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Differentiation of bovine from porcine gelatin capsules using gel electrophoresis method

Yap BK, Gam LH

Food Chem, 2019 Feb 15;274:16-19.
PMID: 30372921 DOI: 10.1016/j.foodchem.2018.08.111

Gelatin is commonly used in food supplements and in the form of soft or hard capsules. The source of gelatins is usually from porcine and bovine, and less commonly from vegetable and fish. Nevertheless, these different origins of gelatin have much similarity in term of structures, physicochemical properties and amino acid sequences. Due to these reasons, differentiation of the source of gelatins has been very difficult. In our present study, differentiation of sources of gelatin was made possible in a simplified yet economical method. Sample was prepared using ammonium sulfate precipitation and subjected to gel electrophoresis for protein separation. We have found a fraction of proteins which is able to differentiate porcine and bovine gelatins accurately, with distinctive protein bands in SDS-PAGE at 140 kDa and 110 kDa for bovine and porcine samples, respectively. This method was verified by 13 double-blinded gelatin samples, all the 13 samples were accurately identified.
In Silico Prediction and Biophysical Validation of Novel 14-3-3σ Homodimer Stabilizers

Aljabal G, Teh AH, Yap BK

J Chem Inf Model, 2023 Sep 11;63(17):5619-5630.
PMID: 37606921 DOI: 10.1021/acs.jcim.3c00791

14-3-3σ plays an important role in controlling tumor metabolic reprogramming and cancer cell growth. However, its function is often compromised in many cancers due to its downregulation. Previous studies found that homodimerization of 14-3-3σ is critical for its activity. However, to date, it is not known if stabilization of 14-3-3σ homodimers can improve its activity or prevent its degradation. In our previous work, we have showed that GCP-Lys-OMe is a potential 14-3-3σ homodimer stabilizer. However, its stabilizing effect was not experimentally validated. Therefore, in this study, we have attempted to predict few potential peptides that can stabilize the dimeric form of 14-3-3σ using similar in silico techniques as described previously for GCP-Lys-OMe. Subsequent [1H]-CPMG NMR experiments confirmed the binding of the peptides (peptides 3, 5, 9, and 16) on 14-3-3σ, with peptide 3 showing the strongest binding. Competitive [1H]-CPMG assays further revealed that while peptide 3 does not compete with a 14-3-3σ binding peptide (ExoS) for the protein's amphipathic groove, it was found to improve ExoS binding on 14-3-3σ. When 14-3-3σ was subjected to dynamic light scattering experiments, the 14-3-3σ homodimer was found to undergo dissociation into monomers prior to aggregation. Intriguingly, the presence of peptide 3 increased 14-3-3σ stability against aggregation. Overall, our findings suggest that (1) docking accompanied by MD simulations can be used to identify potential homodimer stabilizing compounds of 14-3-3σ and (2) peptide 3 can slow down 14-3-3σ aggregation (presumably by preventing its dissociation into monomers), as well as improving the binding of 14-3-3σ to ExoS protein.
Identification of peptide binding sequence of TRIM25 on 14-3-3σ by bioinformatics and biophysical techniques

Chiang C, Teh AH, Yap BK

J Biomol Struct Dyn, 2023;41(22):13260-13270.
PMID: 36724456 DOI: 10.1080/07391102.2023.2172458

14-3-3σ protein is one of the seven isoforms from the highly conserved eukaryotic 14-3-3 protein family. Downregulation of 14-3-3σ expression has been observed in various tumors. TRIM25 is responsible for the proteolytic degradation of 14-3-3σ, in which abrogation of TRIM25 suppressed tumor growth through 14-3-3σ upregulation. However, to date, the exact 14-3-3σ interacting residues of TRIM25 have yet to be resolved. Thus, this study attempts to identify the peptide binding sequence of TRIM25 on 14-3-3σ via both bioinformatics and biophysical techniques. Multiple sequence alignment of the CC domain of TRIM25 revealed five potential peptide binding sequences (Peptide 1-5). Nuclear magnetic resonance (NMR) assay (1H CPMG) identified Peptide 1 as an important sequence for binding to 14-3-3σ. Competition NMR assay suggested that Peptide 1 binds to the amphipathic pocket of 14-3-3σ with an estimated KD of 116.4 µM by isothermal titration calorimetry. Further in silico docking and molecular dynamics simulations studies proposed that Peptide 1 is likely to interact with Lys49, Arg56, Arg129, and Tyr130 residues at the amphipathic pocket of 14-3-3σ. These results suggest that Peptide 1 may serve as a biological probe or a template to design inhibitors of TRIM25-14-3-3σ interaction as a potentially novel class of anticancer agents.Communicated by Ramaswamy H. Sarma.
Homology modeling of the human 5-HT1A, 5-HT 2A, D1, and D2 receptors: model refinement with molecular dynamics simulations and docking evaluation

Yap BK, Buckle MJ, Doughty SW

J Mol Model, 2012 Aug;18(8):3639-55.
PMID: 22354276 DOI: 10.1007/s00894-012-1368-5

5-HT(1A) serotonin and D1 dopamine receptor agonists have been postulated to be able to improve negative and cognitive impairment symptoms of schizophrenia, while partial agonists and antagonists of the D2 and 5-HT(2A) receptors have been reported to be effective in reducing positive symptoms. There is therefore a need for well-defined homology models for the design of more selective antipsychotic agents, since no three-dimensional (3D) crystal structures of these receptors are currently available. In this study, homology models were built based on the high-resolution crystal structure of the β(2)-adrenergic receptor (2RH1) and further refined via molecular dynamics simulations in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer system with the GROMOS96 53A6 united atom force field. Docking evaluations with representative agonists and antagonists using AutoDock 4.2 revealed binding modes in agreement with experimentally determined site-directed mutagenesis data and significant correlations between the computed and experimental pK (i) values. The models are also able to distinguish between antipsychotic agents with different selectivities and binding affinities for the four receptors, as well as to differentiate active compounds from decoys. Hence, these human 5-HT(1A), 5-HT(2A), D1 and D2 receptor homology models are capable of predicting the activities of novel ligands, and can be used as 3D templates for antipsychotic drug design and discovery.
Polymer-enhanced perovskite oxide-based photocatalysts: a review

Thien GSH, Chan KY, Marlinda AR, Yap BK

Nanoscale, 2023 Dec 07;15(47):19039-19061.
PMID: 37987540 DOI: 10.1039/d3nr03874b

Oxide perovskites (OPs) have emerged as promising photocatalysts for numerous applications, such as energy conversion, renewable fuels, and environmental remediation. Although OPs are gaining traction, their efficacies are still hindered by low charge carrier mobility and poor stability. This study investigated the function of polymers actively participating in OP structures to improve the overall characteristics. An overview of the polymer-enhanced perovskite oxide photocatalyst (PEPOP) field was effectively reviewed. These PEPOPs were demonstrated in photovoltaics, pollutant degradation, and gas conversion and reduction. Nonetheless, additional research is needed to explore the potential of PEPOPs to establish their efficacy in photocatalytic applications. The technological improvements of PEPOPs were hindered by significant challenges related to stability and sensitivity. The urgency of this review was apparent due to the fast-paced nature of research in the field of photocatalysis. Recent breakthroughs and emerging applications highlight the need for a comprehensive overview of PEPOPs and their enhanced catalytic capabilities. Consequently, a broad outlook was provided for the current state of PEPOP-related studies, highlighting the potential of these materials for future applications.
Structure-based identification of aporphines with selective 5-HT(2A) receptor-binding activity

Munusamy V, Yap BK, Buckle MJ, Doughty SW, Chung LY

Chem Biol Drug Des, 2013 Feb;81(2):250-6.
PMID: 23039820 DOI: 10.1111/cbdd.12069

Selective blockade of the serotonin 5-HT(2A) receptor is a useful therapeutic approach for a number of disorders, including schizophrenia, insomnia and ischaemic heart disease. A series of aporphines were docked into a homology model of the rat 5-HT(2A) receptor using AutoDock. Selected compounds with high in silico binding affinities were screened in vitro using radioligand-binding assays against rat serotonin (5-HT(1A) and 5-HT(2A)) and dopamine (D1 and D2) receptors. (R)-Roemerine and (±)-nuciferine were found to have high affinity for the 5-HT(2A) receptor (K(i) = 62 and 139 nM, respectively), with (R)-roemerine showing 20- to 400-fold selectivity for the 5-HT(2A) receptor over the 5-HT(1A), D1 and D2 receptors. Investigation into the ligand-receptor interactions suggested that the selectivity of (R)-roemerine is due to it having stronger H-bonding and dipole-dipole interactions with several of the key residues in the 5-HT(2A) receptor-binding site.
Roles of Ki67 in Breast Cancer - Important for Management?

Yip Ch, Bhoo-Pathy N, Daniel J, Foo Y, Mohamed A, Abdullah M, et al.

Asian Pac J Cancer Prev, 2016;17(3):1077-82.
PMID: 27039727

BACKGROUND: The three standard biomarkers used in breast cancer are the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The Ki-67 index, a proliferative marker, has been shown to be associated with a poorer outcome, and despite absence of standardization of pathological assessment, is widely used for therapy decision making. We aim to study the role of the Ki-67 index in a group of Asian women with breast cancer.
MATERIALS AND METHODS: A total of 450 women newly diagnosed with Stage 1 to 3 invasive breast cancer in a single centre from July 2013 to Dec 2014 were included in this study. Univariable and multivariable logistic regression was used to determine the association between Ki-67 (positive defined as 14% and above) and age, ethnicity, grade, mitotic index, ER, PR, HER2, lymph node status and size. All analyses were performed using SPSS Version 22.
RESULTS: In univariable analysis, Ki -67 index was associated with younger age, higher grade, ER and PR negativity, HER2 positivity, high mitotic index and positive lymph nodes. However on multivariable analysis only tumour size, grade, PR and HER2 remained significant. Out of 102 stage 1 patients who had ER positive/PR positive/HER2 negative tumours and non-grade 3, only 5 (4.9%) had a positive Ki-67 index and may have been offered chemotherapy. However, it is interesting to note that none of these patients received chemotherapy.
CONCLUSIONS: Information on Ki67 would have potentially changed management in an insignificant proportion of patients with stage 1 breast cancer.
Fulltext Heterocyclic Substitutions Greatly Improve Affinity and Stability of Folic Acid towards FRα. an In Silico Insight

Al-Thiabat MG, Saqallah FG, Gazzali AM, Mohtar N, Yap BK, Choong YS, et al.

Molecules, 2021 Feb 18;26(4).
PMID: 33670773 DOI: 10.3390/molecules26041079

Folate receptor alpha (FRα) is known as a biological marker for many cancers due to its overexpression in cancerous epithelial tissue. The folic acid (FA) binding affinity to the FRα active site provides a basis for designing more specific targets for FRα. Heterocyclic rings have been shown to interact with many receptors and are important to the metabolism and biological processes within the body. Nineteen FA analogs with substitution with various heterocyclic rings were designed to have higher affinity toward FRα. Molecular docking was used to study the binding affinity of designed analogs compared to FA, methotrexate (MTX), and pemetrexed (PTX). Out of 19 FA analogs, analogs with a tetrazole ring (FOL03) and benzothiophene ring (FOL08) showed the most negative binding energy and were able to interact with ASP81 and SER174 through hydrogen bonds and hydrophobic interactions with amino acids of the active site. Hence, 100 ns molecular dynamics (MD) simulations were carried out for FOL03, FOL08 compared to FA, MTX, and PTX. The root mean square deviation (RMSD) and root mean square fluctuation (RMSF) of FOL03 and FOL08 showed an apparent convergence similar to that of FA, and both of them entered the binding pocket (active site) from the pteridine part, while the glutamic part was stuck at the FRα pocket entrance during the MD simulations. Molecular mechanics Poisson-Boltzmann surface accessible (MM-PBSA) and H-bond analysis revealed that FOL03 and FOL08 created more negative free binding and electrostatic energy compared to FA and PTX, and both formed stronger H-bond interactions with ASP81 than FA with excellent H-bond profiles that led them to become bound tightly in the pocket. In addition, pocket volume calculations showed that the volumes of active site for FOL03 and FOL08 inside the FRα pocket were smaller than the FA-FRα system, indicating strong interactions between the protein active site residues with these new FA analogs compared to FA during the MD simulations.
Fulltext Effects of UV Irradiation and Storage on the Performance of Inverted Red Quantum-Dot Light-Emitting Diodes

Luo Y, Wang J, Wang P, Mai C, Wang J, Yap BK, et al.

Nanomaterials (Basel), 2021 Jun 18;11(6).
PMID: 34207371 DOI: 10.3390/nano11061606

We report the effects of ultraviolet (UV) irradiation and storage on the performance of ZnO-based inverted quantum-dot light-emitting diodes (QLEDs). The effects of UV irradiation on the electrical properties of ZnO nanoparticles (NPs) were investigated. We demonstrate that the charge balance was enhanced by improving the electron injection. The maximum external quantum efficiency (EQE) and power efficiency (PE) of QLEDs were increased by 26% and 143% after UV irradiation for 15 min. In addition, we investigated the storage stabilities of the inverted QLEDs. During the storage period, the electron current from ZnO gradually decreased, causing a reduction in the device current. However, the QLEDs demonstrated improvements in maximum EQE by 20.7% after two days of storage. Our analysis indicates that the suppression of exciton quenching at the interface of ZnO and quantum dots (QDs) during the storage period could result in the enhancement of EQE. This study provides a comprehension of the generally neglected factors, which could be conducive to the realization of high-efficiency and highly storage-stable practical applications.
Fulltext Potential Point-of-Care Microfluidic Devices to Diagnose Iron Deficiency Anemia

Yap BK, M Soair SN, Talik NA, Lim WF, Mei I L

Sensors (Basel), 2018 Aug 10;18(8).
PMID: 30103424 DOI: 10.3390/s18082625

Over the past 20 years, rapid technological advancement in the field of microfluidics has produced a wide array of microfluidic point-of-care (POC) diagnostic devices for the healthcare industry. However, potential microfluidic applications in the field of nutrition, specifically to diagnose iron deficiency anemia (IDA) detection, remain scarce. Iron deficiency anemia is the most common form of anemia, which affects billions of people globally, especially the elderly, women, and children. This review comprehensively analyzes the current diagnosis technologies that address anemia-related IDA-POC microfluidic devices in the future. This review briefly highlights various microfluidics devices that have the potential to detect IDA and discusses some commercially available devices for blood plasma separation mechanisms. Reagent deposition and integration into microfluidic devices are also explored. Finally, we discuss the challenges of insights into potential portable microfluidic systems, especially for remote IDA detection.
Fulltext Retrospective Analysis of Cancer Care Performance and Survival Outcome for Nasopharyngeal Carcinoma at a leading Cancer Treatment Centre in Malaysia 2008-2012

Abdullah MM, Foo YC, Yap BK, Lee CML, Hoo LP, Lim TO

Asian Pac J Cancer Prev, 2019 06 01;20(6):1701-1708.
PMID: 31244290 DOI: 10.31557/APJCP.2019.20.6.1701

Objective: This report focuses on a private medical centre cancer care performance as measured by patient survival
outcome for up to 5 years. Methods: All patients with nasopharyngeal cancer treated at SJMC between 2008 and 2012
were enrolled for this observational cohort study. Mortality outcome was ascertained through record linkage with
national death register, linkage with hospital registration system and finally through direct contact by phone. Result:
266 patients treated between 2008 and 2012 were included for survival analysis. 31% of patients were diagnosed with
Early NPC Cancer (Stage I or II), another 44% with Locally Advanced Cancer (Stage III) and 25% with late stage IV
metastatic cancer. 2%, 27% and 67% had WHO Class I, II and III NPC respectively. The overall survival at 5 years
was 100% for patients with Stage I disease, 91% for Stage II disease, 72% for Stage III disease, and decreasing to
44% for Stage IV disease. Overall survival at 5 years for all stages was 73%. Conclusion: SJMC is among the first
hospitals in Malaysia to embark on routine measurement of the performance of its cancer care services and its results
are comparable to any leading centers in developed countries.
Accelerating charge transfer via nonconjugated polyelectrolyte interlayers toward efficient versatile photoredox catalysis

Li T, Feng C, Yap BK, Zhu X, Xiong B, He Z, et al.

Commun Chem, 2021 Oct 22;4(1):150.
PMID: 36697810 DOI: 10.1038/s42004-021-00589-w

One of the challenges for high-efficiency single-component-based photoredox catalysts is the low charge transfer and extraction due to the high recombination rate. Here, we demonstrate a strategy to precisely control the charge separation and transport efficiency of the catalytic host by introducing electron or hole extraction interlayers to improve the catalytic efficiency. We use simple and easily available non-conjugated polyelectrolytes (NCPs) (i.e., polyethyleneimine, PEI; poly(allylamine hydrochloride), PAH) to form interlayers, wherein such NCPs consist of the nonconjugated backbone with charge transporting functional groups. Taking CdS as examples, it is shown that although PEI and PAH are insulators and therefore do not have the ability to conduct electricity, they can form good electron or hole transport extraction layers due to the higher charge-transfer kinetics of pendant groups along the backbones, thereby greatly improving the charge transfer capability of CdS. Consequently, the resultant PEI-/PAH-functionalized nanocomposites exhibit significantly enhanced and versatile photoredox catalysis.
Rapid Nucleation of Reduced Graphene Oxide-Supported Palladium Electrocatalysts for Methanol Oxidation Reaction

Ng JC, Tan CY, Ong BH, Matsuda A, Basirun WJ, Tan WK, et al.

J Nanosci Nanotechnol, 2019 Nov 01;19(11):7236-7243.
PMID: 31039881 DOI: 10.1166/jnn.2019.16717

Small sized electrocatalysts, which can be obtained by rapid nucleation and high supersaturation are imperative for outstanding methanol oxidation reaction (MOR). Conventional microwave synthesis processes of electrocatalysts include ultrasonication, stirring, pH adjustment, and microwave irradiation of the precursor mixture. Ethylene glycol (EG), which serves as a reductant and solvent was added during the ultrasonication or stirring stage. However, this step and pH adjustment resulted in unintended multi-stage gradual nucleation. In this study, the microwave reduction approach was used to induce rapid nucleation and high supersaturation in order to fabricate small-sized reduced graphene oxide-supported palladium (Pd/rGO) electrocatalysts via the delayed addition of EG, elimination of the pH adjustment step, addition of sodium carbonate (Na₂CO₃), prior microwave irradiation of the EG mixed with Na₂CO₃, and addition of room temperature precursor mixture. Besides its role as a second reducing agent, the addition of Na₂CO₃ was primarily intended to generate an alkaline condition, which is essential for the high-performance of electrocatalysts. Moreover, the microwave irradiation of the EG and Na₂CO₃ mixture generated highly reactive free radicals that facilitate rapid nucleation. Meanwhile, the room temperature precursor mixture increased supersaturation. Results showed improved electrochemically active surface area (78.97 m² g-1, 23.79% larger), MOR (434.49 mA mg-1, 37.96% higher) and stability.
A Green Approach to Natural Dyes in Dye-Sensitized Solar Cells

Shukor NIA, Chan KY, Thien GSH, Yeoh ME, Low PL, Devaraj NK, et al.

Sensors (Basel), 2023 Oct 12;23(20).
PMID: 37896506 DOI: 10.3390/s23208412

Solar cells are pivotal in harnessing renewable energy for a greener and more sustainable energy landscape. Nonetheless, eco-friendly materials for solar cells have not been as extensive as conventional counterparts, highlighting a significant area for further investigation in advancing sustainable energy technologies. This study investigated natural dyes from cost-effective and environmentally friendly blueberries and mulberries. These dyes were utilized as alternative sensitizers for dye-sensitized solar cells (DSSCs). Alongside the natural dyes, a green approach was adopted for the DSSC design, encompassing TiO2 photoanodes, eco-friendly electrolytes, and green counter-electrodes created from graphite pencils and candle soot. Consequently, the best-optimized dye sensitizer was mulberry, with an output power of 13.79 µW and 0.122 µW for outdoor and indoor environments, respectively. This study underscored the feasibility of integrating DSSCs with sensitizers derived from readily available food ingredients, potentially expanding their applications in educational kits and technology development initiatives.
Fulltext Conjugated β-Cyclodextrin Enhances the Affinity of Folic Acid towards FRα: Molecular Dynamics Study

Al-Thiabat MG, Gazzali AM, Mohtar N, Murugaiyah V, Kamarulzaman EE, Yap BK, et al.

Molecules, 2021 Aug 31;26(17).
PMID: 34500740 DOI: 10.3390/molecules26175304

Drug targeting is a progressive area of research with folate receptor alpha (FRα) receiving significant attention as a biological marker in cancer drug delivery. The binding affinity of folic acid (FA) to the FRα active site provides a basis for recognition of FRα. In this study, FA was conjugated to beta-cyclodextrin (βCD) and subjected to in silico analysis (molecular docking and molecular dynamics (MD) simulation (100 ns)) to investigate the affinity and stability for the conjugated system compared to unconjugated and apo systems (ligand free). Docking studies revealed that the conjugated FA bound into the active site of FRα with a docking score (free binding energy < -15 kcal/mol), with a similar binding pose to that of unconjugated FA. Subsequent analyses from molecular dynamics (MD) simulations, root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg) demonstrated that FA and FA-βCDs created more dynamically stable systems with FRα than the apo-FRα system. All systems reached equilibrium with stable RMSD values ranging from 1.9-2.4 Å and the average residual fluctuation values of the FRα backbone atoms for all residues (except for terminal residues ARG8, THR9, THR214, and LEU215) were less than 2.1 Å with a consistent Rg value of around 16.8 Å throughout the MD simulation time (0-100 ns). The conjugation with βCD improved the stability and decreased the mobility of all the residues (except residues 149-151) compared to FA-FRα and apo-FRα systems. Further analysis of H-bonds, binding free energy (MM-PBSA), and per residue decomposition energy revealed that besides APS81, residues HIS20, TRP102, HIS135, TRP138, TRP140, and TRP171 were shown to have more favourable energy contributions in the holo systems than in the apo-FRα system, and these residues might have a direct role in increasing the stability of holo systems.
Fulltext Recent Advances in Halide Perovskite Resistive Switching Memory Devices: A Transformation from Lead-Based to Lead-Free Perovskites

Thien GSH, Ab Rahman M, Yap BK, Tan NML, He Z, Low PL, et al.

ACS Omega, 2022 Nov 08;7(44):39472-39481.
PMID: 36385870 DOI: 10.1021/acsomega.2c03206

Due to their remarkable electrical and light absorption characteristics, hybrid organic-inorganic perovskites have recently gained popularity in several applications such as optoelectronics, lasers, and light-emitting diodes. Through this, there has recently been an increase in the use of halide perovskites (HPs) in resistive switching (RS) devices. However, lead-based (Pb-based) perovskites are notorious for being unstable and harmful to the environment. As a result, lead-free (Pb-free) perovskite alternatives are being investigated in achieving the long-term and sustainable use of RS devices. This work describes the characteristics of Pb-based and Pb-free perovskite RS devices. It also presents the recent advancements of HP RS devices, including the selection strategies of perovskite structures. In terms of resistive qualities, the directions of both HPs appear to be identical. Following that, the possible impact of switching from Pb-based to Pb-free HPs is examined to determine the requirement in RS devices. Finally, this work discusses the opportunities and challenges of HP RS devices in creating a stable, efficient, and sustainable memory storage technology.
A Cyclic Peptide Inhibitor of the iNOS-SPSB Protein-Protein Interaction as a Potential Anti-Infective Agent

Sadek MM, Barlow N, Leung EWW, Williams-Noonan BJ, Yap BK, Shariff FM, et al.

ACS Chem. Biol., 2018 10 19;13(10):2930-2938.
PMID: 30226743 DOI: 10.1021/acschembio.8b00561

SPRY domain- and SOCS box-containing proteins SPSB1, SPSB2, and SPSB4 interact with inducible nitric oxide synthase (iNOS), causing the iNOS to be polyubiquitinated and targeted for degradation. Inhibition of this interaction increases iNOS levels, and consequently cellular nitric oxide (NO) concentrations, and has been proposed as a potential strategy for killing intracellular pathogens. We previously described two DINNN-containing cyclic peptides (CP1 and CP2) as potent inhibitors of the murine SPSB-iNOS interaction. In this study, we report the crystal structures of human SPSB4 bound to CP1 and CP2 and human SPSB2 bound to CP2. We then used these structures to design a new inhibitor in which an intramolecular hydrogen bond was replaced with a hydrocarbon linkage to form a smaller macrocycle while maintaining the bound geometry of CP2 observed in the crystal structures. This resulting pentapeptide SPSB-iNOS inhibitor (CP3) has a reduced macrocycle ring size, fewer nonbinding residues, and includes additional conformational constraints. CP3 has a greater affinity for SBSB2 ( KD = 7 nM as determined by surface plasmon resonance) and strongly inhibits the SPSB2-iNOS interaction in macrophage cell lysates. We have also determined the crystal structure of CP3 in complex with human SPSB2, which reveals the structural basis for the increased potency of CP3 and validates the original design.
Real-world multicenter study of the safety and efficacy of netupitant plus palonosetron fixed-dose combination to prevent chemotherapy-induced nausea and vomiting among Malaysian patients receiving moderately or highly emetogenic chemotherapy

Md Yusof M, Abdullah MM, Yap BK, Ng SC, Low JSH, Lam KS, et al.

Asia Pac J Clin Oncol, 2021 Nov 23.
PMID: 34811924 DOI: 10.1111/ajco.13667

AIM: A large proportion of cancer patients are at high risk for chemotherapy-induced nausea and vomiting (CINV), but the choice of anti-emetics for CINV in Malaysia is limited.
METHODS: This was a real-world study of a fixed-dose combination of netupitant and palonosetron (NEPA) to inhibit CINV in adult patients receiving moderately (MEC) or highly emetogenic chemotherapy (HEC) for solid/hematological malignancies at eight Malaysian centers. Each HEC/MEC cycle received one dose of NEPA + dexamethasone for CINV prevention. Complete response (no emesis, no rescue medication) (CR), no more than mild nausea (severity score ≤ 2.5), and complete control (CR) (no more than mild nausea) during the acute (0-24 h), delayed (25-120 h), and overall (0-120 h) phases post-chemotherapy were measured. Treatment-related adverse events (AEs) were recorded.
RESULTS: During March 2016-April 2018 (NMRR-17-3286-38282), NEPA + dexamethasone was administered to 54 patients (77.8% solid, 22.2% hematological malignancies). Note that 59.3% received HEC, while 40.7% received MEC regimen. During the overall phase of the first cycle, the majority had CR (77.8%), no more than mild nausea (74.1%), and complete control (61.1%). Seventeen patients received two consecutive cycles at any point of chemotherapy cycles. During the overall phases across two consecutive cycles, all patients achieved CR, and the majority reported no more than mild nausea and complete control. No grades 3-4 AEs were reported.
CONCLUSIONS: NEPA had sustained efficacy and tolerability at first administration and across two cycles of MEC/HEC for CINV prevention.

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