bxpc-3

Gemcitabine (LY188011) is a synthetic cytosine nucleoside derivative and an inhibitor of DNA synthesis. Gemcitabine has antitumor and antimetabolic activities. Gemcitabine induces autophagy and apoptosis.

(-)-Epigallocatechin Gallate (EGCG) is a phenolic antioxidant polyphenol flavonoid found in plants such as green and black tea, which inhibits telomerase and DNA methyltransferase, blocks the activation of EGF receptors and HER-2 receptors, inhibits cellular oxidation, and prevents free radical damage to cells.

Defactinib (VS-6063) is a second-generation inhibitor of FAK that inhibits FAK phosphorylation at the Tyr397 site. Defactinib has potential antitumor activity.

SKLB-163 acts by downregulating RhoGDI, activating JNK-1 signaling pathway and caspase-3, and reducing phosphorylated Akt and p44 42 MAPK.

Datopotamab deruxtecan (DS-1062) is a trophoblast cell surface antigen 2 (TROP2)-targeted antibody-drug conjugate (ADC) with antitumor activity. Datopotamab deruxtecan induces significant antibody-dependent cellular cytotoxicity in the presence of peripheral blood lymphocytes and inhibits tumor growth in xenograft models.

HM90822 is a novel synthetic apoptotic protein (IAP) antagonist that induces apoptosis in human pancreatic cancer cells through proteasome-dependent degradation of IAPs containing the BIR2 3 structural domain.HM90822 inhibits the expression of XIAP and cIAP1 2 proteins in HM822-sensitive Panc-1 and BxPC-3 cells, induces ubiquitylation of IAPs and promotes induces IAP ubiquitination and promotes proteasome-dependent IAP degradation.

Triacetylresveratrol (Acetyl-trans-resveratrol) has anti-cancer activity,it inhibits the phosphorylation of STAT3 and NFκB, down-regulates Mcl-1, and up-regulates Bim and Puma in pancreatic cancer cells.

Gemcitabine hydrochloride (LY 188011 hydrochloride) is a synthetic cytosine nucleoside derivative and an inhibitor of DNA synthesis. Gemcitabine has antitumor and antimetabolic activities. Gemcitabine induces autophagy and apoptosis.

LB100 (LB-100) is a water soluble protein phosphatase 2A (PP2A) inhibitor.

TEPP-46 (ML265) is an activator of pyruvate kinase M2 (PKM2) (AC50=92 nM), selective for PKM1, PKL and PKR. TEPP-46 has antitumor activity.

Chromomycin A3 is an antibiotic produced by Streptomyces sp that binds to gc-rich DNA sequences in the presence of divalent cations and inhibits DNA replication and transcription; it is also used as a fluorescent DNA stain and assay; and it has anticancer activity against diseases such as Hodgkin's, lung adenocarcinomas, melanomas, and breast cancer.

Mahanimbine is found in the roots, leaves and stems of Murraya koenigii and is an orally active alkaloid extracted from Murraya koenigii. Bifidobacterium bifidum leaves on histopathological changes in pancreatic beta cells of streptozotocin-induced diabetic rats.

Nampt-IN-15 (Example 3) is a Nampt inhibitor that exhibits cytotoxic effects on various cell lines, including BxPC-3, HepG2, L540cy, and MOLM-13. The respective IC50 values for these cell lines are 38.5 nM, 8 nM, 8.5 nM, and 7 nM.

TRAP-1 (XJZ-06-462) is a p53 transcription activator that effectively activates mutant p53 and triggers the transcription of p53 target genes. In the p53Y220C pancreatic cell line, TRAP-1 rapidly upregulates p21 and other p53 target genes. TRAP-1 also inhibits cell proliferation, exhibiting IC50 values of 3.94 μM and 0.531 μM in BxPC-3 and A549 cell lines, respectively. Additionally, TRAP-1 modulates autophagy in lung cancer cells and provides protection against oxidative stress and apoptosis.

AXL Angiokinase-IN-1 (compound 11b) is an inhibitor of AXL triple angiokinase, with an IC50 of 3.75 nM for AXL expression. This compound suppresses epithelial-mesenchymal transition (EMT) in Bxpc-3 cells and prevents metastasis in lung cancer cells. Additionally, AXL Angiokinase-IN-1 impairs the functions of vascular and fibroblast cells and induces apoptosis in both cancer and fibroblast cells. It is characterized by low toxicity and favorable metabolic stability.

Amsilarotene (TAC101) inhibits the phosphorylation of retinoblastoma gene product (RB) and increases the presence of 2 cyclin-dependent kinases (CDK) inhibitors resulting in cell cycle arrest. This agent also causes a cytotoxic decline in the thymidylate synthase and cyclin A expression.

QD-394 is an inducer of reactive oxygen species (ROS) production.1It induces lipid peroxidation, increases in intracellular accumulation of reactive oxygen species (ROS), and decreases in the reduced glutathione (GSH) to oxidized GSH (GSSG) ratio in MIA PaCa-2 pancreatic cancer cells when used at concentrations ranging from 0.5 to 10 μM. QD-394 is cytotoxic to MIA PaCa-2, PANC-1, and BxPC-3 cancer cells (IC50s = 0.64, 0.34, and 0.9 μM, respectively). QD-394 acts synergistically with napabucasin to reduce colony formation in MIA PaCa-2 cells. 1.Hu, S., Sechi, M., Singh, P.K., et al.A novel redox modulator induces a GPX4-mediated cell death that is dependent on iron and reactive oxygen speciesJ. Med. Chem.63(17)9838-9855(2020)

CAY10760 is an inhibitor of the protein-protein interaction between RAD51 recombinase and BRCA2 (EC50= 19 μM in a cell-free competitive ELISA).1It decreases homologous recombination by 54% in wild-typeBRCA2-expressing BxPC-3 pancreatic cancer cells when used at a concentration of 20 μM. CAY10760 (20 μM) decreases proliferation of BxPC-3, as well as mutantBRCA2-expressing Capan-1, cancer cells when used alone or in combination with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib . 1.Bagnolini, G., Milano, D., Manerba, M., et al.Synthetic lethality in pancreatic cancer: Discovery of a new RAD51-BRCA2 small molecule disruptor that inhibits homologous recombination and synergizes with olaparibJ. Med. Chem.63(5)2588-2619(2020)

GM 1489 is a broad-spectrum inhibitor of matrix metalloproteinases (MMPs) with Ki values of 0.002, 0.1, 0.5, 0.2, and 20 μM for MMP-1, MMP-8, MMP-2, MMP-9, and MMP-3, respectively. It reduces 5-aza-2'-deoxycytidine-induced increases in MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, and MMP-14 expression as well as cell invasion in AsPC-1, BxPC-3, Hs766T, MiaPaCa2, and PANC-1 cancer cells. Topical administration of GM 1489 (100 μg) inhibits increases in ear thickness and epidermal hyperplasia induced by phorbol 12-myristate 13-acetate and phorbol dibutyrate (PdiBu) in mice.

Steviolbioside (CCRIS-6025) is a natural sweetener, it presents notable inhibition on human hepatocarcinoma cell Hep3B, human breast cancer cell MDA-MB-231 and human pancreatic cancer cell BxPC-3, thus, steviolbioside(CCRIS-6025) could be a potential remedy for human breast cancer. Steviolbioside exhibits moderate antituberculosis activity against M. tuberculosis strain H37RV in vitro.

Microtubule inhibitor 6 (compound 17o) is a potent microtubule inhibitor exhibiting cytotoxicity against NCI-H460, BxPC-3, and HT-29 cells, with IC50 values of 14.0, 6.6, and 7.0 nM, respectively. It effectively inhibits microtubule polymerization.

Microtubule inhibitor 4 (compound 2) is a potent microtubule inhibitor that prevents microtubule protein polymerization and exhibits cytotoxicity in HT-29 cells (IC50: 2.1 nM).

OXPHOS-IN-1 (compound 2) is an inhibitor of oxidative phosphorylation (OXPHOS) that inhibits the growth of MIA PaCa-2 cells (IC50: 2.34 μM) and BxPC-3 cells (IC50: 13.82 μM).

Ki16198 is an orally available LPA receptor antagonist and is a methyl ester derivative of Ki16425. It inhibits LPA1- and LPA3-induced inositol phosphates with Ki values of 0.34 and 0.93 μM, respectively, and can be used in studies of pancreatic carcinogenesis and metastasis.