV-304 cells (EC50 = 24.9 nM). CSTMP reduces hydrogen peroxide-induced release of lactate dehydrogenase (LDH) in and increases viability of human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner via inhibition of apoptosis. It reverses hydrogen peroxide-induced release of malondialdehyde (MDA) and decreases in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities as well as increases constitutive nitric oxide synthase (cNOS) activity and nitric oxide (NO) production in HUVECs. CSTMP also induces cell death of A549 non-small cell lung cancer (NSCLC) cells in an IRE1α-dependent manner through induction of IRE1α-TRAF2-ASK1 complex-mediated endoplasmic reticulum (ER) stress and mitochondrial apoptosis.

Selonsertib, also known as GS-4997, is an orally bioavailable inhibitor of apoptosis signal-regulating kinase 1 (ASK1), with potential anti-inflammatory, antineoplastic and anti-fibrotic activities. GS-4997 targets and binds to the catalytic kinase domain of ASK1 in an ATP-competitive manner, thereby preventing its phosphorylation and activation. GS-4997 prevents the production of inflammatory cytokines, down-regulates the expression of genes involved in fibrosis, suppresses excessive apoptosis and inhibits cellular proliferation.

BPyO-34 is a novel apoptosis signal-regulating kinase 1 (ASK1) inhibitor with IC50 of 0.52μM in vitro in kinase assay.

K812 is an ASK1-specific inhibitor discovered to prolong survival in a mouse model of amyotrophic lateral sclerosis.

Antagonist of 14.3.3 proteins (KD ≈80 nM). Competitively inhibits 14.3.3-ligand interactions without requiring phosphorylation. Blocks the ability of 14.3.3 to bind to target proteins such as Raf-1, Bad, ASK1 and exoenzyme S.

Sulfotanshinone IIA Sodium mitigates oxidative damage in peritoneal mesothelial cells caused by peritoneal dialysis solution (PDS) by inhibiting the ASK1-p38 signaling pathway.

DDO3711, a PP5-recruiting phosphatase recruitment chimera (PHORC), is created by chemically linking an apoptosis signal-regulated kinase 1 (ASK1) inhibitor with a PP5 activator. This compound selectively targets ASK1 (IC50=164.1 nM) over ASK2 (IC50 >20 μM), effectively dephosphorylating p-ASK1 T838 through PP5 recruitment. Exhibiting ASK1-dependent antiproliferative properties, DDO3711 demonstrates anti-cancer activity, making it a promising agent for research into the abnormal phosphorylation of oncoproteins.

K811 is an ASK1-specific inhibitor that prolongs survival in a mouse model of amyotrophic lateral sclerosis. K811 efficiently prevented cell proliferation in cell lines with high ASK1 expression and in HER2-overexpressing GC cells. Treatment with K811 reduced sizes of xenograft tumors by downregulating proliferation markers.