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Targeting the immunotherapy potential of cytokines IL-12 and IL-18 with new advancements in protein engineering

Drug Target Review

At Alkermes , our interdisciplinary team of protein engineers, immunologists, pharmacologists, and analytical scientists is investigating the biology of several immunomodulatory cytokines including IL-12 and IL-18 to develop novel versions of these molecules with the goal of harnessing their therapeutic potential.

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The future of lymphoma treatment

Drug Target Review

We use hydrophilic linkers, which prevent ADC aggregation and generate highly stable ADCs, in combination with a unique attachment site on the antibody to create ADCs that retain pharmacokinetic properties similar to the original unconjugated antibody. Do Araris’ ADCs require antibody engineering?

Treatment 114
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Sensory-motor neuropathy in Mfn2 T105M knock-in mice and its reversal by a novel piperine-derived mitofusin activator [Neuropharmacology]

ASPET

Here, we describe motor and sensory neuron dysfunction characteristic of clinical CMT type 2A in a CRISPR/Casp-engineered Mfn2 Thr105Met (T105M) mutant knock-in mouse. We further demonstrate that daily oral treatment with a novel mitofusin activator derived from the natural product piperine can reverse these neurological phenotypes.

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Drug-induced long QT syndrome: Concept and non-clinical models for predicting the onset of drug-induced torsade de pointes in patients in compliance with ICH E14/S7B guidance [Minireview]

ASPET

This review details the onset mechanisms of drug-induced TdP, including I Kr inhibition, pharmacokinetic factors, autonomic regulation and reduced repolarization reserve. It also explores the utility of proarrhythmic surrogate markers (J-T peak , T peak -T end and terminal repolarization period) besides QT interval.

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Target cell activation of a structurally novel NLRP3 inhibitor NT-0796 enhances potency [Drug Discovery and Translational Medicine]

ASPET

Profiling NT-0796 in mice humanized with respect to CES-1 biology enables critical modeling of the pharmacokinetics and pharmacodynamics of this novel therapeutic candidate. To study pharmacodynamics of NT-0796 in vivo, a mouse line was engineered possessing more human-like traits with respect to carboxylesterase biology.

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Breakthrough drug candidates and cancer treatment innovations

Drug Target Review

ZW191 is an antibody-drug conjugate (ADC) that is engineered to target folate receptor-⍺ (FR⍺), a protein that has limited expression in normal tissues but is often elevated on a variety of tumours including epithelial ovarian, endometrial, triple negative breast and lung adenocarcinoma.

Treatment 100
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Developing the next generation of antibody drug conjugates

Drug Target Review

Despite excellent pharmacokinetic and stable antibody-linker connections, such ADCs have yet to receive market approval. How do the selection of linkers and conjugation sites impact the pharmacokinetics and therapeutic window of an ADC? This approach offers the advantage of using chemical modification.