Marketed Deuterated Drugs
1. Deucravacitinib
Drug | Deucravacitinib (BMS-986165) |
---|---|
Parent Drug | NA |
Therapeutic indication | Plaque psoriasis |
FDA approval | September 2022 |
Originator | Bristol Myers Squibb |
Development | Bristol Myers Squibb |
Orphan Drug Designation | No |
New Chemical entity | Yes |
Deucravacitinib represents a novel approach to targeting autoimmune and inflammatory diseases through selective inhibition of TYK2. Its mechanism of action involves allosteric inhibition of TYK2 and subsequent blockade of critical cytokine signaling pathways, allowing for effective modulation of the immune system with potentially fewer side effects compared to less selective JAK inhibitors. This specificity and efficacy make deucravacitinib a promising therapeutic option for patients with conditions driven by dysregulated cytokine activity.
2. Deutetrabenazine
Drug | Deutetrabenazine (Austedo) |
---|---|
Parent Drug | Tetrabenazine |
Therapeutic indication | Drug-induced dyskinesia |
FDA approval | April 2017 |
Originator | Auspex Pharmaceuticals |
Development | Teva Pharmaceutical |
Orphan Drug Designation | Yes |
ODD Exclusivity | 7 years |
NCE Exclusivity | 5 years |
Approval | Hybrid 505(B)(2) |
Deutetrabenazine is a deuterated form of tetrabenazine, designed to treat hyperkinetic movement disorders such as Huntington's disease and tardive dyskinesia. The deuteration process involves replacing specific hydrogen atoms with deuterium, which slows the metabolism of the drug and prolongs its effect. Deutetrabenazine and its active metabolites act as inhibitors of the vesicular monoamine transporter 2 (VMAT2). VMAT2 is responsible for transporting neurotransmitters such as dopamine, serotonin, norepinephrine, and histamine into synaptic vesicles in neurons. By inhibiting VMAT2, deutetrabenazine decreases the uptake of these neurotransmitters into synaptic vesicles, leading to a reduction in their storage and release into the synaptic cleft.
3. Donafenib
Drug | Donafenib |
---|---|
Parent Drug | Sorafenib |
Therapeutic indication | Renal Cell Carcinoma, Hepatocellular Carcinoma, Thyroid Cancer |
FDA approval | NA (Approved only in China in June 2021) |
Originator | Suzhou Zelgen Biopharmaceuticals |
Development | Suzhou Zelgen Biopharmaceuticals |
Orphan Drug Designation | No |
New Chemical entity | Yes |
Donafenib is deuterated sorafenib, multi kinase inhibitor, but has been modified to enhance its efficacy and safety profile. Donafenib inhibits several receptor tyrosine kinases (RTKs) involved in tumor growth and angiogenesis. These include vascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3), platelet-derived growth factor receptor beta (PDGFR-β), and RAF kinases. By blocking VEGFRs, donafenib disrupts the signaling pathways that promote angiogenesis, the process by which new blood vessels form from pre-existing ones. This is crucial for tumor growth and metastasis, as tumors require a blood supply to obtain nutrients and oxygen.