Library Highlights

Meet some of our success cases

LASSBio-294

LASSBio-294 is an N-acylhydrazone (NAH) derivative with a remarkable positive inotropic effect and significant vasodilatory properties. This prototype was able to decrease the skeletal and cardiac muscle fatigue. This profile suggests the potential for treatment of patients suffering from conditions in which muscle fatigue is a debilitating symptom, for example, chronic heart failure. A lead compound with these features has many appeals because the therapy of choice currently still consist of Digitalis drugs Digoxin and Digitoxin, which are not the most adequate choices due to their narrow therapeutic index. Additionally, LASSBio-294 has a versatile chemical structure that allows for many molecular modifications, turning it into a suitable lead for further optimization steps.

J. Pharmacol. Exp. Ther. 2001, 299, 558-566.

WO 2000078754.

LASSBio-596

LASSBio-596 is a lead compound originally designed as a multi-target anti-inflammatory prototype. Its main action is through the inhibition of phosphodiesterase-4 (PDE4) and phosphodiesterase-5 (PDE5) enzymes and reduction of TNF-α production. LASSBio-596 has shown to be active in several in vivo assays, reducing inflammation and improving the lung functional properties in both acute and chronic pharmacological models. Also, it demonstrated a lack of genotoxicity in a concentration as high as 250 µg/mL. These features make LASSBio-596 a suitable lead for the development of novel candidates for the treatment of inflammatory-based diseases, such as asthma.

Bioorg. Med. Chem. 2002, 10, 3067-3073.

Eur. Respir. J. 2003, 22, 20-27.

LASSBio-1359

LASSBio-1359 is a N-methyl-N-acylhydrazone identified in a novel combinatory class of N-acylhydrazone (NAH) derivatives. It has shown to be a selective and potent phosphodiesterase-4 (PDE4) inhibitor associated with anti-TNF-α properties measured both in vitro and in vivo. Phosphodiesterases (PDEs) play a critical role in maintaining the cellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). The involvement of PDE4 in pathological processes suggests a great potential for pharmacological intervention in a variety of inflammatory, vascular, angiogenic, and neurological disorders. Thus, LASSBio-1359 represents a great starting point in a drug discovery campaign within this context.

J. Med. Chem. 2012, 55, 7525−7545.

LASSBio-1819

LASSBio-1819 is a novel 2-chloro-4-anilino-quinazoline dual inhibitor of the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 2 (VEGFR-2). Among EGFR inhibitors, either already approved by the FDA or currently in clinical trials, the 4-anilinoquinazoline class of compounds stands out. LASSBio-1819 differs from the first generation of EGFR inhibitors by the presence of a 2-chloro-quinazoline core containing a para-amide group at the aniline moiety instead of ordinary halogenated rings. This provides additional hydrogen bond points of interaction with the binding site of the therapeutic targets. The EGFR and VEGFR-2 are validated targets in the cancer therapy context and their combined inhibition might be synergistic for achieving both anti-tumor activity and resistance prevention. This profile shows that LASSBio-1819 is a versatile choice as a starting lead for the design of multi-kinase inhibitor with great room for structural customization.

Eur. J. Med. Chem. 2014, 71, 1-14.