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sitagliptin phosphate + ipragliflozin L-proline (Sujanu / MK0431J)

✓ Approved

Kotobuki Pharmaceutical Co., Ltd. · DPP4 · Small Molecule

What is sitagliptin phosphate + ipragliflozin L-proline?

sitagliptin phosphate + ipragliflozin L-proline is a small molecule developed by Kotobuki Pharmaceutical Co., Ltd.. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesSujanu, MK0431J
CompanyKotobuki Pharmaceutical Co., Ltd.
Drug ClassSmall Molecule
Molecular TargetDPP4, SLC5A2
RouteOral (PO)
StatusApproved

Mechanism of Action

Molecular Targets

sitagliptin phosphate + ipragliflozin L-proline acts on 2 molecular targets:

DPP4dipeptidyl peptidase 4 (CD26, DPPIV)
SLC5A2solute carrier family 5 member 2 (SGLT2)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

sitagliptin phosphate + ipragliflozin L-proline is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Metabolism and nutrition disordersType 2 diabetes mellitus✓ Approved

Related Research Articles

PubMedNature genetics2026-10-15

Author Correction: Histone H3 proline 16 hydroxylation regulates mammalian gene expression.

Liu Xijuan X, Wang Jun J, Boyer Joshua A JA, Gong Weida W et al.

PubMedFrontiers in plant science2026-10-15

Physiological response strategies of pioneer endemic species Artemisia wudanica along an aeolian disturbance gradient in semi-arid active sand dunes.

Zhang Chi C, Wang Haitao H, Wang Yongcui Y, Qiu Yu Y et al.

Wind erosion and sand burial are recurrent but physically distinct aeolian disturbances in semi-arid dune systems. We investigated how Artemisia wudanica seedlings respond physiologically to matched relative gradients of simulated substrate removal and sand burial under controlled pot conditions. Seedlings were subjected to five simulated wind-erosion levels (0, 2, 4, 6, and 8 cm) and five sand-burial levels (0, 1.7, 3.3, 5.0, and 6.7 cm). Chlorophyll, proline, soluble sugar, malondialdehyde (MDA), peroxidase (POD), and superoxide dismutase (SOD) were quantified. Treatment effects were evaluated using two-way ANOVA, PCA of standardized variables, disturbance-specific Spearman correlations, and an exploratory path analysis. Disturbance type, relative disturbance level, and their interaction affected all six physiological traits, and PCA separated the two-treatment series in multivariate space. Under sand burial, chlorophyll, proline, and soluble sugar showed positive within-treatment covariation after Spearman correlations. Under simulated wind erosion, POD and SOD covaried positively, whereas MDA was not significantly correlated with either antioxidant enzyme; chlorophyll-proline and soluble sugar-MDA associations also remained significant after correction. The exploratory path model had limited overall fit and was used only to summarize statistical associations, not to establish causal physiological mechanisms. Under the controlled conditions of this seedling experiment, the two isolated treatments were associated with different physiological response and covariation patterns. These results provide testable hypotheses about disturbance-specific seedling responses rather than evidence of switchable association, population-level persistence, or restoration performance. Validation is required under field conditions, across additional life stages, and with pulsed and combined erosion-burial events.

PubMedFrontiers in cellular and infection microbiology2026-10-15

Integrative transcriptomic and lipidomic analysis of the effects of Eucommia ulmoides on growth performance and lipid metabolism in Larimichthys crocea.

Zhang Xuan X, Guo Xiangyu X, Hu Kun K, Ai Qinghui Q et al.

Larimichthys crocea is an economically important marine aquaculture species, and improving growth performance while maintaining lipid metabolic homeostasis is important for its sustainable production. This study investigated the effects of dietary Eucommia ulmoides supplementation on growth performance and lipid metabolism in L. crocea and explored the underlying molecular basis using integrated transcriptomic and lipidomic analyses. A 4-week feeding trial was conducted using a control diet and a diet supplemented with 0.3% E. ulmoides. Growth performance, plasma biochemical indices, hepatic lipid accumulation, transcriptomic profiles, and lipidomic profiles were evaluated. Integrated pathway analysis was further performed to identify metabolic pathways jointly represented in the transcriptomic and lipidomic datasets. Dietary supplementation with 0.3% E. ulmoides significantly increased the specific growth rate (SGR) of L. crocea (P < 0.05) and reduced the feed conversion ratio (FCR; 1.38 in the E. ulmoides group versus 2.68 in the control group). Hepatic Oil Red O staining revealed reduced lipid staining in the E. ulmoides group, while plasma biochemical analyses showed decreased triglyceride levels and improved antioxidant status. Integrated transcriptomic and lipidomic analyses identified glycerolipid metabolism and glycerophospholipid metabolism as the principal pathways represented in both omics datasets. In glycerolipid metabolism, differentially expressed genes (DEGs) were mapped to reactions involving intermediate metabolites associated with neutral-lipid synthesis. In glycerophospholipid metabolism, DEGs were mapped to reactions involving phosphatidylglycerol (PG), phosphatidylcholine (PC), phosphatidylethanolamine (PE), and their precursors. Notably, pathway-level co-mapping showed that these two metabolic pathways converge at phosphatidic acid (PA; 1,2-diacyl-sn-glycerol-3-phosphate), suggesting a potential metabolic connection between neutral-lipid storage and membrane lipid remodeling. These findings indicate that dietary E. ulmoides supplementation can improve growth performance and modulate lipid metabolism in L. crocea. The coordinated changes in glycerolipid and glycerophospholipid metabolism, potentially linked through PA, provide a molecular basis for the observed reduction in hepatic lipid accumulation and suggest that E. ulmoides may promote lipid metabolic homeostasis in L. crocea.

PubMedPakistan journal of biological sciences : PJBS2026-10-15

Salt Tolerance Variation among Chenopodium quinoa Accessions of Contrasting Geographic Origins: Germination Performance and Antioxidant Defense under NaCl Stress.

Arraouadi Soumaya S, Slimani Narmine N, Hajlaoui Hafedh H

<b>Background and Objective:</b> Chenopodium quinoa Willd. is a strategic crop for food security in salt-affected regions; however, genotype-specific physiological responses to salinity during early germination remain insufficiently characterized. Understanding variation among geographically distinct accessions is essential for identifying salt-tolerant genotypes. This study aimed to evaluate germination performance and antioxidant defense responses of three quinoa accessions of contrasting geographic origins under salinity stress. <b>Materials and Methods:</b> Three quinoa accessions 18GR (Ames 13724, USA), R-132 (PI 478418, Bolivia) and DE-1 (PI 674266, Ecuador) obtained from the USDA National Plant Germplasm System were evaluated under four NaCl concentrations (0, 100, 200 and 300 mM) under controlled laboratory conditions. Germination percentage, mean germination time (MGT), radicle length and germination kinetics were recorded. Reversibility assays were conducted to differentiate osmotic and ionic effects of salinity. Oxidative stress markers, including Hydrogen Peroxide (H<sub>2</sub>O<sub>2</sub>) and malondialdehyde (MDA), were quantified along with antioxidant enzyme activities such as peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX). Proline accumulation was also assessed as an indicator of osmotic adjustment. <b>Results:</b> Salinity significantly affected germination traits in an accession-dependent manner. At 300 mM NaCl, germination rates were 90, 60 and 33.33% for 18GR, R-132 and DE-1, respectively. Reversibility assays indicated osmotic stress predominance at 200 mM, while ionic toxicity dominated at higher concentrations. NaCl stress increased H<sub>2</sub>O<sub>2</sub> and MDA accumulation in all accessions. POD activity increased consistently across treatments. CAT and APX activities in 18GR showed a biphasic response, being stimulated up to 200 mM and inhibited at 300 mM, indicating stress threshold regulation. Proline accumulation increased with salinity, with 18GR showing the highest osmotic adjustment capacity. <b>Conclusion:</b> Geographic origin significantly influences salt tolerance during germination in quinoa. Accession 18GR exhibited superior stress tolerance and antioxidant regulation, making it a promising candidate for saline agriculture. The contrasting biochemical responses provide a physiological basis for selecting salt-tolerant quinoa genotypes adapted to arid and semi-arid environments.

PubMedBiochemistry and biophysics reports2026-10-15

A single amino acid mutation alters substrate specificity towards l-glucose in a bacterial l-galactose dehydrogenase.

Obara Nana N, Ito Chihiro C, Kawashita Keito K, Takenoya Mihoko M et al.

Structure-based mutagenesis was performed to modify the substrate specificity of bacterial l-galactose dehydrogenase from Luteolibacter sp. strain LG18, which also exhibits intrinsic l-glucose dehydrogenase activity. Based on previously reported crystal structures of the enzyme in ternary complex with l-galactose or l-glucose and NADP+, an M212Q mutant was generated and found to exhibit a pronounced preference for l-glucose. Kinetic analysis showed that the M212Q mutant displayed an approximately 20-fold higher k cat/K M value for l-glucose than for l-galactose. To elucidate the structural basis of this altered specificity, the X-ray crystal structure of the M212Q mutant complexed with l-glucose and NADP+ was determined. Substitution of Met212 with Gln is assumed to disrupt the hydrophobic environment between the residue and the substrates, which may prevent proper binding of l-galactose and resulting in an approximately 350-fold increase in K M compared with the wild type. In contrast, in the l-glucose-bound M212Q structure, a compensatory hydrogen bond is formed between the equatorial 4-OH group of l-glucose and Gln212, stabilizing substrate binding and reducing the K M value to approximately one-quarter of that of the wild type. Furthermore, a BLAST search with Lu-LGDH as a query resulted that homologs containing the glutamine residue at the corresponding position as well as other conserved catalytic and substrate-binding residues were found. With emerging studies on l-glucose biology, these results may contribute to enzymatic approaches for detecting the enzymes acting toward l-glucose, which is generally considered absent in nature.

PubMedNature communications2026-10-15

Compound Z247611722 Exhibits Antifungal Activity by Inhibiting Serine Palmitoyltransferase.

Nysten Jana J, Van Eynde Wout W, Lee Yunjin Y, Vanhoffelen Eliane E et al.

The global rise in fungal infections, driven by expanding at-risk populations and growing antifungal resistance, highlights the need for new therapies. However, the current antifungal arsenal remains limited and emerging resistance reduces treatment efficacy. Through high-throughput screening of 20,000 drug-like compounds, we identified Z56812898, a benzamide linked to a bicyclic pyrimidine-pyran trione with novel antifungal activity. Guided by this hit, we discovered a structural analog with improved antifungal potency, Z247611722. This fungicidal compound has novel antifungal activity against multiple Candida species and fluconazole-resistant isolates. Chemogenomic, metabolomic, and phenotypic analyses revealed that Z247611722 disrupts sphingolipid biosynthesis by targeting serine palmitoyltransferase (SPT). The mode of action was confirmed by experimental evolution, yielding a resistant strain with a non-synonymous mutation in the SPT-encoding gene, LCB2. Structural modelling localized this alanine-to-proline substitution adjacent to the catalytic cavity, where it could alter the dynamics and conformation of the binding pocket and impair compound accommodation. Importantly, Z247611722 demonstrates in vivo efficacy in an invertebrate model of C. albicans infection. These findings validate SPT as a promising target and introduce a structurally distinct sphingolipid biosynthesis inhibitor with therapeutic potential.

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