Tailor-made amino acid-derived pharmaceuticals approved by the FDA in 2019

Yin, Zizhen; Hu, Wencheng; Zhang, Wei; Konno, Hiroyuki; Moriwaki, Hiroki; Izawa, Kunisuke; Han, Jianlin; Soloshonok, Vadim A.

doi:10.1007/s00726-020-02887-4

Cited by 33 publications

(23 citation statements)

References 158 publications

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“…When R 1 = –CO 2 R or –CH 2 CO 2 R, the structures include α- [ 36 , 105 , 106 ] and β-amino [ 31 , 32 ] acid derivatives, respectively, such as peptides and peptidomimetics. There is no need to emphasize the exceptional hydrogen bonding properties of the N-acyl amine group in 4 and the obvious importance of this class of compounds in modern organic synthesis, medicinal chemistry, and drug design [ 107 , 108 , 109 , 110 , 111 ]. Finally, the 1,1′-bi-2-phenol structural unit present in 5 exhibits extraordinary hydrogen bonding properties and is responsible for the very high SDE magnitude often observed for these compounds [ 12 , 13 , 15 , 76 , 77 , 112 , 113 , 114 , 115 , 116 ].…”

Section: Preview Of the Sdementioning

confidence: 99%

Recommended Tests for the Self-Disproportionation of Enantiomers (SDE) to Ensure Accurate Reporting of the Stereochemical Outcome of Enantioselective Reactions

et al. 2021

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The purpose of this review is to highlight the necessity of conducting tests to gauge the magnitude of the self-disproportionation of enantiomers (SDE) phenomenon to ensure the veracity of reported enantiomeric excess (ee) values for scalemic samples obtained from enantioselective reactions, natural products isolation, etc. The SDE always occurs to some degree whenever any scalemic sample is subjected to physicochemical processes concomitant with the fractionation of the sample, thus leading to erroneous reporting of the true ee of the sample if due care is not taken to either preclude the effects of the SDE by measurement of the ee prior to the application of physicochemical processes, suppressing the SDE, or evaluating all obtained fractions of the sample. Or even avoiding fractionation altogether if possible. There is a clear necessity to conduct tests to assess the magnitude of the SDE for the processes applied to samples and the updated and improved recommendations described herein cover chromatography and processes involving gas-phase transformations such as evaporation or sublimation.

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Section: Preview Of the Sdementioning

confidence: 99%

Recommended Tests for the Self-Disproportionation of Enantiomers (SDE) to Ensure Accurate Reporting of the Stereochemical Outcome of Enantioselective Reactions

et al. 2021

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“…[23][24][25] There are 24 small-molecule drugs have been approved by FDA in 2019, among all these drugs, 13 contain a residue of amino acids, di-amines or amino-alcohols, which are commonly considered to be derived from the parent amino acids. 26 Therefore, modification of the structure of pinocembrin by introducing a fragment containing an amino acid residue probably lead to a generation of compounds with useful biological properties.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Pinocembrin Amino Acid Derivatives and Their Antiaging Effect on Caenorhabditis elegans via the Modulating DAF-16/FOXO

Wang¹,

Feng²,

Du³

et al. 2021

DDDT

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Pinocembrin is a dihydroflavonoid, which is widely found in several plant species. Although pinocembrin has good pharmacological activity, it has poor water solubility and low bioavailability. Therefore, we have modified the structure of pinocembrin with a combination of different amino acids to solve this problem. Moreover, the effect of the antiaging activity of them has not been explored. We aim to investigate the effect of pinocembrin and its amino acid derivatives on the aging of Caenorhabditis elegans. Methods: Pinocembrin was spliced with different amino acids in order to obtain their corresponding derivatives. The preliminary research of pinocembrin and its amino acid derivatives on antiaging effect was studied by using the C. elegans model. Among all the compounds, the one shows the best antiaging effect was then studied on antiaging mechanism. The protective effect on nematodes under emergency conditions was explained by detecting the ROS content and sod-3p::GFP fusion protein expression in nematodes; the possible anti-aging mechanism of nematodes was determined by DAF-16 nuclear localization experiment and the survival curve of transgenic nematodes model under stress conditions. Results: Pb-3 showed the best effect on increasing tolerance to thermal and oxidative stress and reduce the accumulation of lipofuscin. In the assay of C. elegans, pb-3 reduced intracellular ROS accumulation. Application of pb-3 to the transgenic mutant TJ356 induced the translocation of the transcription factor DAF-16 from the cytosol to the nucleus, and modulated the expression of SOD-3 (downstream genes of daf-16), which regulates longevity in C. elegans. Moreover, pb-3 did not prolong the lifespan of daf-16, age-1, daf-2 and hsp16.2 mutants, suggesting that these genetic pathways are involved in mediating the antiaging effects of pb-3. Conclusion:The antioxidant and antiaging properties of pb-3 may involve in the DAF-16/ FOXO transcription process. Pinocembrin amino acid derivatives might be a novel agent for antiaging therapy.

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“…As of 2020, over 70 peptide drugs have been approved by FDA, and over 160 peptides are currently in clinical testing in various disease settings (Lau & Dunn, 2018; Zhang et al, 2020). There were 13 new tailor‐made amino acids‐derived pharmaceuticals gained FDA approval in 2019 (Yin et al, 2020). Importantly, two PDCs including 111 Indium‐pentreotide (Octreoscan®) for diagnostic neuroendocrine tumor imaging and 177 Lu‐DOTA‐[Tyr 3 ]‐octreotate (Lutathera®) for neuroendocrine tumor treatment have been approved by the FDA (Hoppenz et al, 2020).…”

Section: Current Status and Challenges For Moving Pdc To Clinicmentioning

confidence: 99%

Brain penetrating peptides and peptide–drug conjugates to overcome the blood–brain barrier and target CNS diseases

Zhou

Smith

Liu

2021

WIREs Nanomed Nanobiotechnol

120

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Nearly one in six people worldwide suffer from disorders of the central nervous system (CNS). There is an urgent need for effective strategies to improve the success rates in CNS drug discovery and development. The lack of effective technologies for delivering drugs and genes to the brain due to the blood–brain barrier (BBB), a structural barrier that effectively blocks most neurotherapeutic agents from reaching the brain, has posed a formidable hurdle for CNS drug development. Brain‐homing and brain‐penetrating molecular transport vectors, such as brain permeable peptides or BBB shuttle peptides, have shown promise in overcoming the BBB and ferrying the drug molecules to the brain. The BBB shuttle peptides are discovered by phage display technology or derived from natural neurotropic proteins or certain viruses and harness the receptor‐mediated transcytosis molecular machinery for crossing the BBB. Brain permeable peptide–drug conjugates (PDCs), composed of BBB shuttle peptides, linkers, and drug molecules, have emerged as a promising CNS drug delivery system by taking advantage of the endogenous transcytosis mechanism and tricking the brain into allowing these bioactive molecules to pass the BBB. Here, we examine the latest development of brain‐penetrating peptide shuttles and brain‐permeable PDCs as molecular vectors to deliver small molecule drug payloads across the BBB to reach brain parenchyma. Emerging knowledge of the contribution of the peptides and their specific receptors expressed on the brain endothelial cells, choice of drug payloads, the design of PDCs, brain entry mechanisms, and delivery efficiency to the brain are highlighted. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease

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Tailor-made amino acid-derived pharmaceuticals approved by the FDA in 2019

Cited by 33 publications

References 158 publications

Recommended Tests for the Self-Disproportionation of Enantiomers (SDE) to Ensure Accurate Reporting of the Stereochemical Outcome of Enantioselective Reactions

Recommended Tests for the Self-Disproportionation of Enantiomers (SDE) to Ensure Accurate Reporting of the Stereochemical Outcome of Enantioselective Reactions

Synthesis of Novel Pinocembrin Amino Acid Derivatives and Their Antiaging Effect on Caenorhabditis elegans via the Modulating DAF-16/FOXO

Brain penetrating peptides and peptide–drug conjugates to overcome the blood–brain barrier and target CNS diseases

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