Leukemia/Lymphoma/Myeloma

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.

5-Fluorouracil (5-FU) is an analogue of uracil and a potent antitumor agent. 5-Fluorouracil affects pyrimidine synthesis by inhibiting thymidylate synthetase thus depleting intracellular dTTP pools. 5-Fluorouracil induces apoptosis and can be used as a chemical sensitizer. 5-Fluorouracil also inhibits HIV.

Venetoclax (ABT-199; GDC-0199) is a highly potent, selective and orally bioavailable Bcl-2 inhibitor with a K_i of less than 0.01 nM. Venetoclax induces autophagy.

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).

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.

Tazemetostat (EPZ-6438) is a potent, selective and orally available EZH2 inhibitor. Tazemetostat inhibits the activity of human polycomb repressive complex 2 (PRC2)-containing wild-type EZH2 with a K_i value of 2.5 nM. Tazemetostat inhibits EZH2 with IC₅₀s of 11 and 16 nM in peptide assay and nucleosome assay, respectively. Tazemetostat inhibits rat EZH2 with an IC₅₀ of 4 nM. Tazemetostat also inhibits EZH1 with an IC₅₀ of 392 nM. Tazemetostat induces apoptosis and differentiation specifically in SMARCB1-deleted MRT cells.

Lenvatinib (E7080) is an oral, multi-targeted tyrosine kinase inhibitor that inhibits VEGFR1-3, FGFR1-4, PDGFR, KIT, and RET, shows potent antitumor activities.

Etoposide (VP-16; VP-16-213) is an anti-cancer chemotherapy agent. Etoposide inhibits topoisomerase II, thus stopping DNA replication. Etoposide induces cell cycle arrest, apoptosis and autophagy.

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.

Gemcitabine (LY 188011) is a pyrimidine nucleoside analog antimetabolite and an antineoplastic agent. Gemcitabine inhibits DNA synthesis and repair, and can modulate autophagy. Gemcitabine induces apoptosis through the activation of p38 MAPK. Gemcitabine demonstrates efficacy in mouse models of pancreatic and breast cancer. Gemcitabine can be used for cancer research, such as pancreatic cancer, non-small cell lung cancer, and breast cancer.

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.

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.

Dasatinib (BMS-354825) is a highly potent, ATP competitive, orally active dual Src/Bcr-Abl inhibitor with potent antitumor activity. The K_is are 16 pM and 30 pM for Src and Bcr-Abl, respectively. Dasatinib inhibits Bcr-Abl and Src with IC₅₀s of <1.0 nM and 0.5 nM, respectively. Dasatinib also induces apoptosis and autophagy, and can cross the blood-brain barrier.

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.

Decitabine (NSC 127716) is an orally active deoxycytidine analogue antimetabolite and DNA methyltransferase inhibitor. Decitabine incorporates into DNA in place of cytosine can covalently trap DNA methyltransferase to DNA causing irreversible inhibition of the enzyme. Decitabine induces cell G2/M arrest and cell Apoptosis. Decitabine has potent anticancer activity.

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.