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

✓ Approved

Kotobuki Pharmaceutical Co., Ltd. · DPP4 · 小分子

什么是 sitagliptin phosphate + ipragliflozin L-proline？

sitagliptin phosphate + ipragliflozin L-proline 是一种小分子，由Kotobuki Pharmaceutical Co., Ltd.研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

商品名Sujanu, MK0431J
公司Kotobuki Pharmaceutical Co., Ltd.
药物类别小分子
分子靶点DPP4, SLC5A2
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Kotobuki Pharmaceutical Co., Ltd.

作用机制

分子靶点

sitagliptin phosphate + ipragliflozin L-proline 作用于 2 个分子靶点：

DPP4dipeptidyl peptidase 4 (CD26, DPPIV)
SLC5A2solute carrier family 5 member 2 (SGLT2)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

sitagliptin phosphate + ipragliflozin L-proline 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Metabolism and nutrition disordersType 2 diabetes mellitus✓ Approved

相关研究文献

PubMedOrganic letters2026-07-27

Dual Photoredox/NHC Catalysis with a Renewable Feedstock: Accessing Quaternary γ-Amino Ketones from Proline.

Hou Xuewei X, Ma Ruiying R, Yuan Fei F, Liu Yuxiu Y et al.

A mild and efficient dual photoredox/NHC catalytic system is developed for the synthesis of γ-amino ketones from naturally sourced proline derivatives, alkenes, and aryl carboxylic acids. This three-component radical coupling constructs two new C-C bonds in a single operation, affording a range of quaternary γ-amino ketones in moderate to excellent yields with broad substrate scope and good functional group tolerance. The reaction operates under mild, room-temperature conditions and uses renewable proline feedstocks. Gram-scale synthesis further demonstrates the scalability and practicality of this green protocol.

PMID 42503701
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PubMed3 Biotech2026-07-27

Characterization of drought tolerance traits in Ahl15gr inducible transgenic Nicotiana tabacum L. (Solanaceae).

Shakeel Zindagi Z, Khan Majid M, Din Israr Ud IU, Khan Muhammad Nauman MN et al.

Stress influences plant growth and development, although beneficial in adoptive mechanisms but usually negatively affect production. The molecular response of plants to drought stress involves complex regulatory mechanisms which mainly involve changes in the transcriptional activity of stress-related genes. Transgenic plants provide critical insights to investigate the function of these genes. AT-HOOK MOTIF NUCLEAR LOCALIZED PROTEIN (AHL15)is one of these genes which modulate plant morphology and developmental processes in Arabidopsis and tobacco. In this study, we evaluated the drought stress resistance of inducible AHL15GR transgenic N. tabacum by withholding water for 25 days. Our results show that shoot length and leaf size were reduced in the AHL15GR transgenic plants both before and after drought stress in the case of DEX activation compared to the wild type and Non-DEX treated AHL15GR transgenic tobacco plants (control). The chlorophyll content was significantly higher in the transgenic plants (13 mg/g and 17 mg/g) than in the wild-type plants (7 mg/g and 9 mg/g) during and after drought stress, respectively. Similarly, a significant increase in proline content was observed in DEX-treated AHL15GR transgenic tobacco plants (3.3µmoL/g and 2.7µmoL/g) as compared to wild-type plants (2.1µmoL/g and 1.9µmoL/g).The highest relative water content (RWC) was observed in AHL15GR transgenic plants before drought stress. Before drought stress, the RWC in DEX-induced AHL15GR transgenic tobacco plants was 60% compared to wild-type plants (35%), while after stress, an RWC of 50% was observed in DEX-activated AHL15GR transgenic plants compared to wild-type plants (40%). The increase in proline content, maintenance of chlorophyll and percentage RWC confirm that the AHL15 gene induces drought resistance in the AHL15GR transgenic tobacco plants. These findings highlight a gene-driven pathway to build climate-resilient crops, which is essential for ensuring food security and sustainability in water-scarce regions.

PMID 42504274
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PubMedMetabolites2026-07-27

Plasma Aromatic L-Amino Acid Decarboxylase Activity by HPLC as a Functional Biomarker for the Diagnosis of Aromatic L-Amino Acid Decarboxylase Deficiency.

Mohamed Shakrin Norashareena N, Khalid Norzahidah N, Abdul Azize Nor Azimah NA, Yakob Yusnita Y et al.

Background/Objectives: Aromatic L-amino acid decarboxylase deficiency (AADC-D; OMIM #608643) is a rare autosomal recessive neurometabolic disorder caused by pathogenic variants in the DDC gene, leading to impaired of monoamine neurotransmitter biosynthesis. AADC, a pyridoxal-5'-phosphate (PLP)-dependent enzyme, catalyzes the conversion of L-dopa and 5-hydroxytryptophan (5-HTP) to dopamine and serotonin, respectively. Early diagnosis remains challenging due to the limited specificity of current biochemical approaches. This study aimed to evaluate plasma AADC enzyme activity using these physiological substrates by High-Performance Liquid Chromatography (HPLC)-based method and assess its potential utility in the biochemical diagnosis of AADC deficiency. Methods: Plasma AADC activity was quantified using physiological substrates (L-dopa and 5-HTP) by HPLC with electrochemical and fluorescence detection. Sanger sequencing of the DDC gene was performed in two suspected patients to identify pathogenic variants. Results: Two genetically confirmed AADC-D patients demonstrated reduced enzyme activity. Using L-dopa as substrate, enzyme activity in patients was 12.4 and 26.1 pmol/min/mL, both below the published reference interval (36-129 pmol/min/mL). Using 5-HTP as substrate, enzyme activity was 1.5 and 5.1 pmol/min/mL; Patient 1 showed activity below the reference interval (2.0-7.1 pmol/min/mL), while Patient 2 demonstrated activity within the lower range of reported values. Reduced enzyme activity was consistent with the clinical features and molecular findings with identification of pathogenic variants in the DDC gene (c.175G>A and c.714+4A>T). Conclusions: Plasma AADC activity measurement demonstrates potential as a functional biochemical biomarker that augments molecular genetic testing in the biochemical evaluation of AADC deficiency. Further studies involving larger patient cohorts are required to further evaluate its diagnostic performance and broader clinical applicability.

PMID 42506398
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PubMedGels (Basel, Switzerland)2026-07-27

A Dual-Functional Zr-Ion Crosslinked PVA-Alginate Hydrogel with Embedded ZrMgFe-LDH for Enhanced Phosphate Recovery.

Tang Fengqin F, Xiong Runwen R, Zou Shiqi S, Ma Xiaomei X et al.

Excess phosphate in aquatic environments can trigger eutrophication and pose risks to ecosystem integrity and public health, even though phosphate is indispensable for plant growth. Herein, we report the fabrication of Zr-LDHs-PS hydrogel microspheres by in situ cross-linking zirconium-magnesium-iron layered double hydroxides (ZrMgFe-LDHs) with Polyvinyl alcohol (PVA) and sodium alginate (SA). The resulting bead-type adsorbent was designed to enable efficient phosphate capture from water while facilitating subsequent, controlled phosphate release. Benefiting from the cross-linking granulation strategy, the microspheres mitigate typical limitations of powdered adsorbents, including compaction, aggregation, and poor separability. General characterization (SEM, FT-IR, XPS, XRD, BET, TG, and zeta potential) elucidated the microstructure and surface chemical composition. The Zr-LDHs-PS microspheres exhibited a maximum experimental adsorption capacity of 51.313 mg/g. Kinetics data were best fitted by the pseudo-second-order model, and adsorption isotherms were subjected to the Freundlich model, pointing to heterogeneous, multilayer adsorption. Importantly, high phosphate selectivity was preserved despite the coexistence of competing anions (Cl-, NO3-, and CO32-). After adsorption, the spent beads released phosphate gradually in water, highlighting their potential for dual functionality. Collectively, these results demonstrate that Zr-LDHs-PS hydrogel microspheres are promising candidates for extraction-based phosphate removal and resource recovery, with prospects for repurposing slow-release phosphate fertilizers to support sustainable plant nutrition.

PMID 42505254
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PubMedMetabolites2026-07-27

A Two-Layer Structural Key Framework for Linking Compound Identifiers and MS/MS Evidence in Spectral Database Curation.

Deng Kaiwen K, Liu Ran R, He Ruiping R, Chen Li L

Background: MS/MS spectral databases provide reference spectra for compound identification in metabolomics studies. Their utility depends on clear links among compound identifiers, chemical structures, and MS/MS evidence, yet these links are often complicated by database-specific identifiers, heterogeneous structural representations, and stereochemical specifications. Methods: Here, we present a two-layer structural key framework for linking compound identifiers and MS/MS evidence through standardized structures. Reported SMILES were standardized and converted into InChIKey-derived stereo keys and connectivity keys using a Python-based RDKit workflow. Results: As illustrated using stereoisomeric cases such as L- and D-proline, the stereo key layer preserves compound identifiers and metadata at the stereo level, whereas the connectivity key layer groups comparable MS/MS evidence at the molecular connectivity level. In a database-scale application, 217,920 HMDB compound entries were organized into 216,783 stereo keys and 196,512 connectivity keys, and 144,591 spectra from the spectrum-centered MoNA database were incorporated into the HMDB-centered framework, increasing MS/MS evidence coverage, particularly at the molecular connectivity level. Conclusions: Together, this framework links compound identifiers, standardized structures, and MS/MS evidence at the stereo and connectivity levels, providing a bidirectionally traceable system for spectral database curation without forcing connectivity-level MS/MS evidence into stereo-specific compound identities.

PMID 42506389
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PubMedMetabolites2026-07-27

Plasma 4-Hydroxyproline Levels Are Associated with Diabetes in Chinese Adults: A Cross-Sectional Analysis.

Huang Qiaoliang Q, Mu Yingjun Y, Ma Ruirui R, Zhu Jiayao J et al.

4-Hydroxyproline, a product of collagen turnover generated through prolyl hydroxylation, has been implicated in metabolic regulation. While previous studies have associated circulating proline with diabetes, the relationship between 4-hydroxyproline and diabetes remains unclear. We conducted a cross-sectional analysis of 796 adults aged 35-74 years from Changshu, eastern China. Plasma 4-hydroxyproline levels were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Higher plasma 4-hydroxyproline levels were associated with increased odds of diabetes after multivariable adjustment (per SD increase: OR = 1.35, 95% CI: 1.10-1.66; p = 0.004). Participants in the highest quartile had higher odds of diabetes than those in the lowest quartile (Q4 vs. Q1: OR = 1.86, 95% CI: 1.01-3.47; p for trend = 0.006). The associations remained materially unchanged after excluding insulin users, individuals with diabetes-related complications, and those using antidiabetic medication. Further adjustment for dietary intake and proline did not materially alter the results. Higher plasma 4-hydroxyproline levels were associated with diabetes. Given the cross-sectional design, causality cannot be inferred, and reverse causation cannot be excluded. Prospective studies are needed to confirm these findings.

PMID 42506420
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