Modulateur d'interaction protéine-protéine

Inhibitor of BET bromodomain

Inhibits anti-apoptotic proteins Bcl-2, Bcl-xl and Bcl-w. Synergistic with chemotherapy and radiotherapy in several tumour cell lines. Potent activity as a single agent in lymphoid cancer and small cell lung cancer (SCLC) cell lines. Causes tumour regression in SCLC xenograft tumour in vivo.

Inhibitor of transcriptional coactivator PGC-1a; anti-diabetic agent

Inhibitor of the Forkhead box M1 (FOXM1), an oncogene and a transcription factor regulating cell cycle progression, DNA damage repair and cell renewal. RCM 1 weakens the FOXM1 activity by inhibiting its nuclear localisation and increasing its degradation in proteasomes. The compound showed potential for asthma treatment since it inhibited goblet cell metaplasia and IL-13 signalling in mice.

Activater of the Nrf2 pathway and an inhibitor of the NF-κB pathway.  Possible applications have extended to anti-viral treatment of COVID-19.

Anti-microtubular agent; antineoplastic

Inhibitor of protein tyrosine phosphatase PTP1B

Inhibitor of clathrin-mediated endocytosis (CME) and ligand to the clathrin heavy chain (CHC). ES9-17 is an inhibitor of the CHC function with EC50 of 13 μM in plant model Arabidopsis thaliana. ES9-17 is a non-protonophoric CME inhibitor and it does not alter the cytoplasmic pH levels substantially. In a mammalian cell line HeLa, ES9-17 reduced the uptake of transferrin, which is a CME-driven process.

A cytotoxic taxane and anti-microtubule agent with anti-proliferative activity. Docetaxel binds to the β-subunit of tubulin, which results in increased polymerisation and stabilisation of microtubules. The compound interferes with microtubule dynamics, which leads to the cell cycle arrest in the G2/M phase and apoptosis. The compound has significant inhibitory activity in solid tumors either alone or in combination with other chemotherapeutic agents.

Tubulin binding agent; targets tumour vasculature

Inhibits the mitochondrial outer mebrane protein mitoNEET, anti-leukaemic

Heat shock protein 90 (HSP90) inhibitor

Rivaroxaban is a natural drug that is a direct factor Xa inhibitor. It has been shown to be an effective therapy for the treatment of atrial fibrillation, deep vein thrombosis (DVT) and pulmonary embolism (PE). It works by inhibiting the enzyme, thrombin, which is responsible for the formation of blood clots. Rivaroxaban also has an effect on the coagulation system by decreasing the levels of fibrinogen and increases in antithrombin III. This drug does not have any specific antidote, but it can be reversed with heparin. Pharmacodynamics and drug interactions have been studied extensively in preclinical models, demonstrated by the concentration-time curves. Rivaroxaban is part of our Bio-X ™ Range. These products are aimed at life science researchers who need high quality ready to use products for assay development, screening or other R&D work. With a solubility datasheet and convenient vials, our Bio-X ™ products are in stock across our global warehouses for rapid delivery and ease of use.

A Bad-like BH3 mimetic with strong affinity for Bcl-xl, Bcl-2 and Bcl-w that promotes BIM-mediated apoptosis. Enhanced efficacy when combined with other chemotherapies in xenograft models of B-cell malignancies and SCLC. Has senolytic effects on senescent cells, demonstrating revival of aged HSCs in vivo.

Inhibitor of pan-sirtuins (IC50 = 15, 10, 33 µM for SIRT1, 2 and 3 respectively), by binding to the active catalytic site. Selectivity for sirtuins was demonstrated when tested for activity on a panel of kinases, nuclear receptors, ion channels, transporters and GPCRs.

Activator of p53; inhibitor of NF-?B

Induces Kruppel like factor 4 (KLF4) and reduces the expression of MYC.  Anti-tumor activity of APTO 253 has been demonstrated in AML and haematological malignancies. Inducing KLP4 expression in ovarian cancer cells using APT0 253 sensitises cells to cisplatin  and paclitaxel. BRCA1/2-deficient cancer cells are hypersensitive to APTO 253, which mediates its action by causing DNA damage.

Antagonist of proto-oncogene MDM2 and its interaction with p53

A small molecule inhibitor of polycomb complex protein BMI-1, a gene often overexpressed in tumors and therefore a popular therapeutic target in cancer. Anti-tumor effects of PTC 209 have been demonstrated in colorectal carcinoma, acute myeloid leukemia, multiple myeloma and head neck squamous cell carcinoma. As a regulator of self-renewal, inhibition of BMI-1 by PTC 209 also reduces growth of colorectal cancer initiating cells.

Potent and selective inhibitor of polycomb repressive complex 2 (PRC2), by binding to the K27me3-pocket of the regulatory EED subunit. Inhibits H3K27 methylation in histone 3. Has anti-tumor activity in murine xenograft models. Synergistic with EZH2 inhibitor against cancer cell growth.