(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 4.2.1.1) 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.