Apoptosis Inducer

Everolimus (RAD001) is a Rapamycin (HY-10219) derivative and a potent, selective, orally active, blood-brain barrier-permeable mTOR1 inhibitor. Everolimus binds to FKBP-12 to generate an immunosuppressive complex. Everolimus inhibits tumor cells proliferation and induces cell apoptosis and autophagy. Everolimus has potent immunosuppressive and anticancer activities.

Capsaicin ((E)-Capsaicin), an active component of chili peppers, is a TRPV1 agonist. Capsaicin induces a nociceptive response by binding to its receptors. Capsaicin has analgesic effects on neurological disorders. Capsaicin has antioxidant, anti-inflammatory, anti-cancer effects.

Anisomycin is a potent protein synthesis inhibitor which interferes with protein and DNA synthesis by inhibiting peptidyl transferase or the 80S ribosome system. Anisomycin is a JNK activator, which increases phospho-JNK. Anisomycin is a bacterial antibiotic.

Alpelisib (BYL-719) is an orally active PI3Kα-selective inhibitor that blocks the conversion of PIP2 to PIP3, thereby inhibiting pathways including PI3K/AKT/mTOR, MAPK/ERK, Notch and JAK-STAT. Alpelisib also induces apoptosis, G0/G1 phase arrest and senescence; it significantly inhibits the proliferation, self-renewal, stemness and epithelial-mesenchymal transition (EMT) of tumor cells, reduces cancer stem cell populations and decreases the expression of stem cell markers. Alpelisib not only enhances the sensitivity to Eribulin (HY-13442) and exerts a synergistic effect with Paclitaxel (HY-B0015), but may also induce drug resistance by upregulating the SGK3/GSK3β/β-catenin signaling pathway. Alpelisib can be applied to research related to breast cancer, gastric cancer and lipomas associated with PTEN hamartoma tumor syndrome.

Simvastatin (MK 733) is a competitive inhibitor of HMG-CoA reductase with a K_i of 0.2 nM.

Valproic acid (VPA) is an orally active HDAC inhibitor, with IC₅₀ in the range of 0.5 and 2 mM. Valproic acid inhibits HDAC1 (IC₅₀, 400 μM), and induces proteasomal degradation of HDAC2. Valproic acid activates Notch1 signaling and inhibits proliferation in small cell lung cancer (SCLC) cells. Valproic acid is used in the epilepsy, bipolar disorder, metabolic disease, HIV infection and prevention of migraine headaches.

Pexidartinib (PLX-3397) is a potent, orally active, selective, and ATP-competitive colony stimulating factor 1 receptor (CSF1R or M-CSFR) and c-Kit inhibitor, with IC₅₀s of 20 and 10 nM, respectively. Pexidartinib (PLX-3397) exhibits 10- to 100-fold selectivity for c-Kit and CSF1R over other related kinases. Pexidartinib (PLX-3397) induces cell apoptosis and has anti-tumor activity. Pexidartinib has limited permeability to the blood-brain barrier, primarily through ABCB1.

STM2457 is a first-in-class, highly potent, selective and orally active METTL3 inhibitor with an IC₅₀ of 16.9 nM. STM2457 can be used for the research of acute myeloid leukaemia (AML).

Oxidopamine (6-OHDA) hydrobromide is an antagonist of the neurotransmitter dopamine. Oxidopamine hydrobromide is a widely used neurotoxin and selectively destroys dopaminergic neurons. Oxidopamine hydrobromide promotes COX-2 activation, leading to PGE₂ synthesis and pro-inflammatory cytokine IL-1β secretion. Oxidopamine hydrobromide can be used for the research of Parkinson’s disease (PD), attention-deficit hyperactivity disorder (ADHD), and Lesch-Nyhan syndrome.

Fludarabine (NSC 118218) is a DNA synthesis inhibitor and a fluorinated purine analogue with antineoplastic activity in lymphoproliferative malignancies. Fludarabine inhibits the cytokine-induced activation of STAT1 and STAT1-dependent gene transcription in normal resting or activated lymphocytes.

(-)-Epigallocatechin Gallate (EGCG) is a major polyphenol in green tea, which can inhibit cell proliferation and induce cell apoptosis. (-)-Epigallocatechin Gallate inhibits glutamate dehydrogenase 1/2 (GDH1/2, GLUD1/2) activity. (-)-Epigallocatechin Gallate has a potent anticancer, antioxidant and anti-inflammatory properties against various types of cancers such as colorectal cancer, myeloid leukemia, thyroid carcinoma.

Camptothecin (CPT), a kind of alkaloid, is a DNA topoisomerase I (Topo I) inhibitor with an IC₅₀ of 679 nM. Camptothecin (CPT) exhibits powerful antineoplastic activity against colorectal, breast, lung and ovarian cancers, modulates hypoxia-inducible factor-1α (HIF-1α) activity by changing microRNAs (miRNA) expression patterns in human cancer cells.

Metronidazole is an orally active nitroimidazole antibiotic. Metronidazole can cross blood brain barrier. Metronidazole can be used for the research of anaerobic infections.

Sulforaphane is an orally active inducer of the Keap1/Nrf2/ARE pathway. Sulforaphane promotes the transcription of tumor-suppressing proteins and effectively inhibits the activity of HDACs. Through the activation of the Keap1/Nrf2/ARE pathway and further induction of HO-1 expression, Sulforaphane protects the heart. Sulforaphane suppresses high glucose-induced pancreatic cancer through AMPK-dependent signal transmission. Sulforaphane exhibits both anticancer and anti-inflammatory properties.

Ro-3306 is a potent and selective inhibitor of CDK1, with K_is of 20 nM, 35 nM and 340 nM for CDK1, CDK1/cyclin B1 and CDK2/cyclin E, respectively.

Trolox is an analogue of vitamin E with a powerful antioxidant effect. Trolox is also a powerful inhibitor of membrane damage.

TAK-243 (MLN7243) is a first-in-class, selective ubiquitin activating enzyme, UAE (UBA1) inhibitor (IC₅₀=1 nM), which blocks ubiquitin conjugation, disrupting monoubiquitin signaling as well as global protein ubiquitination. TAK-243 (MLN7243) induces endoplasmic reticulum (ER) stress, abrogates NF-κB pathway activation and promotes apoptosis.

C646 is a selective and competitive histone acetyltransferase p300 inhibitor with K_i of 400 nM, and is less potent for other acetyltransferases.

Luteolin (Luteoline), a flavanoid compound, is a potent Nrf2 inhibitor. Luteolin has anti-inflammatory, anti-cancer properties, including the induction of apoptosis and cell cycle arrest, and the inhibition of metastasis and angiogenesis, in several cancer cell lines, including human non-small lung cancer cells.

Sodium Butyrate (sodium butanoate) is an inhibitor of HDAC, possessing anti-tumor activity.