Apoptosis Inducer

Birinapant (TL32711), a bivalent Smac mimetic, is a potent antagonist for XIAP and cIAP1 with K_ds of 45 nM and less than 1 nM, respectively. Birinapant (TL32711) induces the autoubiquitylation and proteasomal degradation of cIAP1 and cIAP2 in intact cells, which results in formation of a RIPK1: caspase-8 complex, caspase-8 activation, and induction of tumor cell death. Birinapant (TL32711) targets TRAF2-associated cIAPs and abrogates TNF-induced NF-κB activation.

FX-11 is a potent, selective, reversible and competitive lactate dehydrogenase A (LDHA) inhibitor, with a K_i of 8 μM. FX-11 reduces ATP levels and induces oxidative stress, ROS production and cell death. FX-11 shows antitumor activity in lymphoma and pancreatic cancer xenografts.

Daunorubicin (Daunomycin) hydrochloride is a topoisomerase II inhibitor with potent anti-tumor activity. Daunorubicin hydrochloride inhibits DNA and RNA synthesis. Daunorubicin hydrochloride is a cytotoxin that inhibits cancer cell viability and induces apoptosis and necrosis. Daunorubicin hydrochloride is also an anthracycline antibiotic. Daunorubicin hydrochloride can be used in the research of infection and variety of cancers, including leukemia, non-Hodgkin lymphomas, Ewing's sarcoma, Wilms' tumor.

PF-573228 is a potent and selective FAK inhibitor with IC₅₀ of 4 nM for purified recombinant catalytic fragment of FAK.

ODN 1826 is a class B CpG ODN (oligodeoxynucleotide) and TLR9 agonist. ODN 1826 induces NO and iNOS production and enhances Apoptosis. ODN 1826 enhances immune surveillance. ODN 1826 increases aortic atherosclerotic plaque size. ODN 1826 has antitumor activity against lung cancer, glioma and melanoma.

Devimistat is a mitochondrial metabolism inhibitor. Devimistat is a lipoic acid antagonist that abrogates mitochondrial energy metabolism to induce apoptosis in various cancer cells.

Volasertib (BI 6727) is an orally active, highly potent and ATP-competitive Polo-like kinase 1 (PLK1) inhibitor with an IC₅₀ of 0.87 nM. Volasertib inhibits PLK2 and PLK3 with IC₅₀s of 5 and 56 nM, respectively. Volasertib induces mitotic arrest and apoptosis. Volasertib, a dihydropteridinone derivative, shows marked antitumor activity in multiple cancer models.

Deferoxamine (Deferoxamine B) is an iron chelator (binds to Fe(III) and many other metal cations), is widely used to reduce iron accumulation and deposition in tissues. Deferoxamine upregulates HIF-1α levels with good antioxidant activity. Deferoxamine also shows anti-proliferative activity, can induce apoptosis and autophagy in cancer cells. Deferoxamine can be used in studies of diabetes, neurodegenerative diseases as well as anti-cancer and anti-COVID-19.

CC-885, a cereblon (CRBN) modulator, acts as a molecular glue degrader targeting GSPT1 with a K_d of 350 nM. CC-885 binds to CRBN to alter the substrate specificity of the CRL4 E3 ligase, promoting the ubiquitination and proteasomal degradation of GSPT1, BNIP3L, PLK1, CDK4, IKZF1/3, GSPT2, WIZ, CHD7, GOLM1, CK1α and ETS1. CC-885 induces apoptosis, cell cycle arrest, transcriptional downregulation and antiproliferation in cancer cells. CC-885 is applicable to research related to relapsed/refractory acute myeloid leukemia, MYC-driven tumors, metastatic castration-resistant prostate cancer, multiple myeloma, hepatocellular carcinoma, glioblastoma, VHL-deficient clear cell renal cell carcinoma and non-small cell lung cancer.

Importazole is a small molecule inhibitor of the nuclear transport receptor importin-β.

Cobimetinib (GDC-0973, RG7420) is a potent, selective and oral MEK1 inhibitor with an IC₅₀ of 4.2 nM for MEK1.

Prexasertib (LY2606368) is a selective, ATP-competitive second-generation checkpoint kinase 1 (CHK1) inhibitor with a K_i of 0.9 nM and an IC₅₀ of <1 nM. Prexasertib inhibits CHK2 (IC₅₀=8 nM) and RSK1 (IC₅₀=9 nM). Prexasertib causes double-stranded DNA breakage and replication catastrophe resulting in apoptosis. Prexasertib shows potent anti-tumor activity.

8-Bromo-cAMP (8-Br-Camp), a cyclic AMP analog, is an activator of cyclic AMP-dependent protein kinase (PKA). 8-Bromo-cAMP has anti-proliferative and apoptotic effects against cancer cells.

Thalidomide inhibits cereblon (CRBN), a part of the cullin-4 E3 ubiquitin ligase complex CUL4-RBX1-DDB1, with a K_d of ∼250 nM, and has immunomodulatory, anti-inflammatory and anti-angiogenic cancer properties. Thalidomide can work as molecular glue to potentiate substrate.

Ipatasertib (GDC-0068) is an orally active, highly selective and ATP-competitive pan-Akt inhibitor with IC₅₀ values of 5, 18, 8 nM for Akt1/2/3, respectively. Ipatasertib synchronously activates FoxO3a and NF-κB through inhibition of Akt leading to p53-independent activation of PUMA. Ipatasertib also induces apoptosis in cancer cells and inhibits tumor growth in xenograft mouse models.

Infigratinib (BGJ-398; NVP-BGJ398) is a potent inhibitor of the FGFR family with IC₅₀s of 0.9 nM, 1.4 nM, 1 nM, and 60 nM for FGFR1, FGFR2, FGFR3, and FGFR4, respectively.

Capmatinib (INC280; INCB28060) is a potent, orally active, selective, and ATP competitive c-Met kinase inhibitor (IC₅₀=0.13 nM). Capmatinib can inhibit phosphorylation of c-MET as well as c-MET pathway downstream effectors such as ERK1/2, AKT, FAK, GAB1, and STAT3/5. Capmatinib potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively induces apoptosis. Antitumor activity. Capmatinib is largely metabolized by CYP3A4 and aldehyde oxidase.

Cl-amidine hydrochloride is an orally active peptidylarginine deminase (PAD) inhibitor, with IC₅₀ values of 0.8 μM, 6.2 μM and 5.9 μM for PAD1, PAD3, and PAD4, respectively. Cl-amidine hydrochloride induces apoptosis in cancer cells. Cl-amidine hydrochloride induces microRNA (miR)-16 (miRNA-16, microRNA-16) expression and causes cell cycle arrest. Cl-Amidine hydrochloride prevents histone 3 citrullination and neutrophil extracellular trap formation, and improves survival in a murine sepsis model.

Salidroside (Rhodioloside) is a prolyl endopeptidase inhibitor. Salidroside alleviates cachexia symptoms in mouse models of cancer cachexia via activating mTOR signalling. Salidroside protects dopaminergic neurons by enhancing PINK1/Parkin-mediated mitophagy.

LW6 (HIF-1α inhibitor) is a novel HIF-1 inhibitor with an IC₅₀ value of 4.4 μM, and it is also an inhibitor of MDH2. LW6 decreases HIF-1α protein expression without affecting HIF-1β expression.