Avotaciclib is a novel cyclin-dependent kinase inhibitor,exhibited inhibitory activities against CDK1​/cyclinB, CDK2​/cyclinE, CDK4​/cyclinD, CDK5​/p25 and CDK6​/cyclinD with IC50 values of 1.5 nM , 1.5 nM, 854.5 nM, 2.4 nM and >220 nM, resp.

A potent γ-secretase inhibitor with IC50 of 0.4 nM, inhibition of Aβ secretion from SH-SY5Y SPA4CT cells; inhibits the γ-secretase-mediated cleavage of the Notch receptor, reduces tumor cell proliferation, inhibits serum independence, and induces apoptosis in vitro and in vivo using mouse xenograft models.

Saridegib (Patidegib, IPI-926) is a potent and orally active Hedgehog (Hh) pathway antagonist with IC50 of 7 nM; binds to and inhibits the cell membrane-spanning G-protein coupled receptor SMO; demonstrates improved pharmaceutical properties and potency and a favorable pharmacokinetic profile relative to cyclopamine and IPI-269609; completely suppresses tumor growth in a Hh-dependent medulloblastoma allograft model.

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.

A potent and selective HSP90 inhibitor with IC50 of 21 and 7.8 nM for HSP90β and HSP90α, respectively; weakly inhibits HSP90 family members GRP94 and TRAP-1 (Ki=108 and 53 nM), shows no inhibition of HSP72 ATPase and little or no activity against a range of 13 kinases; inhibits proliferation of human tumor cells (GI50=2-40 nM), induces G(1)-G(2) arrest and apoptosis; exhibits in vivo activity against xenograft tumor growth, angiogenesis and metastasis.

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.

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).

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.

(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.

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.