更新于：2024-11-01

IP6K1

更新于：2024-11-01

基本信息

别名

IHPK1、inositol hexakisphosphate kinase 1、Inositol hexaphosphate kinase 1

+ [3]

简介

Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5). Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.

关联

项与 IP6K1 相关的药物

UNC7467

靶点

IP6K1 x IP6K2

作用机制

IP6K1抑制剂 [+1]

在研机构

The University of North Carolina at Chapel Hill

原研机构

The University of North Carolina at Chapel Hill

在研适应症

肥胖

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

SCO-006

靶点

IP6K1 x IP6K2 x IP6K3

作用机制

IP6K1抑制剂 [+2]

在研机构

SCOHIA PHARMA, Inc.初创企业

原研机构

Takeda Pharmaceutical Co., Ltd.

在研适应症

卵巢透明细胞癌

非在研适应症

高磷血症

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

Inositol pyrophosphate IP7

靶点

IP6K1

作用机制

IP6K1 modulators

在研机构

BioCrine AB

原研机构

BioCrine AB

在研适应症

2型糖尿病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 IP6K1 相关的临床结果

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100 项与 IP6K1 相关的转化医学

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0 项与 IP6K1 相关的专利（医药）

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354

项与 IP6K1 相关的文献（医药）

2024-11-01·Biological Trace Element Research

Impact of Trace Mineral Source and Phytase Supplementation on Prececal Phytate Degradation and Mineral Digestibility, Bone Mineralization, and Tissue Gene Expression in Broiler Chickens

Article

作者: Monteiro, Alessandra ; Sommerfeld, Vera ; Philippi, Hanna ; Olukosi, Oluyinka A ; Rodehutscord, Markus

AbstractThe objective of this study was to determine how different sources of Zn, Mn, and Cu in the feed without and with phytase affect prececal myo-inositol hexakisphosphate (InsP6) breakdown to myo-inositol (MI), prececal P digestibility, bone mineralization, and expression of mineral transporters in the jejunum of broiler chickens. A total of 896 male broiler chicks (Cobb 500) were distributed to 7 diets with 8 replicate pens (16 birds per floor pen). Experimental diets were fed from day 0 to 28. Diets were without or with phytase supplementation (0 or 750 FTU/kg) and were supplemented with three different trace mineral sources (TMS: sulfates, oxides, or chelates) containing 100 mg/kg Zn, 100 mg/kg Mn, and 125 mg/kg Cu. Prececal InsP6 disappearance and P digestibility were affected by interaction (phytase × TMS: P ≤ 0.010). In diets without phytase supplementation, prececal InsP6 disappearance and P digestibility were greater (P ≤ 0.001) in birds fed chelated minerals than in birds fed sulfates or oxides. However, no differences were observed between TMS in diets with phytase supplementation. Ileal MI concentration was increased by exogenous phytase but differed depending on TMS (phytase × TMS: P ≤ 0.050). Tibia ash concentration as well as Zn and Mn concentration in tibia ash were increased by phytase supplementation (P < 0.010), but the Cu concentration in tibia ash was not (P > 0.050). Gene expression of the assayed mineral transporters in the jejunum was not affected by diet (P > 0.050), except for Zn transporter 5 (phytase × TMS: P = 0.024). In conclusion, the tested TMS had minor effects on endogenous phytate degradation in the digestive tract of broiler chickens. However, in phytase-supplemented diets, the choice of TMS was not relevant to phytate degradation under the conditions of this study.

2024-10-30·Bioscience Reports

Interaction with IP6K1 supports pyrophosphorylation of substrate proteins by the inositol pyrophosphate 5-InsP7

Article

作者: Pal, Monisita ; Ladke, Jayashree S. ; Shah, Akruti ; Hamid, Aisha ; Bhandari, Rashna ; Singh, Arpita ; Ganguli, Shubhra

AbstractInositol pyrophosphates (PP-InsPs) are a sub-family of water soluble inositol phosphates that possess one or more diphosphate groups. PP-InsPs can transfer their β-phosphate group to a phosphorylated Ser residue to generate pyrophosphorylated Ser. This unique post-translational modification occurs on Ser residues that lie in acidic stretches within an intrinsically disordered protein sequence. Serine pyrophosphorylation is dependent on the presence of Mg2+ ions, but does not require an enzyme for catalysis. The mechanisms by which cells regulate PP-InsP-mediated pyrophosphorylation are still unknown. We performed mass spectrometry to identify interactors of IP6K1, an enzyme responsible for the synthesis of the PP-InsP 5-InsP7. Interestingly, IP6K1 interacted with several proteins that are known to undergo 5-InsP7-mediated pyrophosphorylation, including the nucleolar proteins NOLC1, TCOF and UBF1, and AP3B1, the β subunit of the AP3 adaptor protein complex. The IP6K1 interactome also included CK2, a protein kinase that phosphorylates Ser residues prior to pyrophosphorylation. We observe the formation of a protein complex between IP6K1, AP3B1, and the catalytic α-subunit of CK2, and show that disrupting IP6K1 binding to AP3B1 lowers its in vivo pyrophosphorylation. We propose that assembly of a substrate-CK2-IP6K complex would allow for coordinated pre-phosphorylation and pyrophosphorylation of the target serine residue, and provide a mechanism to regulate this enzyme-independent modification.

2024-09-26·Journal of Medicinal Chemistry

Structure–Activity Relationship of Inositol Thiophosphate Analogs as Allosteric Activators of Clostridioides difficile Toxin B

Article

作者: Castagner, Bastien ; Vasegh, Seyed Ehsan ; Keogh, Liam ; Veyron, Simon ; Trempe, Jean-François ; Grosjean, Félix ; Cummer, Rebecca ; Bolteau, Raphaël

Clostridioides difficile is a bacterium that causes life-threatening intestinal infections. Infection symptoms are mediated by a toxin secreted by the bacterium. Toxin pathogenesis is modulated by the intracellular molecule, inositol-hexakisphosphate (IP6). IP6 binds to a cysteine protease domain (CPD) on the toxin, inducing autoproteolysis, which liberates a virulence factor in the cell cytosol. We developed second-generation IP6 analogs designed to induce autoproteolysis in the gut lumen, prior to toxin uptake, circumventing pathogenesis. We synthesized a panel of thiophosphate-/sulfate-containing IP6 analogs and characterized their toxin binding affinity, autoproteolysis induction, and cation interactions. Our top candidate was soluble in extracellular cation concentrations, unlike IP6. The IP6 analogs were more negatively charged than IP6, which improved affinity and stabilization of the CPD, enhancing toxin autoproteolysis. Our data illustrate the optimization of IP6 with thiophosphate biomimetic which are more capable of inducing toxin autoproteolysis than the native ligand, warranting further studies in vivo.