July 2018 News, Updates and Hot Topics

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July 2018

News, Updates and Hot Topics


Database release 2018.3:

Our third database release of the year, 2018.3, is now available. This update contains the following new features and content changes:

  • Updates across several target classes.
  • The existing Antimalarial targets family has been updated with 5 new P. falciparum (3D7) targets:
    • PfATP4 (Plasmodium falciparum ATPase4)
    • PfDHFR-TS (Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase)
    • PfDXR (Plasmodium falciparum 1-deoxy-D-xylulose 5-phosphate reductoisomerase)
    • PfeEF2 (Plasmodium falciparum elongation factor 2)
    • PfPI4K (Plasmodium falciparum phosphatidylinositol 4-kinase)
  • A new Antimalarial ligands family has been created and contains 30 ligands all tagged as an antimalarial in the database. Of these 30, 20 are new ligands curated for this release.
  • GtoImmuPdb now public

The IUPHAR Guide to IMMUNOPHARMACOLOGY is now at its first public release and is no longer considered a beta version. We will continue to develop the portal and specific immuno interfaces as well as continuing curation towards its official launch in October 2018 (see blog post here


Recent Papers from the Team

We are pleased to point to three.  Two were close in succession, both initially as pre-prints in ChemRxiv and later accepted in ACS Omega.  Both are Open Acess and will be full-text indexed in  PubMed Central and European PubMed Central in due course.

“SynPharm: A Guide to PHARMACOLOGY Database Tool for Designing Drug Control into Engineered Proteins” Ireland et.al.DOI/10.1021/acsomega.8b00659

“Challenges of Connecting Chemistry to Pharmacology: Perspectives from Curating the IUPHAR/BPS Guide to PHARMACOLOGY”  Southan et. al. DOI/10.1021/acsomega.8b00884.

The third has been on the Current Protocols in Bioinformatics website for some months but was only just recently indexed in PubMed as “Accessing Expert-Curated Pharmacological Data in the IUPHAR/BPS Guide to PHARMACOLOGY”  Sharman et. al. PMID 30040201.


Hot Topics

The Guide to PHARMACOLOGY hot topics are new and significant pharmacology, drug discovery and key human genomics papers. These are often communicated to us through our expert subcommittee members. All hot topic papers are listed on the hot topics page on the website (http://www.guidetopharmacology.org/hotTopics.jsp). For a selection, we commission concise commentaries from our expert contacts and these are posted onto our blog (https://blog.guidetopharmacology.org/category/hot-topics/).

Here we summarise the latest hot topic commentaries:

New pharmacological tools reiterate lack of direct connection between Angiotensin 1–7 and the MAS1 GPCR

Comments by Sadashiva S. Karnik (karnicks@ccf.org.uk) and Kalyan Tirupula

A new type of deorphanization conundrum confronted in pairing the GPCR, MAS1 with the hormonal peptide angiotensin 1–7 (Ang1-7) was emphasised in recent IUPHAR reviews… Read more.

Structural details for coupling of the agonist-occupied µ opioid receptor (amongst others) to the Gi protein

Comments by Eamonn Kelly (E.Kelly@bristol.ac.uk) and Katy Sutcliffe

Every few years in the field of receptor pharmacology, a technological advance occurs that drives the field forward in terms of insight and understanding. Over the past couple of years, the cryo-EM technique (the development of which won the 2017 Nobel Prize in Chemistry for Dubochet, Frank, and Henderson) for resolving protein structures… Read more.

Systems Medicine, Disease Maps and the future of Systems Biology

Comments by Steven Watterson (@systemsbiology), University of Ulster

What will Systems Biology look like in the future? Up to now, it has focussed on the development of standards, software tools and databases that enabled us to study the dynamics of physiological function mechanistically. Read more.

Structure of the adenosine-bound human adenosine A1 receptor–Gi complex

Comments by Steve Alexander (@mqzspa)

The A1 adenosine receptor is, for most people, a molecular target they can become conscious of when they block it, which happens frequently. Rapid consumption of higher doses of caffeine, in products like Italian espresso or Turkish coffee, provokes a … Read more.

Commentary on the distinction between Cannabis and cannabinoids

Commentary by Steve Alexander (@mqzspa) & Anthony Davenport

The Cannabis plant is a natural product from which more than 100 apparently unique metabolites (cannabinoids) have been identified. Many of these have been found in human plasma following consumption of Cannabis preparations. Read more.

(Update): From double to triple whammy for BACE1 inhibitors

Comments by Chris Southan (@cdsouthan)

19 June 2018 update. Announced only about a week after the events described below,  yet a third clinical candidate, lanabecestat  (AZD-3293, LY3314814) has also bitten the dust (4).  The two PhIII trials were stopped because they were deemed unlikely to meet their primary endpoints. Read more.

Cryo-EM structure of the adenosine A2A receptor coupled to an engineered heterotrimeric G protein

Comments by Steve Alexander (@mqzspa)

The A2A adenosine receptor is densely expressed in dopamine-rich areas of the brain and in the vasculature. It is the target of an adjunct medication for Parkinson’s Disease, istradefylline in Japan, an A2A receptor antagonist. Read more.

Conformational plasticity in the selectivity filter of the TRPV2 ion channel

Comments by Steve Alexander (@mqzspa)

The TRPV2 ion channel is the less well-characterised relative of the TRPV1 or vanilloid receptor that is activated by capsaicin. TRPV2 channels have many similarities to the TRPV1 channels, in that they are homotetrameric and respond to some of the same ligands (natural products such as cannabinoids) as well as being triggered at elevated temperatures. Read more.

3D structure of the P2X3 receptor bound to a negative allosteric modifier, identifies a binding site that is a target for development of novel therapeutic agents

Comments by Dr. Charles Kennedy, University of Strathclyde

Negative allosteric modulators (NAMs) are of great interest in drug development because they offer improved scope for the production of receptor antagonists with enhanced subtype-selectivity. Indeed, many NAMs are already on the market or undergoing clinical trials. NAMs act byRead more.

3D structures of the closed acid-sensing ion channel (ASIC) shed light on the activation mechanism of these neuronal ion channels

Comments by Stephen Kellenberger, Université de Lausanne, Switzerland

ASICs are potential drug targets of interest. Their activation mechanism has however remained elusive. ASICs are neuronal, proton-gated, sodium-permeable channels that are expressed in the central and peripheral nervous system of vertebrates. Read more.

Engineered mini G proteins provide a useful tool for studying the activation of GPCRs in living cells

Comments by Shane C. Wright and Gunnar Schulte, Karolinska Institute

In order to stabilize the GPCR-G protein complex, an agonist must be bound to the receptor and the alpha subunit of the heterotrimer must be in a nucleotide-free state. Read more.

Unexplored therapeutic opportunities in the human genome

Comments by Chris Southan, IUPHAR/BPS Guide to PHARMACOLOGY, @cdsouthan

Contemporary drug discovery is dominated by two related  themes. The first of these is target validation upon which the sustainability of pharmaceutical R&D (in both the commercial and academic sectors) crucially depends. Read more.


Publications

Ireland SM, Southan C, Dominguez-Monedero, Harding SD, Sharman JL, Davies JD. (2018). SynPharm: A Guide to PHARMACOLOGY Database Tool for Designing Drug Control into Engineered Proteins. ACS Omega, 3 (7), pp 7993–8002, doi: 10.1021/acsomega.8b00659.

Southan C, Sharman JL, Faccenda E, Pawson AJ, Harding SD, Davies JA. (2018). Challenges of Connecting Chemistry to Pharmacology: Perspectives from Curating the IUPHAR/BPS Guide to PHARMACOLOGY. ACS Omega, 3 (7), pp 8408–8420, doi: 10.1021/acsomega.8b00884.

Davenport AP, Kuc RE, Southan C, Maguire JJ. (2018). New drugs and emerging therapeutic targets in the endothelin signaling pathway and prospects for personalized precision medicine. Physiol. Res., (Suppl. 1): S37-S54, doi: 10.1021/acsomega.8b00659. [PMID:29947527]

 

Reviews

Caraci F, Calabrese F, Molteni R, Bartova L, Dold M, Leggio GM, Fabbri C, Mendlewicz J, Racagni G, Kasper S, Riva MA, Drago F. (2018) International Union of Basic and Clinical Pharmacology CIV: The Neurobiology of Treatment-resistant Depression: From Antidepressant Classifications to Novel Pharmacological Targets. Pharmacol Rev. 70: 475-504. [PMID:29884653]


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Hot topic: Direct activation of neuronal KV7 channels by GABA and gabapentin – a novel mechanism for reducing neuronal excitability

The potassium channels KV7.2-KV7.5 (KCNQ2-5; GtoPdb target IDs 561-564) regulate neuronal excitability in the mammalian nervous system. The best characterised neuronal KV7 channels give rise to the M current (1) and are mediated predominantly by hetero-tetramers of KV7.2 and KV7.3 subunits (2). Established anticonvulsant agents such as retigabine are known to dampen neuronal excitability by activating neuronal KV7 channels. A tryptophan in the S5 transmembrane region of neuronal KV7 channels is essential for retigabine sensitivity with KV7.3 channels particularly sensitive. Importantly, this residue is not present in the cardiac KV7.1 (KCNQ1) channel, reducing the potential for cardiac side effects.

Now, a pair of studies (3, 4) has shown that this same region of the channel also contributes to a high affinity binding site for GABA and related metabolites (3). GABA activates channels comprised of KV7.3 and KV7.5, including heteromeric KV7.2/7.3 channels, with high potency but low efficacy. GABA does not, however, activate KV7.2 or KV7.4 homomeric channels or cardiac KV7.1 channels. The synthetic anticonvulsant and antinociceptive agent gabapentin activates the same KV7 subunits, although pregabalin does not, despite the overlapping therapeutic efficacy of these two compounds (4).

These results are of considerable pharmacological interest. They suggest a novel mechanism for GABA in regulating neuronal excitability through activation of KV7 channels. They indicate that both GABA and gabapentin will interfere with the action of therapeutically useful activators of KV7 channels such as retigabine. However, perhaps of most value given the relative difficulty in identifying potassium channel openers compared to blockers (5), this work identifies a new chemical class of potential therapeutic activators of neuronal KV7 channels that target an identified region of these channels.

Comments by Emma L. Veale (@Ve11Emma) and Alistair Mathie (@AlistairMathie)

(1) Brown, D.A. & Adams P.R. (1980). Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone. Nature, 283. 673-676. [PMID: 6965523].

(2) Wang H.S. et al. (1998). KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science, 282. 1890-1893. [PMID: 9836639].

(3) Manville R.W. et al. (2018). Direct neurotransmitter activation of voltage-gated potassium channels. Nature Commun., 9(1). 1847. [PMID: 29748663].

(4) Manville R.W. & Abbott G. (2018). Gabapentin is a potent activator of KCNQ3 and KCNQ5 potassium channels. Mol. Pharmacol., doi: 10.1124/mol.118.112953. [PMID: 30021858].

(5) Liin, S.I. et al. (2018). Biaryl sulfonamide motifs up- or down-regulate ion channel activity by activating voltage sensors. J. Gen. Physiol., doi: 10.1085/jgp.201711942. [PMID: 30002162].

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Hot topic: New pharmacological tools reiterate lack of direct connection between Angiotensin 1–7 and the MAS1 GPCR

A new type of deorphanization conundrum confronted in pairing the GPCR, MAS1 with the hormonal peptide angiotensin 1–7 (Ang1-7) was emphasised in recent IUPHAR reviews (1, 2). More evidence for disconnection between Ang1-7 and MAS1 is presented in the recent paper by Gaidarov et al. (3). Ang1-7 is produced by ACE2 or neutral endopeptidase by cleavage of a single amino acid, phenylalanine 8, from angiotensin II (AngII), the major renin angiotensin system hormone. MAS1 was described as the primary receptor for Ang1-7 in regulating diverse biological activities, including vasodilatory, cardio-protective, antithrombotic, antidiuretic and antifibrotic effects (4). These activities are lost in tissues of MAS1-deficient animals, producing striking phenotypes observed in the cardiovascular, renovascular, nervous and reproductive systems. Vast physiological responses to Ang1-7 studied in MAS1-deficient animals serve as the most compelling argument in favor of Ang1-7 pairing with MAS1. However, support for a direct interaction of Ang1-7 with MAS1 lack demonstration of classical G protein signaling and desensitization response to Ang1-7, as well as a lack consensus on confirmatory molecular pharmacological analyses (1, 2).

MAS1-selective small molecule agonists and antagonists from Arena Pharmaceuticals have aided mechanistic study of signaling dynamics in recombinant MAS1 expressing cells. Gaidarov et al. systematically tested efficacy of MAS1-selective non-peptide agonists and antagonists in GPCR signaling and also in signaling-pathway independent assay platforms [3]. Arena Pharmaceutical’s non-peptide ligands modulated G protein-dependent and independent pathways through MAS1, including Gq and Gi pathways, 35S-GTPɣS binding, β-arrestin recruitment, Erk1/2 and Akt phosphorylation, arachidonic acid release, and receptor internalization. Moreover, non-peptide agonists produced robust responses in dynamic mass redistribution (DMR) assays that provide a pathway-agnostic cellular response. The Ang1-7 peptide obtained from multiple sources was inert. In the cell-free assay for G protein coupled MAS1, 35S-GTPɣS binding was undetected in the presence of Ang1–7 suggesting lack of direct interaction with MAS1.

To reject the in vivo analysis based MAS1 pairing with Ang1-7 would still be premature based on the conclusions of Gaidarov et al. (and similar papers cited in ref. #2). MAS1 pairing with Ang1-7 should be considered in the context of type 1 and type 2 errors originally described by Neyman and Pearson (5) and recently revisited (6). Type 1 errors are experiments causing rejection of a null hypothesis which may be true. Type 2 errors are experiments insufficient to reject a flawed null hypothesis. Experiments need to be designed to test the validity of MAS1 functions modulated in vivo by Arena Pharmaceutical ligands rather than simply failing to find pairing with Ang1-7. Involvement of additional GPCRs as “Ang1-7 receptors” or signalosome mechanisms that can link Ang1-7 with MAS1 deserve consideration (7).

Comments by Sadashiva S. Karnik (karniks@ccf.org.us) and Kalyan Tirupula

References

  1. Karnik SS, Singh KD, Tirupula K, Unal H. (2017) Significance of angiotensin 1-7 coupling with MAS1 receptor and other GPCRs to the renin-angiotensin system: IUPHAR Review 22. Br J Pharmacol. 174: 737-753. doi: 10.1111/bph.13742. Review. PMID: 28194766
  2. Karnik SS, Unal H, Kemp JR, Tirupula KC, Eguchi S et al. (2015) International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli [corrected]. Pharmacol Rev 67: 754-819. PMID: 26315714
  3. Gaidarov I, Adams J, Frazer J, Anthony T, Chen X et al. (2018) Angiotensin (1-7) does not interact directly with MAS1, but can potently antagonize signaling from the AT1 receptor. Cell Signal 50: 9-24. PMID: 29928987
  4. Bader M, Alenina N, Andrade-Navarro MA, Santos RA (2014). MAS and its related G protein-coupled receptors, Mrgprs. Pharmacol Rev. 66: 1080–1105. PMID: 25244929
  5. Neyman, J. and Pearson, E.S. (1928). On the use and interpretation of certain test criteria for the purposes of statistical inference. Part I and Part II. Biometrika 20A, 175–240.
  6. Lew MJ (2006). Principles: when there should be no difference–how to fail to reject the null hypothesis. Trends Pharmacol Sci. 27:274-278. PMID: 16595154
  7. Tirupula KC, Zhang D, Osbourne A, Chatterjee A, Desnoyer R, Willard B et al. (2015). MAS C-terminal tail interacting proteins identified by mass spectrometry-based proteomic approach. PLoS One 10: e0140872. PMID: 26484771
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Hot Topic: Structural details for coupling of the agonist-occupied µ opioid receptor (amongst others) to the Gi protein

Every few years in the field of receptor pharmacology, a technological advance occurs that drives the field forward in terms of insight and understanding. Over the past couple of years, the cryo-EM technique (the development of which won the 2017 Nobel Prize in Chemistry for Dubochet, Frank, and Henderson) for resolving protein structures at near atomic resolution has been highlighted as one such approach. Now some of the first papers applying this methodology to G protein-coupled receptors (GPCRs) are beginning to appear. The strength of this approach for GPCRs is revealed in the recent paper by Koehl et al. (1) showing the detailed structure of the agonist-bound µ opioid receptor (GtoPdb target ID 139) coupled to the Gi subtype of G protein. DAMGO (GtoPdb ligand ID 1647), the agonist used in the study, is a selective and efficacious peptide agonist at the µ receptor and is used in many studies as the standard µ receptor agonist. The structure of the DAMGO-µ receptor-Gi complex shows some interesting and unexpected detail, for example, that the binding pocket for Gi at the base of the receptor is smaller, and the outswing of the lower end of TMD VI smaller, than that for GPCRs that couple primarily to Gs proteins.

Apart from the obvious benefits for future drug development at µ receptor, the full impact of the cryo-EM approach for µ receptor structure/function is likely to be felt more in the future, as we can no doubt look forward to the appearance of µ receptor/signalling protein structures with partial agonists as well as biased agonists, and the structure of ligand-bound µ receptor interacting with GRKs or arrestin proteins. The speed at which this field is moving is already breathtaking – in the issue of Nature carrying the DAMGO-µ receptor-Gi cryo-EM report, there are others detailing the structure of activated rhodopsin-Gi (2), adenosine activated adenosine A1-Gi (3) and agonist-activated 5HT1B-Go (4). Recently also the structure of the Class B GLP-1 receptor in complex with a biased ligand and Gs was reported (5). Many more structures of such complexes are likely to follow over the next couple of years, with a corresponding leap forward in our understanding of the structure and function of GPCRs. There are still challenges however; as Koehl and colleagues point out in their groundbreaking paper (1), the nature of the initial interactions of G proteins and other signalling proteins with GPCRs, and the identity of the possibly novel receptor conformations that exist at these early time points in complex formation, remain considerable challenges for both X-ray crystallography and cryo-EM techniques.

Comments by Eamonn Kelly (E.Kelly@bristol.ac.uk) and Katy Sutcliffe

(1) Koehl A. et al. (2018). Structure of the μ-opioid receptor–Gi protein complex. Nature, 558. 547–552. [PMID: 29899455]

(2) Kang Y. et al. (2018). Cryo-EM structure of human rhodopsin bound to an inhibitory G protein. Nature, 558. 553-558. [PMID: 29899450]

(3) Draper-Joyce C.J. et al. (2018). Structure of the adenosine-bound human adenosine A1 receptor–Gi complex. Nature, 558. 559–563. [PMID: 29925945]

(4) García-Nafría J. et al. (2018). Cryo-EM structure of the serotonin 5-HT1B receptor coupled to heterotrimeric Go. Nature, 558. 620-623. [PMID: 29925951]

(5) Liang Y.L. et al. (2018). Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor-Gs complex. Nature, 555. 121-125. [PMID: 29466332]

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Hot Topic: Systems Medicine, Disease Maps and the future of Systems Biology

What will Systems Biology look like in the future? Up to now, it has focussed on the development of standards, software tools and databases that enabled us to study the dynamics of physiological function mechanistically. However as these tools and technologies have matured, the focus of the systems biology research community has moved towards how they can best be interconnected and exploited to develop our understanding of health and disease across whole cells, tissues, organs, organisms. This version 2.0 of systems biology, will build on the existing technologies to create resources that are more intuitive, more accurate, more accessible and are easier to use for anyone engaged with research.

Disease maps describe the interactions and pathways that are perturbed from healthy physiological function in disease pathophysiology. The Disease Maps consortia, spearheaded by the Luxembourg Centre for Systems Biomedicine, the Institut Curie and the European Institute for Systems Biology and Medicine, are developing rich resources to enable us to understand how healthy function is perturbed across different scales. These include from the molecular to the organismal, and that embed individually perturbed pathways in a wider intra- and inter-cellular network so that the systems and systemic impact can be more easily investigated [1].   Each disease topic is the focus of a community of clinical, laboratory and systems biology expertise and the consortia is organised as a community of communities with the following adopted principles:-

  • Central integration of in vivo and in vitro disease experts across diseases
  • Close integration of pathway mapping and modeling expertise
  • Regular sharing of best practice and expertise across diseases

The consortia embrace open access, standard formats, modularity, consistency of quality and best practices in the field. It is anticipated that this work will deliver resources that can support comprehensive programmes of systems medicine by including the following:

  • Dedicated trusted reference resources describing disease mechanisms that facilitate advanced data interpretation, hypothesis generation, and hypothesis prioritisation.
  • Tools for the study of co- and multi-morbidities, which can deliver refined biomarkers for improved clinical diagnostics.
  • Tools for the study of systems pharmacology that suggest drug repositioning and multi-drug intervention strategies.
  • Novel insights into disease subclassification supporting the development of next-generation disease ontologies.
  • Supporting the design and prototyping of new clinical decision-making strategies.

The Disease Maps consortia thus want to accelerate the development of Systems Biology 2.0 and the roadmap presented in this paper describes how it can be steered towards translational utility.

Comments by Steven Watterson (@systemsbiology), University of Ulster

[1]. Mazein A, Ostaszewski M, Kuperstein I, Watterson S, Le Novère N, Lefaudeux D, De Meulder B, Pellet J, Balaur I, Saqi M, Nogueira MM, He F, Parton A, Lemonnier N, Gawron P, Gebel S, Hainaut P, Ollert M, Dogrusoz U, Barillot E, Zinovyev A, Schneider R, Balling R and Auffray C (2018) Systems medicine disease maps: community-driven comprehensive representation of disease mechanisms, NPG Systems Biology and Applications 4:21. [PMID 29872544]

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Hot topic: Structure of the adenosine-bound human adenosine A1 receptor–Gi complex

The A1 adenosine receptor is, for most people, a molecular target they can become conscious of when they block it, which happens frequently. Rapid consumption of higher doses of caffeine, in products like Italian espresso or Turkish coffee, provokes a rapid, transient increase in heart rate and a noticeable increase in limb tremor. As the most widely consumed psychoactive substance, caffeine has these effects through blockade of the A1 adenosine receptor, which is found on cardiomyocytes and the peripheral nerve terminals of the sympathetic nervous system (as well as many other locations), leading to an increase in cardiac contractility and noradrenaline release, respectively.

In this report, a 3.6 Å structure of the receptor complexed with the endogenous agonist, adenosine, in the presence of the heterotrimeric G12 protein has been resolved by cryo-EM. As expected, there are differences in conformation compared to the previously-reported antagonist-bound receptor, principally in TM1 and TM2. There are also differences compared to the structure reported for the Gs-coupled, agonist-bound beta2-adrenoceptor.

Comments by Steve Alexander (@mqzspa)

(1) Draper-Joyce C.J. et al. (2018). Structure of the adenosine-bound human adenosine A1 receptor–Gi complex. Nature, 558. 559–563. [PMID: 29925945]

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Database release 2018.3

Our third database release of the year, 2018.3, is now available. This update contains the following new features and content changes:

Content updates

GPCRs:
Adenosine receptors
Chemokine receptors
Cholecystokinin receptors
Dopamine receptors
Ghrelin receptors
Opioid receptors
GPR55 receptors

NHRs:
MRetinoic acid receptor

Channels:
Transient Receptor Potential channels
voltage-gated sodium channels

Enzymes:
Guanylyl cyclases (GCs)
Janus kinase (JakA) family
Mitogen-activated protein kinases (MAP kinases)
Nitric oxide synthases

Catalytic Receptors:
Natriuretic peptide receptor family

Transporters:
ABCG subfamily
Monoamine transporter subfamily

Others:
CD molecules

Anti-malarial data

The existing Antimalarial targets family has been updated with 5 new P. falciparum (3D7) targets:

  • PfATP4 (Plasmodium falciparum ATPase4)
  • PfDHFR-TS (Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase)
  • PfDXR (Plasmodium falciparum 1-deoxy-D-xylulose 5-phosphate reductoisomerase)
  • PfeEF2 (Plasmodium falciparum elongation factor 2)
  • PfPI4K (Plasmodium falciparum phosphatidylinositol 4-kinase)

A new Antimalarial ligands family has been created and contains 30 ligands all tagged as an antimalarial in the database. Of these 30, 20 are new ligands curated for this release.

New website features

GtoImmuPdb now public

The IUPHAR Guide to IMMUNOPHARMACOLOGY is now at its first public release and is no longer considered a beta version. We will continue to develop the portal and specific immuno interfaces as well as continuing curation towards its official launch in October 2018. This will be at the BPS Immunopharmacology: Challenges, opportunities and research tools meeting in Edinburgh, 1st-2nd October 2018.

Disease Summary Pages

The disease summary pages have been modified to improve the payout of target information and provide links to help to understand terms and symbols. The display of associated ligand is now in a sortable table and the comments section includes bioactivity comments where present. We have also include links to the specific clinical data or bio-activity tabs on ligand summary pages.

Posted in Database updates, Guide to Immunopharmacology, Guide to Malaria Pharmacology