Small molecules
ENGLISH DEUTSCH
WILEX AG also has small molecules or low molecular weight compounds in its portfolio of therapeutic product candidates. Small molecules are characterised by having a molecular weight not exceeding 800 g/mol (800 Dalton). Unlike large molecules (e.g. antibodies), the low molecular weight of small molecules enables them to diffuse across cell membranes and effectively target intracellular sites. At such sites, they can block signals that play a role in tumour growth or inflammatory diseases, for example.
Tumour cells use specific signal transduction pathways to divide more quickly and therefore proliferate more rapidly than normal cells. By producing proteases (enzymes that break down proteins), tumour cells can invade surrounding tissue and the lymphatic/cardiovascular system, and then metastasise. As a rule, these systems function by particular transmitter molecules binding to proteins on the cell surface known as “receptors”. An approach that utilises specific small-molecule inhibitors to target the binding sites and obstruct these systems may have the potential to control tumour growth and block metastasis.
The product candidate MESUPRON® is one such oral small-molecule protease inhibitor and is designed to block the urokinase plasminogen activator system (uPA system). This system plays a key role in the growth, spread and metastasis of various malignant tumours. The uPA programme provided the scientific basis for the establishment of WILEX in 1997. The uPA content in the tumour enables doctors to predict the statistical likelihood of a patient’s survival: Patients whose tumours have a high level of uPA have a statistically shorter survival period compared to patients whose tumours have a low uPA level. MESUPRON® is being tested as the first small-molecule uPA inhibitor in a clinical Phase II programme.
WILEX is also working on two further small-molecule inhibitors: a MEK inhibitor and a PI3K inhibitor, which were brought into the development programme in 2009 as part of the strategic alliance with UCB Pharma S.A.
The MEK inhibitor (WX-554) is currently undergoing testing in a Phase I programme and is a highly promising candidate for tumour therapy. The MEK protein is part of the MAPK (mitogen activated protein kinase) pathway. This pathway uses a cascade of other proteins to transmit signals from receptors on the cell surface to the cell nucleus, where it stimulates cell differentiation and cell division. Other pathway components include the kinases Ras, Raf and ERK1/2. The MEK signalling pathway is over expressed in more than 30% of cancers, resulting in increased tumour growth and proliferation.
The PI3K inhibitor WX-037 is currently undergoing preclinical development. The phosphatidylinositol-3-kinase (PI3K) pathway sends a “growth” signal to the nucleus of a cancer cell. Increased activity in the PI3K pathway is commonly found in tumour cells and plays a role in tumour development. It has been shown that mutations of the PI3K pathway are present in many types of cancer. Developing an inhibitor for the highly regulated PI3K pathway is thus of therapeutic interest.
