miapaca-2

Adagrasib (MRTX849) is an orally active and selective covalent inhibitor of KRAS G12C. Adagrasib binds to the GDP state of the inactive conformation of KRAS G12C and inhibits KRAS and its downstream signaling. Adagrasib exhibits inhibitory activity against KRAS G12C mutant tumors.

Tributyrin (Glyceryl tributyrate), a neutral short-chain fatty acid triglyceride, is a stable and rapidly absorbed prodrug of Butyric Acid. It diffuses through biological membranes and is metabolized by intracellular lipases, releasing effective butyrate directly into cells in vivo, exhibiting potent proapoptotic, antiproliferative, and differentiation-inducing effects.

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.

HIF-1α-IN-2 is a novel and highly potent HIF-1α inhibitor with anticancer and antitumor activity that inhibits the expression of HIF-1α and VEGF in a dose-dependent manner and inhibits cell migration.

S100A2-p53-IN-1 (compound 51), an inhibitor of S100A2-p53 interactions, targets S100A2, a Ca 2+ binding protein involved in cell signaling and commonly upregulated in pancreatic cancer, and effectively inhibits the growth of the MiaPaCa-2 pancreatic cancer cell line, showing a growth inhibition (GI 50) range of 1.2-3.4 μM [1].

HIF-1α-IN-2 hydrochloride is a potent HIF-1α inhibitor exhibiting anticancer activity, with IC50 values of 28 nM in MDA-MB-231 cells and 15 nM in MiaPaCa-2 cells, effectively suppressing HIF-1α expression by inhibiting transcription and protein translation [1].

ATR-IN-22 (Compound 34), an orally active ATR inhibitor, exhibits potent anti-proliferative effects on MIAPaCa-2 cells with an IC50 value of less than 1 μM and demonstrates anti-tumor activity in colon cancer [1].

HIF-1α-IN-6 (compound 3s) is a potent inhibitor of HIF-1α with IC50 values of 0.6 nM and 53.3 nM in MiaPaCa-2 and MDA-MB-231 cells, respectively, and it suppresses HIF-1α expression by reducing HIF-1α mRNA levels [1].

2-(Cyclohexylmethyl)-Plumbagin, a naphthoquinone derivative, exhibits selective cytotoxicity towards PANC-1 human pancreatic cancer cells under nutrient-deprived conditions—a situation akin to the pancreatic cancer tumor microenvironment—over those in nutrient-rich settings, with PC50 values of 0.11 and 47.2 µM, respectively. At a 1 µM concentration, it triggers apoptosis in PANC-1 cells. Furthermore, this compound specifically inhibits the phosphorylation of Akt and mammalian target of rapamycin (mTOR) in PANC-1 cells under nutrient scarcity. In a MiaPaCa-2 pancreatic cancer mouse xenograft model, it significantly reduces tumor volume and weight when administered at 50 and 250 µg/animal dosages five times weekly.