ANALYTICAL & LABORATORY EQUIPMENT
viral clearance, tumour elimination and attenuation of inflammation. In addition to designing synthetic molecules that recognise and interact in cellular processes, to benefit patients the drugs must be safe and readily accessible. Many modern treatments require a combination of small molecule drugs to achieve an optimal therapeutic benefit, but some drug combinations can have a sub-optimal effect or have side effects due to drug-drug interactions. Tis is because most small molecule drugs are subject to metabolism by enzymes in the liver, since the liver perceives the drugs as foreign substances to be eliminated from the body. Te liver uses a plethora of enzymes to convert drugs into water- soluble forms for elimination from the body. Unfortunately, when multiple drugs are used in combination or simultaneously, these enzymes cannot function efficiently. Tis leads to inadequate metabolism, or build-up of the individual drugs in higher levels in the blood, leading to potential toxicity. Such drug-drug interactions can also result in sub-therapeutic levels of the individual drugs. By contrast, SMNH compounds are chemically modified at key sites in the molecule to confer druggability attributes while retaining their ability to interact with target cellular components. Tus, SMNH compounds possess the pharmaceutical attributes of small molecule drugs and yet have better aqueous solubility, less metabolic liability and less likelihood of drug-drug interactions. Te compounds can therefore be combined with other drugs when needed.
Being small molecules, SMNH compounds are also relatively easily manufactured in larger scale by well- established processes and operations commonly employed in the pharmaceutical world. Many currently used small molecule drugs require numerous steps for large-scale manufacture. On the other hand, manufacture of these compounds involves fewer steps. Te ability to readily manufacture compounds at larger scale
enables substantial reduction in the cost of goods and can provide easier access to drugs for millions of patients suffering from a variety of diseases.
The mechanism of Spring Bank’s Inarigivir molecule
SMNH COMPOUND APPLICATION EXAMPLES Hepatitis B. Chronic HBV patients have a dysfunctional immune system that is unable to clear the virus from the body. Current drugs for HBV, such as nucleosides or nucleotides (Nucs) are designed primarily to suppress viral replication. Tese drugs do not eliminate the virus, have side effects and require life-long therapy – stoppage of treatment results in viral rebound. Tere is therefore a significant need for drugs that can affect “functional cure” of chronic HBV during a finite duration of therapy. Tis can be achieved by a combination of drugs in which immunomodulation will be the key component. One example of such a drug using SMNH chemistry is Inarigivir, a small molecule developed by Spring Bank for the treatment of chronic hepatitis B virus infection. Designed to be selectively activated within HBV-infected cells, Inarigivir binds the cellular protein, retinoic acid-inducible gene 1 (RIG-I), to both inhibit viral replication and cause the induction of intracellular interferon
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