Liver Cancer

Rapamycin (Sirolimus; AY 22989) is a potent and specific blood-brain barrier-transmissible mTOR inhibitor with an IC₅₀ of 0.1 nM in HEK293 cells. Rapamycin is a molecular glue that binds FKBP12 and mTOR proteins together, thereby inhibiting mTOR kinase activity. Rapamycin binds to FKBP12 and specifically acts as an allosteric inhibitor of mTORC1. Rapamycin is an autophagy activator, an immunosuppressant.

LY294002 is a broad-spectrum inhibitor of PI3K with IC₅₀s of 0.5, 0.57, and 0.97 μM for PI3Kα, PI3Kδ and PI3Kβ, respectively. LY294002 also inhibits CK2 with an IC₅₀ of 98 nM. LY294002 is a competitive DNA-PK inhibitor that binds reversibly to the kinase domain of DNA-PK with an IC₅₀ of 1.4 μM. LY294002 is an apoptosis activator.

Bortezomib (PS-341) is a reversible and selective proteasome inhibitor, and potently inhibits 20S proteasome (K_i=0.6 nM) by targeting a threonine residue. Bortezomib disrupts the cell cycle, induces apoptosis, and inhibits NF-κB. Bortezomib is the first proteasome inhibitor anticancer agent. Bortezomib can be used for the study of multiple myeloma (MM). Bortezomib effectively inhibits TREM2 expression in tumor-associated macrophages (TAMs).

Metformin (1,1-Dimethylbiguanide) inhibits the mitochondrial respiratory chain in the liver, leading to AMPK activation and enhancing insulin sensitivity, and can be used in the study of type 2 diabetes. Metformin exerts central glucose-lowering effects by inhibiting Ras-related protein 1 (Rap1) in SF1 hypothalamic neurons. Metformin also inhibits liver oxidative stress, nitrosative stress, inflammation, and apoptosis caused by liver ischemia/reperfusion injury. In addition, Metformin regulates the expression of autophagy-related proteins by activating AMPK and inhibiting the mTOR signaling pathway, thereby inducing tumor cell autophagy and inhibiting the growth of renal cell carcinoma in vitro and in vivo.

Trametinib (GSK1120212; JTP-74057) is an orally active MEK inhibitor that inhibits MEK1 and MEK2 with IC₅₀s of about 2 nM. Trametinib activates autophagy and induces apoptosis, cross the blood-brain barrier (BBB), used in research related to subarachnoid hemorrhage (SAH).

Sorafenib (Bay 43-9006) is a potent oral active multikinase inhibitor. Sorafenib blocks autophosphorylation and activity of receptor tyrosine kinases (VEGFR-2, VEGFR-3) and RAF family kinases, thereby suppressing the RAF/MEK/ERK and PI3K/Akt pathways, inhibiting STAT3 phosphorylation, and selectively inhibiting the MAPK pathway in cancer cells. Sorafenib induces cell cycle arrest, autophagy, apoptosis, and PARP cleavage, reduces Bcl-2, Bcl-XL, cyclin D1 levels, and activates Bak and Bax. Sorafenib inhibits tumor growth and metastasis in mouse and rat models. Sorafenib can be used for cancer research, such as colon, breast, non-small-cell lung cancer (NSCLC), ovarian, pancreatic, melanoma, colorectal and hepatocellular carcinoma.

Gefitinib (ZD1839) is a potent, selective and orally active EGFR tyrosine kinase inhibitor with an IC₅₀ of 33 nM. Gefitinib selectively inhibits EGF-stimulated tumor cell growth (IC₅₀ of 54 nM) and that blocks EGF-stimulated EGFR autophosphorylation in tumor cells. Gefitinib also induces autophagy and cell apoptosis, which can be used for cancer related research, such as Lung cancer and breast cancer .

Glycine is an inhibitory neurotransmitter in the CNS and also acts as a co-agonist along with glutamate, facilitating an excitatory potential at the glutaminergic N-methyl-D-aspartic acid (NMDA) receptors. Glycine is orally active. Glycine inhibits the membrane aggregation of NINJ1 and prevents plasma membrane rupture during cell death. Glycine can be used to study cell protection, cancer, neurological diseases, and angiogenesis.

Daraxonrasib (RMC-6236) is an orally active, non-covalent RAS (ON) inhibitor. Daraxonrasib disrupts the interaction of wild-type or mutant RAS proteins with the RAS binding domain of BRAF, with EC₅₀ values ranging from 28-220 nM for wild-type KRAS, NRAS, HRAS, and multiple oncogenic RAS variants. Daraxonrasib inhibits pERK. Daraxonrasib has anti-tumor activity against KRAS mutant tumors.

Ruxolitinib (INCB18424) is an orally active and selective JAK1/2 inhibitor with IC₅₀s of 3.3 nM and 2.8 nM in cell-free assays, and has 130-fold selectivity for JAK1/2 over JAK3. Ruxolitinib induces autophagy and kills tumor cells through toxic mitophagy.

BAY 11-7082 is an IκBα phosphorylation and NF-κB inhibitor. BAY 11-7082 selectively and irreversibly inhibits the TNF-α-induced phosphorylation of IκB-α, and decreases NF-κB and expression of adhesion molecules. BAY 11-7082 inhibits ubiquitin-specific protease USP7 and USP21 (IC₅₀=0.19, 0.96 μM, respectively). BAY 11-7082 inhibits gasdermin D (GSDMD) pore formation in liposomes and inflammasome-mediated pyroptosis and IL-1β secretion in human and mouse cells.

DAPT (GSI-IX) is a potent and orally active γ-secretase inhibitor with IC₅₀s of 115 nM and 200 nM for total amyloid-β (Aβ) and Aβ₄₂, respectively. DAPT inhibits the activation of Notch 1 signaling and induces cell differentiation. DAPT also induces autophagy and apoptosis. DAPT has neuroprotection activity and has the potential for autoimmune and lymphoproliferative diseases, degenerative disease and cancers treatment.

Osimertinib (AZD9291) is a covalent, orally active, irreversible, and mutant-selective EGFR inhibitor with an apparent IC₅₀ of 12 nM against L858R and 1 nM against L858R/T790M, respectively. Osimertinib overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer.

Quercetin, a natural flavonoid, is a stimulator of recombinant SIRT1 and also a PI3K inhibitor with IC₅₀ of 2.4 μM, 3.0 μM and 5.4 μM for PI3K γ, PI3K δ and PI3K β, respectively.

Stattic is a potent STAT3 inhibitor and inhibits STAT3 phosphorylation (at Y705 and S727). Stattic inhibits the binding of a high affinity phosphopeptide for the SH2 domain of STAT3. Stattic ameliorates the renal dysfunction in Alport syndrome (AS) mice.

Trichostatin A (TSA) is a potent and specific inhibitor of HDAC class I/II, with an IC₅₀ value of 1.8 nM for HDAC.

MK-2206 dihydrochloride (MK-2206 2HCl) is an orally active pan-AKT inhibitor, with IC₅₀ values of 8 nM, 12 nM and 65 nM against AKT1, AKT2 and AKT3, respectively. MK-2206 dihydrochloride inhibits the Akt/mTOR signaling pathway and reduces the levels of downstream GSK3β and Mcl-1 via proteasomal degradation. MK-2206 dihydrochloride induces G1-phase cell cycle arrest, apoptosis, epithelial-mesenchymal transition, fibroblast activation and extracellular matrix deposition. MK-2206 dihydrochloride causes transient hyperglycemia and hyperinsulinemia in animals. MK-2206 dihydrochloride can be used in research related to solid tumors, renal fibrosis and hypercholesterolemia.

Nigericin is an antibiotic derived from Streptomyces hygroscopicus that act as a K⁺/H⁺ ionophore, promoting K⁺/H⁺ exchange across mitochondrial membranes. Nigericin is a NLRP3 activator. Nigericin shows promising anti-cancer activities through decreasing intracellular pH (pHi), and inactivation of Wnt/β-catenin signals. Nigericin induces pyroptosis through caspase 1/GSDMD in TNBC.

Verteporfin (CL 318952) is a photosensitizer for photodynamic therapy to eliminate the abnormal blood vessels in the eye associated with conditions such as age-related macular degeneration. Verteporfin is a YAP inhibitor which disrupts YAP-TEAD interactions. Verteporfin induces cell apoptosis. Verteporfinis an autophagy inhibitor that blocks autophagy at an early stage by inhibiting autophagosome formation.

Resveratrol (trans-Resveratrol; SRT501) is a CNS-penetrant natural polyphenolic phytoalexin that possesses anti-oxidant, anti-inflammatory, cardioprotective, and anti-cancer properties. Resveratrol (SRT 501) has a wide spectrum of targets including mTOR, JAK, β-amyloid, Adenylyl cyclase, IKKβ, DNA polymerase. Resveratrol also is a specific SIRT1 activator. Resveratrol is a potent pregnane X receptor (PXR) inhibitor. Resveratrol is an Nrf2 activator, ameliorates aging-related progressive renal injury in mice model. Resveratrol increases production of NO in endothelial cells.