mia paca-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.

Bleomycin Sulfate (Blenoxane) is a glycopeptide antibiotic, an inhibitor of DNA synthesis. Bleomycin Sulfate causes DNA strand breaks but not RNA strand breaks. Bleomycin Sulfate has antitumor activity.

LL-37, Human acetate is a 37-residue, amphipathic, cathelicidin-derived antimicrobial peptide, which exhibits a broad spectrum of antimicrobial activity.

3-Methyladenine (3-MA) is a PI3K inhibitor that selectively inhibits class IB PI3Kγ (IC50 = 60 μM) and class III VPS34 (IC50 = 25 μM). 3-Methyladenine inhibits autophagy.

Royleanone possesses cytotoxic activity against the human pancreatic cancer cell line MIA PaCa-2.

Sodium Oxamate (Oxamic acid sodium salt) is an LDH inhibitor that specifically inhibits LDHA. Sodium Oxamate has antitumor activity and induces cell cycle arrest and apoptosis.

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.

BN82002 (CDC25 Phosphatase Inhibitor I) is a synthetic inhibitor of CDC25 phophatases

Alisertib (MLN 8237) is a specific Aurora A inhibitor (IC50: 1.2 nM). The selectivity of Alisertib(MLN 8237) is >200-fold higher for Aurora A than Aurora B.

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.

LXH254 is a B C RAF inhibitor with IC50 values of 0.2 nM and 0.07 nM for inhibiting BRAF and CRAF.

C75 is an inhibitor synthetic fatty-acid synthase (FASN) and inhibits prostate cancer cells PC3 (IC50: 35 μM).C75 increases CPT1 activity and reduces DIO.

Transketolase-IN-4 is a transketolase inhibitor with an IC50 value of 3.9 μM.Transketolase-IN-4 inhibited Mycobacterium tuberculosis DXS with an IC50 value of 114.1 μM. Transketolase-IN-4 inhibited the SW620, LS174T, and MIA PaCa-2 tumor cell proliferation.

MEK RAF-IN-1 (Compound 16b) serves as an inhibitor targeting both MEK and RAF, demonstrating potent efficacy with IC 50 values reported at 28 nM for MEK1, and 3 nM for both BRAF and BRAFV600E. This compound exhibits significant antitumor capabilities, effectively curbing cell proliferation in vitro in MIA PaCa-2 (G12C KRAS), HCT116 (G13D KRAS), and C26 (G12D KRAS) cells. Furthermore, MEK RAF-IN-1 significantly restricts tumor growth in xenograft mouse models employed in the study of colorectal cancer.

Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0/G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013). Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0/G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3 References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013).

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)

MM41 is a human telomeric and gene promoter DNA quadruplex stabilizer with an IC50 of <10 nM against the MIA PaCa-2 pancreatic cancer cell line.

SB-1295, an orally active CDK9 T1 inhibitor with an IC50 of 0.17 μM, exhibits antiproliferative effects on HCT 116 and MIA PaCa-2 cells. It promotes cell death in MIA PaCa-2 by elevating intracellular ROS levels, diminishing mitochondrial membrane potential, and triggering apoptosis. This compound holds potential for cancer research [1].

MET PDGFRA-IN-1 (compound 8c) is an inhibitor of MET and PDGFRA proteins, with an IC50 of 36 μM against MET. It inhibits MET phosphorylation, induces apoptosis, and reduces proliferation in various MET-positive cell lines, showing IC50 values of 15.3 μM for AsPc-1, 19.0 μM for EBC-1, 22.0 μM for MKN-45, 25.6 μM for Mia-Paca-2, 21.0 μM for HT-29, and 31.5 μM for K562 [1].

SHP2-IN-22, a potent SHP2 allosteric inhibitor, exhibits an IC50 value of 17.7 nM and effectively suppresses proliferation, migration, and invasion in MIA PaCa-2 pancreatic cancer cells. This compound is utilized in the study of Kirsten rat sarcoma viral oncogene (KRAS) mutant cancer research [1].

KRAS inhibitor-14 is a potent inhibitor of KRAS G12C (IC50: 0.249 μM). KRAS inhibitor-14 exhibited p-ERK inhibition in MIA PaCA-2, A549 cells with IC50s of 1.12, >33.3 μM, respectively. KRAS inhibitor-14 has potential to be investigated in pancreatic, colorectal and lung cancers.

Oxythiamine (Hydroxythiamin) is an antivitamin of thiamine and a transketolase (TK) inhibitor. Oxythiamine inhibits cancer cell proliferation and induces cell cycle arrest. Oxythiamine has potential anticancer activity, inhibits non-oxidative synthesis of ribose, and induces apoptosis.

SOS1-IN-17 (Compound 8d) is an orally active inhibitor targeting the SOS1-KRASG12C interaction, with an IC50 of 5.1 nM. It suppresses ERK phosphorylation in DLD-1 cells with an IC50 of 18 nM and demonstrates antiproliferative activity in KRASG12C-mutant Mia-Paca-2 cells, with an IC50 of 0.11 μM. In mouse models, SOS1-IN-17 shows antitumor efficacy against pancreatic cancer.

1-Alaninechalmydocin is a fungal metabolite originally isolated from a Great Lakes-derived Tolypocladium sp. and an inhibitor of histone deacetylases (HDACs). It reduces total HDAC activity in HeLa cell lysates in a concentration-dependent manner. 1-Alaninechlamydocin reduces proliferation of MIA PaCa-2, PANC-1, and hTERT-HPNE cells (GI50s = 5.3, 14, and 2.0 nM, respectively).