Pancreatic cancer, or cancer of the pancreas, is one of the more dangerous forms of cancer.Diabetes is listed as a risk factor and also a potential consequence of pancreatic cancer.
The pancreas is an organ that sits close behind the stomach and plays an important part in digestion as well as in keeping our blood sugar levels at safe levels.
Pancreatic cancer is when cells start being produced in the pancreas in an uncontrolled fashion by the body. This can lead to a number of health risks which can include diabetes in some cases.
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(R)-GNE-140 (GNE-140) is a novel potent, selective lactate dehydrogenase (LDH) inhibitor with IC50 of 3, 5, and 5 nM for LDHA, LDHB, and LDHC, respectively; displays no inhibition on malate MDH-1, MDH-2 (IC50>10 uM for both enzymes), and no appreciable inhibition against a panel of 301 kinases (<50% inhibition at 1 uM); perturbs glycolysis and inhibits proliferation in MIA PaCa-2 cells (IC50=0.43 uM), decreases glucose uptake (IC50=0.47 uM); pancreatic cell lines that utilize oxidative OXPHOS rather than glycolysis are inherently resistant to GNE-140, which can be resensitized to GNE-140 with the OXPHOS inhibitor phenformin.
The racemate of GNE-140, a novel potent, selective lactate dehydrogenase (LDH) inhibitor with IC50 of 3, 5, and 5 nM for LDHA, LDHB, and LDHC, respectively; displays no inhibition on malate MDH-1, MDH-2 (IC50>10 uM for both enzymes), and no appreciable inhibition against a panel of 301 kinases (<50% inhibition at 1 uM); perturbs glycolysis and inhibits proliferation in MIA PaCa-2 cells (IC50=0.43 uM), decreases glucose uptake (IC50=0.47 uM); pancreatic cell lines that utilize oxidative OXPHOS rather than glycolysis are inherently resistant to GNE-140, which can be resensitized to GNE-140 with the OXPHOS inhibitor phenformin.
Minnelide is a water-soluble prodrug of triptolide that is highly effective in reducing pancreatic tumor growth and spread, and improving survival; efficiently downregulates both CD133(-) and CD133(+) population in the tumors, resulting in a 60% decrease in tumor volume; also is very effective as a therapeutic option against Castration Resistant Prostate Cancer (CRPC)
GSK-2256098 (GTPL-7939) is a potent, selective, reversible and ATP-competitive inhibitor of FAK kinase with Ki of 0.4 nM; dispalys high selectivity over a panel of 261 kinases, including the nearest FAK family member, Pyk2 (>1,000-fold); inhibits FAK activity through targeting the phosphorylation site of FAK Y397; decreases levels of phosphorylated Akt and ERK, cell viability, anchorage-independent growth, and motility in L3.6P1 cells; causes lower microvessel density, less cellular proliferation, and higher apoptosis rates in the Ishikawa model.
SLC-0111 is a sulfonamide carbonic anhydrase (CA, EC 188.8.131.52) inhibitor with IC50 of 45 nM and 4.5 nM for tumor-associated enzymes hCA IX and hCA XII; showed selective CA IX/XII inhibitory profiles, displays >20-fold and >100-fold selectivity over hCA II and hCA I, respectively; reduces tumor cell growth and increases apoptotic cell death in prostate cancer cells.
PF-4136309 (INCB8761) is a potent, selective, competitive, reversible full CCR2 antagonist with IC50 of 2-5 nM; depletes inflammatory monocytes and macrophages from the primary tumor and premetastatic liver resulting in enhanced antitumor immunity, decreased tumor growth, and reduced metastasis.
AZD 5069 (AZD5069) is a potent, selective, slowly reversible and orally bioavailable CXCR2 antagonist that inhibits CXCL8 binding to CXCR2 with pIC50 of 9.1; weakly inhibits CXCL8 binding to CXCR1 with pIC50<7, and no affinity for CCR2 and CCR5; inhibits neutrophil chemotaxis with pA2 of 9.6, and adhesion molecule expression of 6.9, in response to CXCL1; demonstrates potential activity in acute LPS-induced lung inflammation models.
A gemcitabine phosphoramidate prodrug that can overcome the key cancer resistance; NUC-1031 is significantly less dependent on deoxycytidine kinase and on nucleoside transporters, and it is resistant to cytidine deaminase-mediated degradation compared with gemcitabine; inhibits L1210 and BxPC-3 cell proliferation with IC50 of 35 nM and 150 nM, respectively; significantly reduces tumor volumes in vivo in pancreatic cancer xenografts.
The active diterpene in the traditional Chinese medicine Lei Gong Teng, induces Ca(2+) release by a polycystin-2 (PC2)-dependent mechanism; arrests cellular proliferation and attenuates overall cyst formation by restoring Ca(2+) signaling in a murine model of ADPKD; also covalently binds to human XPB (ERCC3), a subunit of the transcription factor TFIIH, and inhibits its DNA-dependent ATPase activity, which leads to the inhibition of RNA polymerase II-mediated transcription; inhibits TAK1 kinase activity by interfering with the formation of the TAK1-TAB1 complex in macrophages.
Evofosfamide is a potent and selective hypoxia-activated phosphoramidate DNA cross-linking mustard; selectively potent under hypoxia and stable to liver microsomes; inhibits H246 cells and HT29 cells with IC50 of 0.1 uM and 0.2 uM respectively; active in an in vivo MIA PaCa-2 pancreatic cancer orthotopic xenograft model.
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