bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactive adsorption of Safranin O: surface – pore diffusion modeling and degradation study
Authors: Sharma Komal , Vyas Raj K. , Singh Kailash , Dalai Ajay K.
Published: September 2019

Granular activated carbon was doped with iron (Fe-AC) and was used to study the removal of Safranin O (SO) using the Fe-AC/H2O2 system for reactive adsorption and Fe-AC for adsorption. Fe-AC and H2O2 doses were optimized to obtain maximum removal of SO. Maximum removal was found to be 96.1% after 5 h using 1.0 g/L Fe-AC and 5.0 mM hydrogen peroxide doses for 10 mg/L initial SO concentration. Kinetic study suggested the suitability of the pseudo-first-order model for reactive adsorption. The Langmuir isotherm explained well the sorption of SO onto Fe-AC. Parallel-pore-reactive adsorption model was applied and validated. By fitting the experimental data to the model, it is observed that the surface reaction rate coefficient, kr, was found to be five times that of the apparent rate constant, kapp. Parameters such as the external liquid film mass transfer coefficient, macro-pore and micro-pore diffusivities were estimated by regression analysis. Pore diffusion and surface reaction were found to be rate controlling for adsorption and reactive adsorption, respectively. An oxidative degradation of SO took place via hydroxylation and ring cleavage processes.
Doğrudan Yabancı Yatırım Girişlerinde Açıklanmış Karşılaştırmalı Üstünlük Analizi
Authors: Kılıçarslan Zerrin
Published: September 2019

Rekabet gücü yüksek olan
sektörleri belirlemek için Balassa endeksi olarak da bilinen açıklanmış
karşılaştırmalı üstünlük (RCA) endeksi kullanılmaktadır.  Bu endeksten hareketle doğrudan yabancı
yatırım çekmek üzere hedef sektörleri belirlemek veya doğrudan yabancı yatırım
için konumların karşılaştırmalı üstünlüğünü analiz etmek için kullanılacak bir
yöntem olarak doğrudan yabancı yatırımda açıklanmış karşılaştırmalı üstünlük
endeksi Loewendahl ve Barklie (2018) tarafından geliştirilmiştir. Bu çalışmada
Türkiye’nin ve OECD ülkelerinin doğrudan yabancı yatırımlardaki açıklanmış
karşılaştırmalı üstünlüklerinin sektörel olarak belirlenmesi amaçlanmıştır. Bu
amaçla Loewendahl ve Barklie (2018) tarafından geliştirilen endeksi
kullanılmıştır. Türkiye’nin doğrudan yabancı yatırımlarda açıklanmış
karşılaştırmalı üstünlüğe sahip olduğu sektörler belirlenmiştir. RCA-FDI endeksi
değerleri 2013 ve 2017 yılları için ayrı ayrı hesaplanmış ve Türkiye’nin
doğrudan yabancı yatırımlardaki açıklanmış karşılaştırmalı üstünlüklerindeki
değişim açıklanmıştır. Ayrıca OECD ülkeleri için temel ekonomik faaliyet
alanlarında endeksi hesaplanmıştır. Türkiye için hesaplanan endeksi değerlerine
göre ana faaliyet alanları içerisinde “tarım, ormancılık ve balıkçılık”
sektöründe güçlü karşılaştırmalı üstünlük, “imalat” sektöründe zayıf
karşılaştırmalı üstünlük, “elektrik, gaz, buhar ve iklimlendirme temini”nde
güçlü karşılaştırmalı üstünlük, “su tedariki, kanalizasyon, atık yönetimi ve
iyileştirme faaliyetleri”nde zayıf karşılaştırmalı üstünlük, “inşaat”ta zayıf
karşılaştırmalı üstünlük ortaya çıkmıştır. Bununla birlikte “hizmetler”
sektöründe ise rekabet avantajı bulunmamaktadır. Türkiye’nin en güçlü
karşılaştırmalı üstünlüğünün olduğu sektörler “kütüphaneler, arşivler, müzeler
ve diğer kültürel faaliyetler” ve “kara taşımacılığı ve boru hatları taşımacılığı”dır.
OECD ülkelerinde güçlü karşılaştırmalı üstünlüğe sahip olan ülke sayısının en
fazla olduğu sektör “tarım, ormancılık ve balıkçılık”tır. Karşılaştırmalı
dezavantaja sahip olan ülke sayısının en fazla olduğu sektör ise “madencilik ve
taşocakçılığı”dır. “İmalat” sektöründe ise hiçbir ülke güçlü ve orta
karşılaştırmalı üstünlüğe sahip bulunmamaktadır.
Drug Repurposing Screen Identifies Novel Classes of Drugs with Anticancer Activity in Mantle Cell Lymphoma
Authors: Han Chengwu , Yu Xueying , Zhang Chunxia , Cai Ying , Cao Yongyue , Wang Sijie , Shen Jun
Published: September 2019

Aim and Objective:

Mantle Cell Lymphoma (MCL) is typically an aggressive and rare
disease with poor prognosis, therefore new effective therapeutics are urgently needed. Drug
repurposing for cancer treatment is becoming increasingly more attractive as an alternative
approach to discover clinically approved drugs that demonstrate antineoplastic effect. The
objective of this study was to screen an approved drug library and identify candidate compounds
with an antineoplastic effect in MCL cells using High-Throughput Screening (HTS) technique.

Materials and Methods:

Using the HTS technique, nearly 3,800 clinically approved drugs and
drug candidates were screened in Jeko and Mino MCL cell lines. We also demonstrated the
selectivity window of the candidate compounds in six normal cell lines. Further validations were
performed in caspase-3/7 apoptosis assay and three-dimensional (3D) multicellular aggregates
model using Z138 cell line.

Results:

We identified 98 compounds showing >50% inhibition in either MCL cell line screened,
they were distributed across eight unique therapeutic categories and have different mechanisms of
action (MOA). We selected alisertib, carfilzomib, pracinostat and YM155 for further validation
based on their antiproliferative activity in two MCL cell lines, selectivity to normal cell lines, and
drug developing stages in terms of clinical research. Alisertib and carfilzomib showed
antiproliferative effect on MCL cell with EC50 = 6 nM and >100-fold selectivity to normal cell
lines, especially for alisertib which demonstrated >1000-fold selectivity to 5 out of 6 normal cell
lines. Pracinostat and YM155 had potency of 11 and 12 nM in MCL cell with >20-fold selectivity
to normal cell lines. All four compounds had been tested in caspase-dependent apoptosis assay. We
further validated and demonstrated their anti-MCL effect on cell proliferation and (3D)
multicellular aggregates model using Z138 cell line.

Conclusion:

This is the first study to examine such a large library of clinically approved
compounds for the identification of novel drug candidates for MCL treatment, the results could be
rapidly translated into clinical practice in patients with MCL.
Clinical Features of Systemic Lupus Erythematosus in Tunisian Males
Authors: Sayhi Sameh , Achour Tayssir B. , Mezri Sameh , Hamdi Mohamed S. , Nour Gueddiche , Bilel Arfaoui , Abdelhafidh Nadia B. , Ajili Faida , Louzir Bassem
Published: September 2019

Purpose:

Systemic Lupus Erythematosus (SLE) in males is rare. Clinical and biological
features, as well as, the outcome may differ comparatively to female patients. The purpose of our
study is to define these clinical and biological features in Tunisian male patients presenting SLE.

Methods:

A mono-centric, retrospective and descriptive study of 96 patients followed for SLE out
of which 21 are males. A comparative study was then performed between male and female patients
groups.

Results:

Sex-ratio female/male was 3.6/1, the average age at diagnosis of SLE was 37.8±14 years.
The most frequently noted clinical manifestations were: skin involvement (81%), renal involvement
(71.4%) and joint damage (66.7). We observed a significant difference in clinical features between
male and female patients (21 males and 76 females): renal failure (52% vs. 71.4%), serositis
(23.8% vs. 2.7%), peripheral neuropathy (19% vs. 4%) and lung interstitial disease (14.3% vs.
1.3%). No significant difference was found in the positivity of serum antibodies between the two
groups. Fifteen male patients (71.4%) had a SLEDAI score greater than or equal to 11, referring to
high/very high disease activity. Out of the 32 patients who developed infectious complications during
the course of the disease, 11 were male (52.4% of males). Concerning the male group, complete
remission was observed in 10 patients (47.6%), while 10 others presented persistent sequella. We
observed one death in the male group secondary to infective acute respiratory failure.

Conclusion:

SLE in male patients is rare and associated with poor prognosis. Disparity was observed
in clinical and biological features as well as outcome in the different studies. In our study,
we concluded that male lupus is more severe.
Design and Molecular Docking Studies of Some 2,3 Di-Substituted Quinazolin-4-One Analogues Against Staphylococcus aureus UDG
Authors: Bhavesh Amrute B. , Rakesh Amrutkar D. , Santosh Tambe R.
Published: September 2019

Background:

In this present investigation, some 2, 3 disubstituted-quinazolin-4-one derivatives
are designed and docked against chain A and chain B of (3WDF) receptor.

Methods:

The heterocyclic fused rings quinazolinone have drawn a great attention owing to their
expanded applications in the field of pharmaceutical chemistry. The diverse range of molecules
with quinazoline/quinazolinone moieties have been reported to exhibit a broad spectrum of biological
activities.

Results:

The results designate that the quinazolinone ring forms hydrophobic and hydrogen bond
contacts with ASN 127 A, ALA 126 A, and SER 83 B, SER 183 B amino acid residue.

Conclusion:

: Molecular docking is safe and straightforward to use tool which facilitates in investigating,
interpreting, enplaning and identification of molecular properties using 3D structures.
Pembrolizumab-Induced Seronegative Arthritis and Fasciitis in a Patient with Lung Adenocarcinoma
Authors: Kobak Senol
Published: September 2019

Background:

Immune checkpoint inhibitors (CPIs) are new promising anti-cancer drugs that
block negative costimulation of T-cells leading to an enhanced anti-tumor immune response. Pembrolizumab,
an a monoclonal antibody, targeting the programmed cell death protein 1 (PD-1) pathway. CPIs
have been associated with a number of immune-related adverse events (AEs), including musculoskeletal
and rheumatic disease.

Objective:

To present a case with lung adenocarcinoma treated with pembrolizumab, which developed inflammatory
arthritis and fasciitis.

Case Report:

A 73-year-old male patient was referred to the rheumatology outpatient clinic with complaints
of pain in the pretibial area, pain and swelling in both ankles joints and the right fırst metacarpophalangeal
(MCP) joint. Three months ago he had diagnosed with lung adenocarcinoma and pembrolizumab was started.
Locomotor system complaints were started after receiving two infusions of pembrolizumab. Physical
examination revealed both ankle arthritis, mild edema in the pretibial region, tenderness in the muscles and
arthritis in the right fırst MCP joint. Laboratory examinations showed mild acute phase reactants elevation.
Lower extremity MRI showed diffuse edema in both gastrocnemius muscle and fascia, compatible with
fasciitis. Pembrolizumab-related fasciitis and seronegative arthritis were diagnosed. Low dose corticosteroid
was started and a significant regression was observed in the patient's complaints.

Conclusion:

Inflammatory myositis with fasciitis and inflammatory arthritis in lower extremities appears to
be a new adverse effect of pembrolizumab therapy.
PHARMACEUTICAL WORLD WITH INNOVATIVE APPROACHES-A REVIEW
Authors: RASTOGI HARSH , PURKAYASTHA HRISHAV DAS , TIWARI SHALINI
Published: September 2019

An existing drug in the conventional dosage form is evolution in to novel drug delivery system which can significantly enhances and improves the performance of drug in terms of drug safety, drug efficacy as well as patient compliance. With the help of appropriate novel approaches, an existing drug molecule can get a new life and can be a major advance solution for the problems towards the release of drug at specific site and specific rate. The main aim of novel drug delivery system is to minimize the drug loss and drug degradation which can be achieved by targeting the drug to the site of interest. With the help of soluble or insoluble biodegradable natural and synthetic polymers different novel formulations can be formulated as microparticles, microcapsules, liposomes, neosomes, micelles etc. Targeting is based on active targeting and passive targeting mechanisms for drug release. This review covers the basic information on Novel Drug Delivery Systems (NDDS).
ANTI-INFLAMMATORY EFFECT OF NIGELLA SATIVA OIL ON CHEMORADIATION-INDUCED ORAL MUCOSITIS IN PATIENTS WITH HEAD AND NECK CANCERS
Authors: AMEEN HAZHA ABDULLAH MOHAMMED , MOHAMMED MOHAMMED OMER , KHADIJA MUHAMED AHMED  , REBAZ HAMA-GAREB ALI  , KAMAL AHMED SAEED  , SAAD ABDULRAHMAN HUSSAIN
Published: September 2019

Objective: Oral mucositis (OM) is a common treatment-induced toxicity in patients undergoing radiation or chemoradiation for head and neck cancers (HNC). The study aims to evaluate the anti-inflammatory effect of Nigella sativa (NS) oil in radiation-or chemoradiation-induced OM in HNC patients.

Methods: From Forty HNC patients were randomized to two groups, each of 20 patients. The first group was treated with NS oil mouthwash five times daily, while the second group was treated with the Magic mouthwash and served as a control. All patients received radiotherapy (RT) (60-70 Gy) in 30-35 fractions over 6-7 w with or without chemotherapy. Patients were evaluated once per week to estimate the severity and duration of OM and the salivary levels of IL-6 and TNF-α.

Results: 70% of patients were men and the commonest tumor locations were larynx (47.5%) and pharynx (22.5%) classified as stages III or IV. NS oil significantly reduces RTOG grade and OM severity after 3-4 w of RT, attenuates the elevation in salivary IL-6 and TNF-α production after 3-5 w.

Conclusion: Nigella sativa oil mouthwash have a potential anti-inflammatory activity that may be beneficial in minimizing or preventing radiation-or chemoradiation-induced oral mucositis in patients with head and neck cancer.
5-Hydroxytryptamine receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Andrade Rodrigo , Barnes Nicholas M. , Baxter Gordon , Bockaert Joel , Branchek Theresa , Butler Amy , Cohen Marlene L. , Dumuis Aline , Eglen Richard M. , Göthert Manfred , Hamblin Mark , Hamon Michel , Hartig Paul R. , Hen René , Hensler Julie , Herrick-Davis Katharine , Hills Rebecca , Hoyer Daniel , Humphrey Patrick P. A. , Latté Klaus Peter , Maroteaux Luc , Martin Graeme R. , Middlemiss Derek N. , Mylecharane Ewan , Neumaier John , Peroutka Stephen J. , Peters John A. , Roth Bryan , Saxena Pramod R. , Sharp Trevor , Sleight Andrew , Villalon Carlos M. , Yocca Frank
Published: September 2019

5-HT receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on 5-HT receptors [194] and subsequently revised [176]) are, with the exception of the ionotropic 5-HT3 class, GPCRs where the endogenous agonist is 5-hydroxytryptamine. The diversity of metabotropic 5-HT receptors is increased by alternative splicing that produces isoforms of the 5-HT2A (non-functional), 5-HT2C (non-functional), 5-HT4, 5-HT6 (non-functional) and 5-HT7 receptors. Unique amongst the GPCRs, RNA editing produces 5-HT2C receptor isoforms that differ in function, such as efficiency and specificity of coupling to Gq/11 and also pharmacology [40, 482]. Most 5-HT receptors (except 5-ht1e and 5-ht5b) play specific roles mediating functional responses in different tissues (reviewed by [463, 382]).
Calcitonin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Hay Debbie , Poyner David R. , Walker Christopher S.
Published: September 2019

This receptor family comprises a group of receptors for the calcitonin/CGRP family of peptides. The calcitonin (CT), amylin (AMY), calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on CGRP, AM, AMY, and CT receptors [122, 67]) are generated by the genes CALCR (which codes for the CT receptor) and CALCRL (which codes for the calcitonin receptor-like receptor, CLR, previously known as CRLR). Their function and pharmacology are altered in the presence of RAMPs (receptor activity-modifying proteins), which are single TM domain proteins of ca. 130 amino acids, identified as a family of three members; RAMP1, RAMP2 and RAMP3. There are splice variants of the CT receptor; these in turn produce variants of the AMY receptor [122], some of which can be potently activated by CGRP. The endogenous agonists are the peptides calcitonin, α-CGRP (formerly known as CGRP-I), β-CGRP (formerly known as CGRP-II), amylin (occasionally called islet-amyloid polypeptide, diabetes-associated polypeptide), adrenomedullin and adrenomedullin 2/intermedin. There are species differences in peptide sequences, particularly for the CTs. CTR-stimulating peptide (CRSP) is another member of the family with selectivity for the CT receptor but it is not expressed in humans [87]. olcegepant (also known as BIBN4096BS, pKi~10.5) and telcagepant (also known as MK0974, pKi~9) are the most selective antagonists available, showing selectivity for CGRP receptors, with a particular preference for those of primate origin. CLR (calcitonin receptor-like receptor) by itself binds no known endogenous ligand, but in the presence of RAMPs it gives receptors for CGRP, adrenomedullin and adrenomedullin 2/intermedin.
Acid-sensing (proton-gated) ion channels (ASICs) (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Kellenberger Stephan , Rash Lachlan D. , Schild Laurent
Published: September 2019

Acid-sensing ion channels (ASICs, nomenclature as agreed by NC-IUPHAR [35]) are members of a Na+ channel superfamily that includes the epithelial Na+ channel (ENaC), the FMRF-amide activated channel (FaNaC) of invertebrates, the degenerins (DEG) of Caenorhabitis elegans, channels in Drosophila melanogaster and 'orphan' channels that include BLINaC [46] and INaC [47] that have also been named BASICs, for bile acid-activated ion channels [58]. ASIC subunits contain two TM domains and assemble as homo- or hetero-trimers [34, 31, 5] to form proton-gated, voltage-insensitive, Na+ permeable, channels (reviewed in [33, 57]). Splice variants of ASIC1 [termed ASIC1a (ASIC, ASICα, BNaC2α) [55], ASIC1b (ASICβ, BNaC2β) [13] and ASIC1b2 (ASICβ2) [50]; note that ASIC1a is also permeable to Ca2+] and ASIC2 [termed ASIC2a (MDEG1, BNaC1α, BNC1α) [45, 56, 30] and ASIC2b (MDEG2, BNaC1β) [40]] have been cloned. Unlike ASIC2a (listed in table), heterologous expression of ASIC2b alone does not support H+-gated currents. A third member, ASIC3 (DRASIC, TNaC1) [54], has been identified. A fourth mammalian member of the family (ASIC4/SPASIC) does not support a proton-gated channel in heterologous expression systems and is reported to downregulate the expression of ASIC1a and ASIC3 [1, 32, 24, 39]. ASIC channels are primarily expressed in central and peripheral neurons including nociceptors where they participate in neuronal sensitivity to acidosis. They have also been detected in taste receptor cells (ASIC1-3), photoreceptors and retinal cells (ASIC1-3), cochlear hair cells (ASIC1b), testis (hASIC3), pituitary gland (ASIC4), lung epithelial cells (ASIC1a and -3), urothelial cells, adipose cells (ASIC3), vascular smooth muscle cells (ASIC1-3), immune cells (ASIC1,-3 and -4) and bone (ASIC1-3). A neurotransmitter-like function of protons has been suggested, involving postsynaptically located ASICs of the CNS in functions such as learning and fear perception [25, 36, 63], responses to focal ischemia [59] and to axonal degeneration in autoimmune inflammation in a mouse model of multiple sclerosis [29], as well as seizures [64] and pain [19, 20, 10, 22]. Heterologously expressed heteromultimers form ion channels with differences in kinetics, ion selectivity, pH- sensitivity and sensitivity to blockers that resemble some of the native proton activated currents recorded from neurones [40, 3, 28, 8].
Aquaporins (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Conner Alex C.
Published: September 2019

Aquaporins and aquaglyceroporins are membrane channels that allow the permeation of water and certain other small solutes across the cell membrane, or in the case of AQP6, AQP11 and AQP12A, intracellular membranes, such as vesicles and the endoplasmic reticulum membrane [9]. Since the isolation and cloning of the first aquaporin (AQP1) [10], 12 additional mammalian members of the family have been identified, although little is known about the functional properties of one of these (AQP12A; Q8IXF9) and it is thus not tabulated. The other 12 aquaporins can be broadly divided into three families: orthodox aquaporins (AQP0,-1,-2,-4,-5, -6 and -8) permeable mainly to water, but for some additional solutes [2]; aquaglyceroporins (AQP3,-7 -9 and -10), additionally permeable to glycerol and for some isoforms urea [8], and superaquaporins (AQP11 and 12) located within cells [5]. Some aquaporins also conduct ammonia and/or H2O2 giving rise to the terms 'ammoniaporins' ('aquaammoniaporins') and 'peroxiporins', respectively. Aquaporins are impermeable to protons and other inorganic and organic cations, with the possible exception of AQP1 [8]. One or more members of this family of proteins have been found to be expressed in almost all tissues of the body [reviewed in Yang (2017) [13]]. AQPs are involved in numerous processes that include systemic water homeostasis, adipocyte metabolism, brain oedema, cell migration and fluid secretion by epithelia and loss of function mutations of some human AQPs, or their disruption by autoantibodies further underscore their importance [reviewed by Verkman et al. (2014) [12], Kitchen et al. (2105) [8]]. Functional AQPs exist as homotetramers that are the water conducting units wherein individual AQP subunits (each a protomer) have six transmembrane helices and two half helices that constitute a seventh 'pseudotransmembrane domain' that surrounds a narrow water conducting channel [9]. In addition to the four pores contributed by the protomers, an additional hydrophobic pore exists within the center of the complex [9] that may mediate the transport of gases (e.g. O2, CO2, NO) and cations (the central pore is the proposed transport pathway for cations through AQP1) by some AQPs [4, 6]. Although numerous small molecule inhibitors of aquaporins, particularly APQ1, have been reported primarily from Xenopus oocyte swelling assays, the activity of most has subsequently been disputed upon retesting using assays of water transport that are less prone to various artifacts [3] and they are therefore excluded from the tables [see Tradtrantip et al. (2017) [11] for a review].
Calcium-sensing receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Bikle Daniel , Bräuner-Osborne Hans , Brown Edward M. , Chang Wenhan , Conigrave Arthur , Hannan Fadil , Leach Katie , Riccardi Daniela , Shoback Dolores , Ward Donald T. , Yarova Polina
Published: September 2019

The calcium-sensing receptor (CaS, provisional nomenclature as recommended by NC-IUPHAR [44]) responds to multiple endogenous ligands, including extracellular calcium and other divalent/trivalent cations, polyamines and polycationic peptides, L-amino acids (particularly L-Trp and L-Phe), glutathione and various peptide analogues, ionic strength and extracellular pH (reviewed in [74]). While divalent/trivalent cations, polyamines and polycations are CaS receptor agonists [14, 106], L-amino acids, glutamyl peptides, ionic strength and pH are allosteric modulators of agonist function [34, 44, 58, 104, 105]. Indeed, L-amino acids have been identified as "co-agonists", with both concomitant calcium and L-amino acid binding required for full receptor activation [143, 51]. The sensitivity of the CaS receptor to primary agonists is increased by elevated extracellular pH [17] or decreased extracellular ionic strength [105]. This receptor bears no sequence or structural relation to the plant calcium receptor, also called CaS.
SLC22 family of organic cation and anion transporters (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Hagenbuch Bruno
Published: September 2019

The SLC22 family of transporters is mostly composed of non-selective transporters, which are expressed highly in liver, kidney and intestine, playing a major role in drug disposition. The family may be divided into three subfamilies based on the nature of the substrate transported: organic cations (OCTs), organic anions (OATs) and organic zwiterrion/cations (OCTN). Membrane topology is predicted to contain 12 TM domains with intracellular termini, and an extended extracellular loop at TM 1/2.
SLC28 and SLC29 families of nucleoside transporters (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Hammond James R.
Published: September 2019

Nucleoside transporters are divided into two families, the sodium-dependent, concentrative solute carrier family 28 (SLC28) and the equilibrative, solute carrier family 29 (SLC29). The endogenous substrates are typically nucleosides, although some family members can also transport nucleobases and organic cations.
ABCD subfamily of peroxisomal ABC transporters (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Kemp Stephan
Published: September 2019

Peroxisomes are indispensable organelles in higher eukaryotes. They are essential for the oxidation of a wide variety of metabolites, which include: saturated, monounsaturated and polyunsaturated fatty acids, branched-chain fatty acids, bile acids and dicarboxylic acids [3]. However, the peroxisomal membrane forms an impermeable barrier to these metabolites. The mammalian peroxisomal membrane harbours three ATP-binding cassette (ABC) half-transporters, which act as homo- and/or heterodimers to transport these metabolites across the peroxisomal membrane.
Acetylcholine receptors (muscarinic) (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Birdsall Nigel J. M. , Bradley Sophie , Brown David A. , Buckley Noel J. , Challiss R.A. John , Christopoulos Arthur , Eglen Richard M. , Ehlert Frederick , Felder Christian C. , Hammer Rudolf , Kilbinger Heinz J. , Lambrecht Günter , Langmead Chris , Mitchelson Fred , Mutschler Ernst , Nathanson Neil M. , Schwarz Roy D. , Tobin Andrew B. , Valant Celine , Wess Jurgen
Published: September 2019

Muscarinic acetylcholine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Muscarinic Acetylcholine Receptors [45]) are GPCRs of the Class A, rhodopsin-like family where the endogenous agonist is acetylcholine. In addition to the agents listed in the table, AC-42, its structural analogues AC-260584 and 77-LH-28-1, N-desmethylclozapine, TBPB and LuAE51090 have been described as functionally selective agonists of the M1 receptor subtype via binding in a mode distinct from that utilized by non-selective agonists [243, 242, 253, 155, 154, 181, 137, 11, 230]. There are two pharmacologically characterised allosteric sites on muscarinic receptors, one defined by it binding gallamine, strychnine and brucine, and the other defined by the binding of KT 5720, WIN 62,577, WIN 51,708 and staurosporine [161, 162].
SLC23 family of ascorbic acid transporters (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: May James M.
Published: September 2019

Predicted to be 12 TM segment proteins, members of this family transport the reduced form of ascorbic acid (while the oxidized form may be handled by members of the SLC2 family (GLUT1/SLC2A1, GLUT3/SLC2A3 and GLUT4/SLC2A4). phloretin is considered a non-selective inhibitor of these transporters, with an affinity in the micromolar range.
Free fatty acid receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Briscoe Celia , Brown Andrew , Holliday Nick , Jenkinson Stephen , Milligan Graeme , Monaghan Amy E. , Stoddart Leigh
Published: September 2019

Free fatty acid receptors (FFA, nomenclature as agreed by the NC-IUPHAR Subcommittee on free fatty acid receptors [111, 24]) are activated by free fatty acids. Long-chain saturated and unsaturated fatty acids (including C14.0 (myristic acid), C16:0 (palmitic acid), C18:1 (oleic acid), C18:2 (linoleic acid), C18:3, (α-linolenic acid), C20:4 (arachidonic acid), C20:5,n-3 (EPA) and C22:6,n-3 (docosahexaenoic acid)) activate FFA1 [8, 50, 60] and FFA4 receptors [41, 48, 90], while short chain fatty acids (C2 (acetic acid), C3 (propanoic acid), C4 (butyric acid) and C5 (pentanoic acid)) activate FFA2 [9, 62, 86] and FFA3 [9, 62] receptors. The crystal structure for agonist bound FFA1 has been described [108].
Kisspeptin receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Davenport Anthony P. , Maguire Janet J. , Mead Edward J.
Published: September 2019

The kisspeptin receptor (nomenclature as agreed by the NC-IUPHAR Subcommittee on the kisspeptin receptor [9]), like neuropeptide FF (NPFF), prolactin-releasing peptide (PrP) and QRFP receptors (provisional nomenclature) responds to endogenous peptides with an arginine-phenylalanine-amide (RFamide) motif. kisspeptin-54 (KP54, originally named metastin), kisspeptin-13 (KP13) and kisspeptin-10 (KP10) are biologically-active peptides cleaved from the KISS1 (Q15726) gene product. Kisspeptins have roles in, for example, cancer metastasis, fertility/puberty regulation and glucose homeostasis.
Neuromedin U receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Al-hosaini Khaled , Bloom Stephen R. , Hedrick Joseph , Howard Andrew , Jethwa Preeti , Luckman Simon , Raddatz Rita , Semjonous Nina , Willars Gary B.
Published: September 2019

Neuromedin U receptors (provisional nomenclature as recommended by NC-IUPHAR [29]) are activated by the endogenous 25 amino acid peptide neuromedin U (neuromedin U-25, NmU-25), a peptide originally isolated from pig spinal cord [90]. In humans, NmU-25 appears to be the sole product of a precursor gene (NMU, P48645) showing a broad tissue distribution, but which is expressed at highest levels in the upper gastrointestinal tract, CNS, bone marrow and fetal liver. Much shorter versions of NmU are found in some species, but not in human, and are derived at least in some instances from the proteolytic cleavage of the longer NmU. Despite species differences in NmU structure, the C-terminal region (particularly the C-terminal pentapeptide) is highly conserved and contains biological activity. Neuromedin S (neuromedin S-33) has also been identified as an endogenous agonist [95]. NmS-33 is, as its name suggests, a 33 amino-acid product of a precursor protein derived from a single gene and contains an amidated C-terminal heptapeptide identical to NmU. NmS-33 appears to activate NMU receptors with equivalent potency to NmU-25.
Neuropeptide S receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Caló Girolamo , Civelli Olivier , Reinscheid Rainer K. , Ruzza Chiara
Published: September 2019

The neuropeptide S receptor (NPS, provisional nomenclature [18]) responds to the 20 amino-acid peptide neuropeptide S derived from a precursor (NPS, P0C0P6).
Succinate receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Davenport Anthony P. , Hanson Julien , Liew Wen Chiy
Published: September 2019

Nomenclature as recommended by NC-IUPHAR [7]. The Succinate receptor has been identified as being activated by physiological levels of the Kreb's cycle intermediate succinate and other dicarboxylic acids such as maleate in 2004. Since its pairing with its endogenous ligand, the receptor has been the focus of intensive research and its role has been evidenced in various (patho)physiological processes such as regulation of renin production, retinal angiogenesis, inflammation or immune response.
Hydroxycarboxylic acid receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Colletti Steven L. , IJzerman Adriaan P. , Lovenberg Timothy W. , Offermanns Stefan , Semple Graeme , Waters M. Gerard , Wise Alan
Published: September 2019

The hydroxycarboxylic acid family of receptors (ENSFM00500000271913, nomenclature as agreed by the NC-IUPHAR Subcommittee on Hydroxycarboxylic acid receptors [32, 10]) respond to organic acids, including the endogenous hydroxy carboxylic acids 3-hydroxy butyric acid and L-lactic acid, as well as the lipid lowering agents nicotinic acid (niacin), acipimox and acifran [47, 54, 57]. These receptors were provisionally described as nicotinic acid receptors, although nicotinic acid shows submicromolar potency at HCA2 receptors only and is unlikely to be the natural ligand [54, 57].
Tachykinin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Barrett Jeffrey , Canning Brenden , Coulson Joseph , Dombrowsky Erin , Douglas Steven D. , Fong Tung M. , Heyward Christa Y. , Leeman Susan E. , Remeshwar Pranela
Published: September 2019

Tachykinin receptors (provisional nomenclature as recommended by NC-IUPHAR [90]) are activated by the endogenous peptides substance P (SP), neurokinin A (NKA; previously known as substance K, neurokinin α, neuromedin L), neurokinin B (NKB; previously known as neurokinin β, neuromedin K), neuropeptide K and neuropeptide γ (N-terminally extended forms of neurokinin A). The neurokinins (A and B) are mammalian members of the tachykinin family, which includes peptides of mammalian and nonmammalian origin containing the consensus sequence: Phe-x-Gly-Leu-Met. Marked species differences in in vitro pharmacology exist for all three receptors, in the context of nonpeptide ligands. Antagonists such as aprepitant and fosaprepitant were approved by FDA and EMA, in combination with other antiemetic agents, for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy.
5-HT3 receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Barnes Nicholas M. , Hales Tim G. , Lummis Sarah C. R. , Niesler Beate , Peters John A.
Published: September 2019

The 5-HT3 receptor (nomenclature as agreed by the NC-IUPHAR Subcommittee on 5-Hydroxytryptamine (serotonin) receptors [66]) is a ligand-gated ion channel of the Cys-loop family that includes the zinc-activated channels, nicotinic acetylcholine, GABAA and strychnine-sensitive glycine receptors. The receptor exists as a pentamer of 4TM subunits that form an intrinsic cation selective channel [5]. Five human 5-HT3 receptor subunits have been cloned and homo-oligomeric assemblies of 5-HT3A and hetero-oligomeric assemblies of 5-HT3A and 5-HT3B subunits have been characterised in detail. The 5-HT3C (HTR3C, Q8WXA8), 5-HT3D (HTR3D, Q70Z44) and 5-HT3E (HTR3E, A5X5Y0) subunits [83, 122], like the 5-HT3B subunit, do not form functional homomers, but are reported to assemble with the 5-HT3A subunit to influence its functional expression rather than pharmacological profile [124, 63, 157]. 5-HT3A, -C, -D, and -E subunits also interact with the chaperone RIC-3 which predominantly enhances the surface expression of homomeric 5-HT3A receptor [157]. The co-expression of 5-HT3A and 5-HT3C-E subunits has been demonstrated in human colon [82]. A recombinant hetero-oligomeric 5-HT3AB receptor has been reported to contain two copies of the 5-HT3A subunit and three copies of the 5-HT3B subunit in the order B-B-A-B-A [7], but this is inconsistent with recent reports which show at least one A-A interface [96, 150]. The 5-HT3B subunit imparts distinctive biophysical properties upon hetero-oligomeric 5-HT3AB versus homo-oligomeric 5-HT3A recombinant receptors [32, 41, 56, 85, 139, 129, 79], influences the potency of channel blockers, but generally has only a modest effect upon the apparent affinity of agonists, or the affinity of antagonists ([17], but see [41, 30, 35]) which may be explained by the orthosteric binding site residing at an interface formed between 5-HT3A subunits [96, 150]. However, 5-HT3A and 5-HT3AB receptors differ in their allosteric regulation by some general anaesthetic agents, small alcohols and indoles [138, 135, 71]. The potential diversity of 5-HT3 receptors is increased by alternative splicing of the genes HTR3A and E [64, 19, 124, 123, 120]. In addition, the use of tissue-specific promoters driving expression from different transcriptional start sites has been reported for the HTR3A, HTR3B, HTR3D and HTR3E genes, which could result in 5-HT3 subunits harbouring different N-termini [152, 79, 120]. To date, inclusion of the 5-HT3A subunit appears imperative for 5-HT3 receptor function.
CatSper and Two-Pore channels (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Chung Jean-Ju , Clapham David E. , Garbers David L. , Ren Dejian
Published: September 2019

CatSper channels (CatSper1-4, nomenclature as agreed by NC-IUPHAR [13]) are putative 6TM, voltage-gated, alkalinization-activated calcium permeant channels that are presumed to assemble as a tetramer of α-like subunits and mediate the current ICatSper [21]. In mammals, CatSper subunits are structurally most closely related to individual domains of voltage-activated calcium channels (Cav) [36]. CatSper1 [36], CatSper2 [33] and CatSpers 3 and 4 [25, 19, 32], in common with a putative 2TM auxiliary CatSperβ protein [24] and two putative 1TM associated CatSperγ and CatSperδ proteins [42, 11], are restricted to the testis and localised to the principle piece of sperm tail. The novel cross-species CatSper channel inhibitor, RU1968, has been proposed as a useful tool to aid characterisation of native CatSper channels [37].Two-pore channels (TPCs) are structurally related to CatSpers, CaVs and NaVs. TPCs have a 2x6TM structure with twice the number of TMs of CatSpers and half that of CaVs. There are three animal TPCs (TPC1-TPC3). Humans have TPC1 and TPC2, but not TPC3. TPC1 and TPC2 are localized in endosomes and lysosomes [4]. TPC3 is also found on the plasma membrane and forms a voltage-activated, non-inactivating Na+ channel [5]. All the three TPCs are Na+-selective under whole-cell or whole-organelle patch clamp recording [44, 7, 6]. The channels may also conduct Ca2+ [29].
Glycine receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Lynch Joseph. W. , Sivilotti Lucia G. , Smart Trevor G.
Published: September 2019

The inhibitory glycine receptor (nomenclature as agreed by the NC-IUPHAR Subcommittee on Glycine Receptors) is a member of the Cys-loop superfamily of transmitter-gated ion channels that includes the zinc activated channels, GABAA, nicotinic acetylcholine and 5-HT3 receptors [63]. The receptor is expressed either as a homo-pentamer of α subunits, or a complex now thought to harbour 2α and 3β subunits [30, 7], that contain an intrinsic anion channel. Four differentially expressed isoforms of the α-subunit (α1-α4) and one variant of the β-subunit (β1, GLRB, P48167) have been identified by genomic and cDNA cloning. Further diversity originates from alternative splicing of the primary gene transcripts for α1 (α1INS and α1del), α2 (α2A and α2B), α3 (α3S and α3L) and β (βΔ7) subunits and by mRNA editing of the α2 and α3 subunit [80, 91, 18]. Both α2 splicing and α3 mRNA editing can produce subunits (i.e., α2B and α3P185L) with enhanced agonist sensitivity. Predominantly, the mature form of the receptor contains α1 (or α3) and β subunits while the immature form is mostly composed of only α2 subunits. RNA transcripts encoding the α4-subunit have not been detected in adult humans. The N-terminal domain of the α-subunit contains both the agonist and strychnine binding sites that consist of several discontinuous regions of amino acids. Inclusion of the β-subunit in the pentameric glycine receptor contributes to agonist binding, reduces single channel conductance and alters pharmacology. The β-subunit also anchors the receptor, via an amphipathic sequence within the large intracellular loop region, to gephyrin. The latter is a cytoskeletal attachment protein that binds to a number of subsynaptic proteins involved in cytoskeletal structure and thus clusters and anchors hetero-oligomeric receptors to the synapse [86, 51, 53]. G-protein βγ subunits enhance the open state probability of native and recombinant glycine receptors by association with domains within the large intracellular loop [122, 121]. Intracellular chloride concentration modulates the kinetics of native and recombinant glycine receptors [94]. Intracellular Ca2+ appears to increase native and recombinant glycine receptor affinity, prolonging channel open events, by a mechanism that does not involve phosphorylation [24].
Inwardly rectifying potassium channels (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Adelman John P. , Clapham David E. , Hibino Hiroshi , Inanobe Atsushi , Jan Lily Y. , Karschin Andreas , Kubo Yoshihiro , Kurachi Yoshihisa , Lazdunski Michel , Miki Takashi , Nichols Colin G. , Palmer Lawrence G. , Pearson Wade L. , Sackin Henry , Seino Susumu , Slesinger Paul A. , Tucker Stephen , Vandenberg Carol A.
Published: September 2019

The 2TM domain family of K channels are also known as the inward-rectifier K channel family. This family includes the strong inward-rectifier K channels (Kir2.x) that are constitutively active, the G-protein-activated inward-rectifier K channels (Kir3.x) and the ATP-sensitive K channels (Kir6.x, which combine with sulphonylurea receptors (SUR1-3)). The pore-forming α subunits form tetramers, and heteromeric channels may be formed within subfamilies (e.g. Kir3.2 with Kir3.3).
Ceramide turnover (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Futerman Anthony H.
Published: September 2019

Ceramides are a family of sphingophospholipids synthesized in the endoplasmic reticulum, which mediate cell stress responses, including apoptosis, autophagy and senescence, Serine palmitoyltransferase generates 3-ketosphinganine, which is reduced to sphinganine (dihydrosphingosine). N-Acylation allows the formation of dihydroceramides, which are subsequently reduced to form ceramides. Once synthesized, ceramides are trafficked from the ER to the Golgi bound to the ceramide transfer protein, CERT (COL4A3BP, Q9Y5P4). Ceramide can be metabolized via multiple routes, ensuring tight regulation of its cellular levels. Addition of phosphocholine generates sphingomyelin while carbohydrate is added to form glucosyl- or galactosylceramides. Ceramidase re-forms sphingosine or sphinganine from ceramide or dihydroceramide. Phosphorylation of ceramide generates ceramide phosphate. The determination of accurate kinetic parameters for many of the enzymes in the sphingolipid metabolic pathway is complicated by the lipophilic nature of the substrates.
P2X receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Di Virgilio Francesco , Evans Richard J. , Falzoni Simonetta , Jarvis Michael F. , Kennedy Charles , Khakh Baljit S. , King Brian , Pellegatti Patrizia , Peters John A.
Published: September 2019

P2X receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on P2X Receptors [46, 134]) have a trimeric topology [118, 132, 177] with two putative TM domains, gating primarily Na+, K+ and Ca2+, exceptionally Cl-. The Nomenclature Subcommittee has recommended that for P2X receptors, structural criteria should be the initial criteria for nomenclature where possible. X-ray crystallography indicates that functional P2X receptors are trimeric and three agonist molecules are required to bind to a single receptor in order to activate it [132, 88, 96, 161]. Native receptors may occur as either homotrimers (e.g. P2X1 in smooth muscle) or heterotrimers (e.g. P2X2:P2X3 in the nodose ganglion [251], P2X1:P2X5 in mouse cortical astrocytes [146], and P2X2:P2X5 in mouse dorsal root ganglion, spinal cord and mid pons [50, 207]. P2X2, P2X4 and P2X7 receptors have been shown to form functional homopolymers which, in turn, activate pores permeable to low molecular weight solutes [229]. The hemi-channel pannexin-1 has been implicated in the pore formation induced by P2X7 [188], but not P2X2 [38], receptor activation.
Two P domain potassium channels (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Bayliss Douglas A. , Czirják Gábor , Enyedi Péter , Goldstein Steve A.N. , Lesage Florian , Minor, Jr. Daniel L. , Plant Leigh D. , Sepúlveda Francisco , Winn Brenda T.
Published: September 2019

The 4TM family of K channels mediate many of the background potassium currents observed in native cells. They are open across the physiological voltage-range and are regulated by a wide array of neurotransmitters and biochemical mediators. The pore-forming α-subunit contains two pore loop (P) domains and two subunits assemble to form one ion conduction pathway lined by four P domains. It is important to note that single channels do not have two pores but that each subunit has two P domains in its primary sequence; hence the name two P domain, or K2P channels (and not two-pore channels). Some of the K2P subunits can form heterodimers across subfamilies (e.g. K2P3.1 with K2P9.1). The nomenclature of 4TM K channels in the literature is still a mixture of IUPHAR and common names. The suggested division into subfamilies, described in the More detailed introduction, is based on similarities in both structural and functional properties within subfamilies and this explains the "common abbreviation" nomenclature in the tables below.
Hydrolases (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Alexander Stephen P.H. , Doherty Patrick , Fairlie David , Fowler Christopher J. , Overall Christopher M. , Rawlings Neil , Southan Christopher , Turner Anthony J.
Published: September 2019

Listed in this section are hydrolases not accumulated in other parts of the Concise Guide, such as monoacylglycerol lipase and acetylcholinesterase. Pancreatic lipase is the predominant mechanism of fat digestion in the alimentary system; its inhibition is associated with decreased fat absorption. CES1 is present at lower levels in the gut than CES2 (P23141), but predominates in the liver, where it is responsible for the hydrolysis of many aliphatic, aromatic and steroid esters. Hormone-sensitive lipase is also a relatively non-selective esterase associated with steroid ester hydrolysis and triglyceride metabolism, particularly in adipose tissue. Endothelial lipase is secreted from endothelial cells and regulates circulating cholesterol in high density lipoproteins.
Voltage-gated calcium channels (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Catterall William A. , Perez-Reyes Edward , Snutch Terrance P. , Striessnig Jörg
Published: September 2019

Calcium (Ca2+) channels are voltage-gated ion channels present in the membrane of most excitable cells. The nomenclature for Ca2+channels was proposed by [110] and approved by the NC-IUPHAR Subcommittee on Ca2+ channels [60]. Ca2+ channels form hetero-oligomeric complexes. The α1 subunit is pore-forming and provides the binding site(s) for practically all agonists and antagonists. The 10 cloned α1-subunits can be grouped into three families: (1) the high-voltage activated dihydropyridine-sensitive (L-type, CaV1.x) channels; (2) the high-voltage activated dihydropyridine-insensitive (CaV2.x) channels and (3) the low-voltage-activated (T-type, CaV3.x) channels. Each α1 subunit has four homologous repeats (I–IV), each repeat having six transmembrane domains and a pore-forming region between transmembrane domains S5 and S6. Gating is thought to be associated with the membrane-spanning S4 segment, which contains highly conserved positive charges. Many of the α1-subunit genes give rise to alternatively spliced products. At least for high-voltage activated channels, it is likely that native channels comprise co-assemblies of α1, β and α2–δ subunits. The γ subunits have not been proven to associate with channels other than the α1s skeletal muscle Cav1.1 channel. The α2–δ1 and α2–δ2 subunits bind gabapentin and pregabalin.