Medicinal Chemistry Projects
MDM2-p53 Inhibitors

In concert with Amgen scientists, Kalexsyn optimized a series of small molecule inhibitors of the MDM2-p53 protein-protein interaction. The original screening hit was chemically unstable and insoluble.  The new lead series developed by Kalexsyn was more tractable and showed good activity in cells where they were shown to cause p53-dependent inhibition of proliferation and apoptosis.
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MALT-1 Inhibitors
Kalexsyn led a medchem effort to develop inhibitors of the paracaspase MALT1 for the Helmholtz Institute in Munich.  In one series, the phenothiazines, synthetic methods were developed to thoroughly explore the binding interactions between this core template and the enzyme which led to the development of asymmetric routes to the compounds of high interest.  Several compounds are in late pre-clinical development for the treatment of MALT1-driven cancer or autoimmune diseases.
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Stable Label Projects
Labelled Glutathione
The synthesis of [1,2- 13C-2 , 15N-glycine]glutathione was successfully executed by the Kalexsyn Medicinal Chemistry Department. The synthetic route was significantly improved over the published route to obtain the multiple labeled isotope.
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Labelled Unoprostone
Unoprostone is used as an ophthalmic solution for the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Kalexsyn has prepared labelled material in support of metabolic and other development efforts
Custom Synthesis Projects
Aureobasidin A
Kalexsyn has prepared uniquely modified analogs of Aureobasidin A which have been found to have good activity against resistant organisms.
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A2E is a complex pyridinium salt that collects in the epithelial cells of the eye and has been implicated in the development of the disease macular degeneration. To study the role of A2E in the eye, a sizable quantity must be available. Our customers have entrusted Kalexsyn to provide quantities >1g of this complex retinal derivative.
Process Improvement Projects
Kalexsyn was instrumental in providing a scalable, patentable approach to the PPAR modulator, mitoglitazone. We developed an approach that started from commodity materials and via a previously unknown intermediate, thereby generating the IP the customer needed. Currently, our approach has been used in a pilot plant to generate several kilograms for advance clinical testing.
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Kalexsyn was charged with providing a scaleable route towards the complex pyridium salt, HI-6. Through significant experimentation, we were able to ascertain the key parameters in generating this salt with the ability to minimize homo-dimer impurities. Our efforts allowed us to rapidly provide >1kg of high quality HI-6 salt to our customer for further testing.