Apoptosis Inducer

IR-780 is a near-infrared fluorescent probe for in vivo imaging of tumor cells. IR-780 is transported into tumor cells via OATPs and ABCB10, with uptake dependent on glycolytic activity and plasma membrane potential. IR-780 preferentially accumulates in tumor cell mitochondria, including those of drug-resistant cancer cells, without chemical conjugation. IR-780 generates reactive oxygen species (ROS), induces hyperthermia and apoptosis, inhibits tumor growth and recurrence, and modulates HSP70 expression upon ultrasound or 808 nm laser exposure. IR-780 acts as a sonosensitizer, photodynamic and photothermal agent, and drug delivery carrier, with low acute imaging-dose toxicity and rapid vital organ clearance. IR-780 can be used for the research of cancer, such as breast cancer, lung cancer, and non-small cell lung cancer (NSCLC).

β-Elemene ((-)-β-Elemene; Levo-β-elemene) is isolated from natural plant Curcuma aromatica with an antitumor activity. β-Elemene can induce cell apoptosis.

Degrasyn (WP1130) is a cell-permeable deubiquitinase (DUB) inhibitor, directly inhibiting DUB activity of USP9x, USP5, USP14, and UCH37. Degrasyn has been shown to downregulate the antiapoptotic proteins Bcr-Abl and JAK2.

PCI-34051 is a potent and selective HDAC8 inhibitor with IC₅₀ of 10 nM, with >200-fold selectivity over the other HDAC isoforms.

Vincristine (Leurocristine; NSC-67574; 22-Oxovincaleukoblastine) is a microtubule inhibitor that disrupts microtubule polymerization by binding to β-tubulin (with a K_i of 85 nM in bovine), arrests the cell cycle and induces apoptosis. Vincristine inhibits cell replication, tumor blood flow and the proliferation of various cancer cells, while triggering effects such as oxidative stress, inflammation, calcium overload, epithelial-mesenchymal transition and peripheral neuropathic pain. Vincristine upregulates the expression of various transporters and nuclear receptors, and enriches gastric cancer stem-like cells. Vincristine is used in research related to various tumors including acute lymphoblastic leukemia, lymphoma, melanoma, gastric cancer, solid tumors and sarcomas.

Aloe emodin (Rhabarberone) is a natural hydroxyanthraquinone with antitumor activities. aloe-emodin can bind with mTORC2 and inhibit its kinase activity. Aloe emodin exerts antiproliferation effects and induces cellular apoptosis. Aloe emodin also exhibits antiviral activity that against influenza A virus.

Guanosine triphosphate (GTP) trisodium is a critical nucleotide and regulator of cellular metabolism. Guanosine triphosphate trisodium promotes ribosomal DNA localization, pre-rRNA transcription and ribosome biogenesis by binding to RNA polymerase I and GPN proteins (GPN1/3). Guanosine triphosphate trisodium links MYC-dependent ribosome biogenesis to nucleotide sufficiency, acts as a metabolic gatekeeper supporting protein synthesis, DNA/RNA synthesis and cellular signal transduction, while also participating in the physiological activities of pancreatic β-cells and serving as an oxidative substrate for reactive oxygen species. In small cell lung cancer with high MYC expression, Guanosine triphosphate trisodium accumulates through the IMPDH-driven synthetic pathway, thereby affecting apoptosis and mitotic processes. Guanosine triphosphate trisodium is used in the research of small cell lung cancer, hepatoblastoma and cellular metabolism.

Salinomycin (Procoxacin), a polyether potassium ionophore antibiotic, selectively inhibits the growth of gram-positive bacteria. Salinomycin is a potent inhibitor of Wnt/β-catenin signaling, blocks Wnt-induced LRP6 phosphorylation. Salinomycin shows selective activity against human cancer stem cells.

RRx-001, a hypoxia-selective epigenetic agent and studied as a radio- and chem-sensitizer, triggers apoptosis and overcomes agent resistance in myeloma. RRx-001 exhibits potent anti-tumor activity with minimal toxicity. RRx-001 is a dual small molecule checkpoint inhibitor by downregulating CD47 and SIRP-α. RRx-001 is a potent inhibitor of G6PD and shows potent antimalarial activity.

Sorafenib (Bay 43-9006) tosylate 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 tosylate induces cell cycle arrest, autophagy, apoptosis, and PARP cleavage, reduces Bcl-2, Bcl-XL, cyclin D1 levels, and activates Bak and Bax. Sorafenib tosylate inhibits tumor growth and metastasis in mouse and rat models. Sorafenib tosylate can be used for cancer research, such as colon, breast, non-small-cell lung cancer (NSCLC), ovarian, pancreatic, melanoma, colorectal and hepatocellular carcinoma.

Torkinib (PP 242) is a selective and ATP-competitive mTOR inhibitor with an IC₅₀ of 8 nM. PP242 inhibits both mTORC1 and mTORC2 with IC₅₀s of 30 nM and 58 nM, respectively.

Xevinapant (AT-406) is a potent and orally bioavailable Smac mimetic and an antagonist of IAPs, and it binds to XIAP, cIAP1, and cIAP2 proteins with K_i of 66.4, 1.9, and 5.1 nM, respectively.

Crocin (Crocin I) is an orally active natural product that can be isolated from the stigma of Crocus sativus. Crocin inhibits tumor cell proliferation and promotes apoptosis through JAK pathway. Crocin has anti-inflammatory, antioxidant and antitumor activities .

Quinidine (15% dihydroquinidine) is an orally active antiarrhythmic agent. Quinidine (15% dihydroquinidine) reduces the expression level of P-gp, inhibits P-gp-mediated efflux, increases the intracellular accumulation of P-gp substrates, induces PARP cleavage and Caspase-3 activation, and elevates the proportion of Apoptotic cells at the sub-G1 phase. Quinidine (15% dihydroquinidine) exerts sustained block and open-channel block effects on I_K(f). Quinidine (15% dihydroquinidine) alters the urinary metabolic ratio of Amphetamine, modulates the Pentylenetetrazol-induced seizure threshold, and regulates the anticonvulsant effect of Dextromethorphan. Quinidine (15% dihydroquinidine) can be used in studies related to uterine sarcoma and seizures.

Selonsertib (GS-4997), an orally bioavailable, selective apoptosis signal-regulating kinase 1 (ASK1) inhibitor with a pIC₅₀ of 8.3, has been evaluated as an experimental treatment for diabetic nephropathy and kidney fibrosis.

Adapalene (CD271), a third-generation synthetic retinoid, is widely used for the research of acne. Adapalene is a potent RAR agonist, with AC₅₀s of 2.3 nM, 9.3 nM, and 22 nM for RARβ, RARγ, RARα, respectively. Adapalene also inhibits the enzymatic activity of GOT1 in a non-competitive manner. Adapalene exhibits anti-tumor activity.

Dinoprost (Prostaglandin F2α) is an orally active, potent prostaglandin F (PGF) receptor (FP receptor) agonist. Dinoprost is a luteolytic hormone produced locally in the endometrial luminal epithelium and corpus luteum (CL). Dinoprost plays a key role in the onset and progression of labour.

Sincalide (Cholecystokinin octapeptide, CCK-8) is a rapid-acting amino acid polypeptide hormone analogue of cholecystokinin (CCK) for intravenous use in postevacuation cholecystography. Sincalide is a major bioactive segment of CCK that retains most of the biological activities of CCK. Sincalide can promote gallbladder contraction by injection and helps diagnose gallbladder and pancreas disorders. Sincalide can increase bile secretion, cause the gallbladder to contract and relax the sphincter of Oddi, resulting in bile drainage into the duodenum. Sincalide is a major bioactive segment of CCK that retains most of the biological activities of CCK.

Pralatrexate is an antifolate and is a potent dihydrofolate reductasean (DHFR) inhibitor with a K_i of 13.4 pM. Pralatrexate is a substrate for folylpolyglutamate synthetase with improved cellular uptake and retention. Pralatrexate has antitumor activities and has the potential for relapsed/refractory T-cell lymphoma treatment. Pralatrexate is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

IU1 is a selective, reversible USP14 inhibitor with an IC₅₀ of 4-5 μM. IU1 binds USP14’s catalytic cleft to block deubiquitinase activity. IU1 induces calpain-dependent Tau cleavage, causes ATP deficits, reduces E1~Ub thioester levels and 26S proteasome assembly. IU1 enhances 26S proteasome chymotrypsin-like activity, modulates LC3B-dependent autophagy flux, reduces cancer cell proliferation and migration, and blocks G0/G1 to S phase cell cycle transition in follicular thyroid cancer cells. IU1 activates autophagy-lysosomal and ubiquitin-proteasome pathways, triggers apoptosis, and reduces cervical cancer cell growth. IU1 enhances degradation of proteasome substrates linked to neurodegenerative disease, accelerates oxidized protein degradation, and increases oxidative stress resistance. IU1 can be used for the research of Alzheimer’s disease, follicular thyroid cancer, ischemic stroke, cervical cancer, and neurodegenerative disease.