pdac

Almorexant (ACT 078573) is a potent and competitive dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist with Ki values of 1.3 and 0.17 nM for OX1 and OX2, respectively.

Almorexant hydrochloride (ACT 078573 hydrochloride) is an orally active dual orexin receptor antagonist that blocks the intracellular Ca2+ signaling pathway and, to a certain extent, blocks the excitatory effects of methamphetamine. Almorexant hydrochloride Induces apoptosis and can be used to study sleep disorders.

Telaglenastat (CB 839) (IC50 of 24 nM), an effective, specific, and oral inhibitor, which is bioavailable glutaminase, for recombinant human GAC.

DCLK1-IN-1 is a selective, in vivo compatible chemical probe of the kinase domain of doublecortin-like kinase 1 (DCLK1) and a highly selective DCLK1/2 inhibitor with IC50 values ​​of 9.5/57.2 nM (DCLK1) and 31/103 nM (DCLK2) by binding and kinase assays, respectively. It has low toxicity and is used to study DCLK1 biology and determine its role in cancer.

GOT1 inhibitor-1 (GOT1 inhibitor 2c) is a novel, potent and non-covalent inhibitor of glutamate oxaloacetate transaminase 1 (GOT1) with an IC50 of 8.2 uM.

ZZW-115 hydrochloride inhibits the activity of NUPR1.

AOH1996 is an orally active ligand for the replicasome component PCNA (proliferating cell nuclear antigen), targeting the transcription-replication conflict (TRC). It interferes with the interaction of PCNA with its binding proteins, leading to DNA replication stress and apoptosis. AOH1996 causes proteasome-dependent rpb1 degradation and lethal DNA damage by stabilizing the interaction between PCNA and RNA polymerase II, and acts synergistically with DNA damaging agents to inhibit tumor cell growth.

AZD0022 is a selective, reversible, and orally active KRAS G12D inhibitor exhibiting high affinity for both active (KRAS G12D-GTP) and inactive (KRAS G12D-GDP) proteins, whilst demonstrating selectivity for wild-type KRAS. AZD0022 exhibits tumour marker inhibition in PDAC and NSCLC models, making it suitable for investigating tumours such as advanced solid tumours, pancreatic cancer, and colorectal cancer.

RMC5127 is an orally available, mutation-selective RAS G12V inhibitor exhibiting central nervous system (CNS) and brain permeability. It suppresses the RAS pathway and induces apoptosis in KRAS G12V mutant cancer cells, demonstrating antitumour activity.

Brigimadlin (BI 907828) is an orally active and highly potent E3 ubiquitin-protein ligase MDM2-p53 antagonist with antitumor activity.Brigimadlin can be used to study metastatic BTC, PDAC, lung adenocarcinoma, or bladder cancer.

GAC0003A4 is a potent LXR inverse agonist with antitumor activity that inhibits the transcription of LXR proteins.GAC0003A4 degrades LXRβ proteins and inhibits the proliferation of PDAC cells in a dose-dependent manner.GAC0003A4 has been used in the study of advanced pancreatic cancers and other recalcitrant malignancies.

EN460 is a selective inhibitor of Endoplasmic Reticulum Oxidase 1 (ERO1α), inhibiting ERO1L-mediated gene silencing and cell migration, and PDAC invasion.

FAK-IN-22 (Compound 26) is an inhibitor of FAK, JAK3, and Aurora B, with IC50 values of 50.94 nM, 9.99 nM, and 0.49 nM, respectively, effectively suppressing tumorigenesis and metastasis in pancreatic ductal adenocarcinoma (PDAC). It inhibits proliferation in PANC-1 cells with an IC50 of 0.15 μM. FAK-IN-22 induces apoptosis and G2/M phase arrest in PANC-1 cells by inhibiting the FAK/PI3K/Akt signaling pathway.

ROCK/HDAC-IN-2 (Compound C-9) is a dual inhibitor of ROCK/HDAC, characterized by IC50 values of 0.185 µM for HDAC6, 0.8 µM for ROCK1, and 0.7 µM for ROCK2. It effectively induces apoptosis and mitochondrial membrane potential alterations in cancer cells and demonstrates notable antitumor activity, making it useful for research in pancreatic ductal adenocarcinoma (PDAC) and triple-negative breast cancer (TNBC).

LIB3S0280 is a potent inhibitor of TBK1, with an IC50 of 493.9 nM. It suppresses TBK1 downstream signaling by reducing the phosphorylation of IκBα and AKT. LIB3S0280 causes G2/M phase arrest and induces apoptosis in pancreatic cancer cells. Notably, it exhibits significant inhibitory effects on pancreatic cancer cell lines with high TBK1 expression, with a 96-hour IC50 value ranging from 6.64-10.98 μM. LIB3S0280 shows potential for research in pancreatic ductal adenocarcinoma (PDAC).

Antitumor agent-165 (Compound 10l) is an effective inhibitor of focal adhesion kinase (FAK). It exhibits significant antiproliferative effects against CAPAN-1, PANC-1, PATU-T, SUIT-2, BxPC-3, PDAC-3, and PANC-1 GR cell lines, with IC50 values ranging from 1.04 to 3.44 μM.

JWJ-01-306 is a molecular glue that targets the C2H2 zinc finger transcription factor ZBTB11. It effectively degrades ZBTB11, reduces oxidative phosphorylation (OXPHOS) and the tricarboxylic acid (TCA) cycle, and inhibits the proliferation of KAS-resistant PDAC cells. In mouse models, JWJ-01-306 demonstrates favorable pharmacokinetic properties.

CIDD-8633 is a potent inhibitor of DDR2 with an IC50 of 6.105 μM. It significantly suppresses the proliferation of MIA-PaCa-2 and AsPC-1 cells, with IC25 values of 4.0 and 5.5 μM, respectively. Additionally, CIDD-8633 hinders cell migration, arrests the cell cycle, induces apoptosis (apoptosis), and substantially reduces the growth of pancreatic ductal adenocarcinoma (PDAC) tumors. This compound is applicable in pancreatic cancer research, including studies on PDAC.

KRASG12D-IN-7 is a selective inhibitor of KRASG12D. It exhibits strong binding affinity to KRASG12D in both GDP-bound and GTP-bound states, with Kd values of 1.12 nM and 1.86 nM, respectively. This compound inhibits the proliferation of KRASG12D-bearing AsPC-1 cells with an IC50 of 10 nM and disrupts MAPK signaling. In AsPC-1 cells, KRASG12D-IN-7 induces G0/G1 phase arrest and apoptosis (apoptosis), and significantly suppresses colony formation. The inhibitor is applicable for research on cancers with KRASG12D mutations, particularly pancreatic ductal adenocarcinoma (PDAC).

5-Methyl cromolyn (C5OH) disodium is a cromolyn analog that acts as an S100P inhibitor. It prevents the interaction between S100P and its receptor RAGE, hinders NF-κB activity and cell proliferation, and enhances apoptosis induced by Gemcitabine. In murine models with PDAC, 5-Methyl cromolyn disodium reduces tumor growth and metastasis, thereby extending survival. This compound is suitable for pancreatic cancer research, including studies on pancreatic ductal adenocarcinoma (PDAC).

MMRi62 (7-[(2,3-dichlorophenyl)-(pyridin-2-ylamino)methyl]quinolin-8-ol), a ferroptosis inducer targeting MDM2-MDM4 (negative regulators of tumor suppressor p53). MMRi62 shows a P53-independent pro-apoptotic activity against pancreatic ductal adenocarcinoma (PDAC) cells and induce autophagy. MMRi62 inducesferroptosis, resulting in a increase of reactive oxygen and lysosomal degradation of ferritin heavy chain (FTH1). MMRi62 also leads to proteasomal degradation of mutant p53, also inhibits orthotopic xenograft PDAC mouse model in vivo with high frequency mutation characteristics of KRAS and TP53.12.

XP-524 is a potent inhibitor of BET and EP300. XP-524 has significant tumouricidal effects in vivo, preventing KRAS-induced tumour transformation in vivo and prolonging survival in two aggressive PDAC transgenic mouse models. XP-524 also enhances the expression of its own peptide and recruitment of tumour cells to cytotoxic T lymphocytes. XP-524 has shown potential for research in pancreatic ductal adenocarcinoma (PDAC).

UNC10112785 is a novel potent inhibitor of CDK8, CDK19, and CDK9 with IC50 at 1.05, 2.67, and 19.9 nM, respectively, causing MYC loss through both transcriptional and posttranslational mechanisms, and suppressing PDAC anchorage-dependent and anchorage-independent growth, inducing the substantial loss of MYC protein in both two-dimensional (2D) and 3D cell cultures.

Aspulvinone H is a natural inhibitor of glutamic oxaloacetate transaminase 1 (GOT1), suppressing glutamine metabolism, making PDAC cells sensitive to oxidative stress and inhibiting cell proliferation, exhibiting potent in vivo antitumor activity in an SW1990-cell-induced xenograft model.