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  1. Article ; Online: Evaluation of a hapten conjugate vaccine against the "zombie drug" xylazine.

    Lin, Mingliang / Eubanks, Lisa M / Zhou, Bin / Janda, Kim D

    Chemical communications (Cambridge, England)

    2024  Volume 60, Issue 35, Page(s) 4711–4714

    Abstract: Xylazine has emerged as a primary adulterant in fentanyl, exacerbating the complexity of the opioid crisis. Yet, there is no approved drug that can reverse xylazine's pathophysiology. As a prelude to monoclonal antibodies being assessed as a viable ... ...

    Abstract Xylazine has emerged as a primary adulterant in fentanyl, exacerbating the complexity of the opioid crisis. Yet, there is no approved drug that can reverse xylazine's pathophysiology. As a prelude to monoclonal antibodies being assessed as a viable therapeutic, a vaccine inquiry was conducted evaluating the immune response in reversing xylazine induced behavior effects.
    MeSH term(s) Xylazine/chemistry ; Xylazine/pharmacology ; Haptens/chemistry ; Haptens/immunology ; Animals ; Vaccines, Conjugate/chemistry ; Vaccines, Conjugate/immunology ; Mice
    Chemical Substances Xylazine (2KFG9TP5V8) ; Haptens ; Vaccines, Conjugate
    Language English
    Publishing date 2024-04-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 1472881-3
    ISSN 1364-548X ; 1359-7345 ; 0009-241X
    ISSN (online) 1364-548X
    ISSN 1359-7345 ; 0009-241X
    DOI 10.1039/d4cc00883a
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Development of effective therapeutics for polysubstance use disorders.

    Lee, Jinny Claire / Janda, Kim D

    Current opinion in chemical biology

    2021  Volume 66, Page(s) 102105

    Abstract: Traditional pharmacotherapies for substance use disorders have focused on mono-substance abuse. However, recent epidemiological studies have found polysubstance use disorders (PUD) are becoming more prevalent and the abuse of adulterated drugs has led to ...

    Abstract Traditional pharmacotherapies for substance use disorders have focused on mono-substance abuse. However, recent epidemiological studies have found polysubstance use disorders (PUD) are becoming more prevalent and the abuse of adulterated drugs has led to increasing unintentional overdose deaths. Unfortunately, there are no approved pharmacological agents for PUD. Hence, a therapeutic model of interest to address this growing epidemic is immunopharmacotherapy, where individuals are inoculated with conjugate vaccines formulated with haptens that mimic the drug of abuse. These conjugate vaccines have demonstrated significant therapeutic potential against mono-substance abuse, thus recent studies have applied this model to address PUD. This review presents immunopharmacotherapeutic advancements against polysubstance abuse and discusses necessary developments for conjugate vaccines in order to effectively treat this unaddressed epidemic.
    MeSH term(s) Analgesics, Opioid ; Drug Overdose ; Humans
    Chemical Substances Analgesics, Opioid
    Language English
    Publishing date 2021-12-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1439176-4
    ISSN 1879-0402 ; 1367-5931
    ISSN (online) 1879-0402
    ISSN 1367-5931
    DOI 10.1016/j.cbpa.2021.102105
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4986: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Standing out from the crowd in treating COVID-19.

    Janda, Kim D / Iadarola, Michael J

    Medicine in drug discovery

    2020  Volume 6, Page(s) 100034

    Keywords covid19
    Language English
    Publishing date 2020-04-03
    Publishing country Netherlands
    Document type Editorial ; Comment
    ISSN 2590-0986
    ISSN (online) 2590-0986
    DOI 10.1016/j.medidd.2020.100034
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  4. Article ; Online: Demystifying the Druggability of the MYC Family of Oncogenes.

    Karadkhelkar, Nishant M / Lin, Mingliang / Eubanks, Lisa M / Janda, Kim D

    Journal of the American Chemical Society

    2023  Volume 145, Issue 6, Page(s) 3259–3269

    Abstract: The MYC family of oncogenes (MYC, MYCN, and MYCL) encodes a basic helix-loop-helix leucine zipper (bHLHLZ) transcriptional regulator that is responsible for moving the cell through the restriction point. Through the HLHZIP domain, MYC heterodimerizes ... ...

    Abstract The MYC family of oncogenes (MYC, MYCN, and MYCL) encodes a basic helix-loop-helix leucine zipper (bHLHLZ) transcriptional regulator that is responsible for moving the cell through the restriction point. Through the HLHZIP domain, MYC heterodimerizes with the bHLHLZ protein MAX, which enables this MYC-MAX complex to bind to E-box regulatory DNA elements thereby controlling transcription of a large group of genes and their proteins. Translationally, MYC is one of the foremost oncogenic targets, and deregulation of expression of the MYC family gene/proteins occurs in over half of all human tumors and is recognized as a hallmark of cancer initiation and maintenance. Additionally, unexpected roles for this oncoprotein have been found in cancers that nominally have a non-MYC etiology. Although MYC is rarely mutated, its gain of function in cancer results from overexpression or from amplification. Moreover, MYC is a pleiotropic transcription factor possessing broad pathogenic prominence making it a coveted cancer target. A widely held notion within the biomedical research community is that the reliable modulation of MYC represents a tremendous therapeutic opportunity given its role in directly potentiating oncogenesis. However, the MYC-MAX heterodimer interaction contains a large surface area with a lack of well-defined binding sites creating the perception that targeting of MYC-MAX is forbidding. Here, we discuss the biochemistry behind MYC and MYC-MAX as it relates to cancer progression associated with these transcription factors. We also discuss the notion that MYC should no longer be regarded as undruggable, providing examples that a therapeutic window is achievable despite global MYC inhibition.
    MeSH term(s) Humans ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics ; Proto-Oncogene Proteins c-myc/chemistry ; Transcription Factors/metabolism ; Oncogenes ; Neoplasms/drug therapy ; Neoplasms/genetics
    Chemical Substances Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Proto-Oncogene Proteins c-myc ; Transcription Factors
    Language English
    Publishing date 2023-02-03
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3155-0
    ISSN 1520-5126 ; 0002-7863
    ISSN (online) 1520-5126
    ISSN 0002-7863
    DOI 10.1021/jacs.2c12732
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Bonn / Germany

    Z 4' 55/32: Show issues
    Z 7.3: Show issues

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  5. Article ; Online: Discovery of PLD4 modulators by high-throughput screening and kinetic analysis.

    Lee, Jinny Claire / Shirey, Ryan J / Turner, Lewis D / Park, Hyeri / Lairson, Luke L / Janda, Kim D

    Results in chemistry

    2024  Volume 7

    Abstract: Phospholipase D3 (PLD3) and D4 (PLD4) are endolysosomal exonucleases of ssDNA and ssRNA that regulate innate immunity. Polymorphisms of these enzymes are correlated with numerous human diseases, including Alzheimer's, rheumatoid arthritis, and systemic ... ...

    Abstract Phospholipase D3 (PLD3) and D4 (PLD4) are endolysosomal exonucleases of ssDNA and ssRNA that regulate innate immunity. Polymorphisms of these enzymes are correlated with numerous human diseases, including Alzheimer's, rheumatoid arthritis, and systemic sclerosis. Pharmacological modulation of these immunoregulatory proteins may yield novel immunotherapies and adjuvants. A previous study reported a high-throughput screen (
    Language English
    Publishing date 2024-02-08
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2211-7156
    ISSN (online) 2211-7156
    DOI 10.1016/j.rechem.2024.101349
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  6. Article ; Online: Immunopharmacotherapeutic advancements in addressing methamphetamine abuse.

    Lee, Jinny Claire / Janda, Kim D

    RSC chemical biology

    2020  Volume 2, Issue 1, Page(s) 77–93

    Abstract: Methamphetamine (METH) is an illicit psychostimulant that is known to account for substance abuse disorders globally, second only to opioids, yet has no approved pharmacotherapies. Traditional therapies employ small molecule agonists or antagonists for ... ...

    Abstract Methamphetamine (METH) is an illicit psychostimulant that is known to account for substance abuse disorders globally, second only to opioids, yet has no approved pharmacotherapies. Traditional therapies employ small molecule agonists or antagonists for substance use disorders or overdose reversal by targeting drug-specific receptors in the brain. However, the comprehensive mechanism of METH on multiple sites within the central nervous system (CNS) implies its receptors lack the high affinity and specificity required for an "ideal" drug target. The alternative to pharmacotherapies is to sequester abused drugs in the periphery, effectively eliminating the effects from CNS receptor occupation through pharmacokinetic antagonism. This review presents updates on immunopharmacotherapeutic advancements in addressing methamphetamine abuse by focusing on the cultivation of research optimization strategies regarding hapten chemistry, carrier proteins, and adjuvants implemented in active immunization. Furthermore, we discuss necessary developments for each component of active immunopharmacotherapies and the future of active vaccines in treating METH use disorder.
    Language English
    Publishing date 2020-10-08
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2633-0679
    ISSN (online) 2633-0679
    DOI 10.1039/d0cb00165a
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  7. Article: Development of a vaccine against the synthetic opioid U-47700.

    Park, Hyeri / Lin, Mingliang / Zhou, Jian / Eubanks, Lisa M / Zhou, Bin / Janda, Kim D

    Frontiers in pharmacology

    2023  Volume 14, Page(s) 1219985

    Abstract: Opioid use disorders and overdose have become a major public health concern in recent years. U-47700, a New psychoactive substances (NPS) opioid, also known as "pinky" or "pink" has been identified as a new threat in the drug supply because of its ... ...

    Abstract Opioid use disorders and overdose have become a major public health concern in recent years. U-47700, a New psychoactive substances (NPS) opioid, also known as "pinky" or "pink" has been identified as a new threat in the drug supply because of its potency and abuse potential. Conjugate vaccines that can produce antibodies against target drug molecules have emerged as a promising tool to treat substance use disorders. Herein, we report the design, synthesis, and
    Language English
    Publishing date 2023-07-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2023.1219985
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Identification of Slow-Binding Inhibitors of the BoNT/A Protease.

    Patel, Ealin N / Turner, Lewis D / Hixon, Mark S / Janda, Kim D

    ACS medicinal chemistry letters

    2022  Volume 13, Issue 4, Page(s) 742–747

    Abstract: Botulinum neurotoxin A (BoNT/A) is a lethal toxin, which causes botulism, and is categorized as a bioterrorism threat, which causes flaccid paralysis and death. Botulinum A neurotoxicity is governed through its light chain (LC), a zinc metalloprotease. ... ...

    Abstract Botulinum neurotoxin A (BoNT/A) is a lethal toxin, which causes botulism, and is categorized as a bioterrorism threat, which causes flaccid paralysis and death. Botulinum A neurotoxicity is governed through its light chain (LC), a zinc metalloprotease. Pharmacological investigations aimed at negating BoNT/A's LC have typically looked to inhibitors that have been shown to inhibit the light chain's activity by reversible zinc chelation within its active site. This report outlines the first examples of nonpeptidic inhibitors of the BoNT/A LC that possess slow-binding kinetics, a needed logic to counteract the longevity of BoNT/A. Cyclopropane, alkyl, and alkenyl derivatives of 2,4-dichlorocinamic hydroxamic acid (DCHA) were shown to possess both one-step and two-step slow-binding kinetics. Structure-kinetic relationships (SKRs) were observed and were rationalized with the aid of docking models that predicted improved interactions with residues within a hydrophobic cleft adjacent to the active site.
    Language English
    Publishing date 2022-03-08
    Publishing country United States
    Document type Journal Article
    ISSN 1948-5875
    ISSN 1948-5875
    DOI 10.1021/acsmedchemlett.2c00028
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Catalytic Antibody Blunts Carfentanil-Induced Respiratory Depression.

    Lin, Mingliang / Eubanks, Lisa M / Karadkhelkar, Nishant M / Blake, Steven / Janda, Kim D

    ACS pharmacology & translational science

    2023  Volume 6, Issue 5, Page(s) 802–811

    Abstract: Carfentanil, the most potent of the fentanyl analogues, is at the forefront of synthetic opioid-related deaths, second to fentanyl. Moreover, the administration of the opioid receptor antagonist naloxone has proven inadequate for an increasing number of ... ...

    Abstract Carfentanil, the most potent of the fentanyl analogues, is at the forefront of synthetic opioid-related deaths, second to fentanyl. Moreover, the administration of the opioid receptor antagonist naloxone has proven inadequate for an increasing number of opioid-related conditions, often requiring higher/additional doses to be effective, as such interest in alternative strategies to combat more potent synthetic opioids has intensified. Increasing drug metabolism would be one strategy to detoxify carfentanil; however, carfentanil's major metabolic pathways involve
    Language English
    Publishing date 2023-04-17
    Publishing country United States
    Document type Journal Article
    ISSN 2575-9108
    ISSN (online) 2575-9108
    DOI 10.1021/acsptsci.3c00031
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  10. Article: Development of an Effective Monoclonal Antibody against Heroin and Its Metabolites Reveals Therapies Have Mistargeted 6-Monoacetylmorphine and Morphine over Heroin.

    Lee, Jinny Claire / Eubanks, Lisa M / Zhou, Bin / Janda, Kim D

    ACS central science

    2022  Volume 8, Issue 10, Page(s) 1464–1470

    Abstract: The opioid epidemic is a global public health crisis that has failed to abate with current pharmaceutical treatments. Moreover, these FDA-approved drugs possess numerous problems such as adverse side effects, short half-lives, abuse potential, and ... ...

    Abstract The opioid epidemic is a global public health crisis that has failed to abate with current pharmaceutical treatments. Moreover, these FDA-approved drugs possess numerous problems such as adverse side effects, short half-lives, abuse potential, and recidivism after discontinued use. An alternative treatment model for opioid use disorders is immunopharmacotherapy, where antibodies are produced to inhibit illicit substances by sequestering the drug in the periphery. Immunopharmacotherapeutics against heroin have engaged both active and passive vaccines targeting heroin's metabolites, 6-monoacetylmorphine (6-AM) and morphine, since decades of research have stated that heroin's psychoactive and lethal effects are mainly attributed to these compounds. However, concerted efforts to develop effective immunopharmacotherapies against heroin abuse have faced little clinical advancement, suggesting a need for reassessing drug target selection. To address this issue, four unique monoclonal antibodies were procured with distinct affinity to either heroin, 6-AM, or morphine. Examination of these antibodies through
    Language English
    Publishing date 2022-10-06
    Publishing country United States
    Document type Journal Article
    ISSN 2374-7943
    ISSN 2374-7943
    DOI 10.1021/acscentsci.2c00977
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