Request Demo

Last update 08 May 2025

IP6K1

Last update 08 May 2025

Basic Info

Synonyms

IHPK1, inositol hexakisphosphate kinase 1, Inositol hexaphosphate kinase 1

+ [3]

Introduction

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

Drugs associated with IP6K1

Inositol pyrophosphate IP7

Target

IP6K1

Mechanism

IP6K1 modulators

Active Org.

BioCrine AB

Originator Org.

BioCrine AB

Active Indication

Diabetes Mellitus, Type 2

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SCO-006

Target

IP6K1 x IP6K2 x IP6K3

Mechanism

IP6K1 inhibitors [+2]

Active Org.

SCOHIA PHARMA, Inc.

Originator Org.

Takeda Pharmaceutical Co., Ltd.

Active Indication

Ovarian clear cell carcinoma

Inactive Indication

Hyperphosphatemia

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

UNC7467

Target

IP6K1 x IP6K2

Mechanism

IP6K1 inhibitors [+1]

Active Org.

The University of North Carolina at Chapel Hill

Originator Org.

The University of North Carolina at Chapel Hill

Active Indication

Obesity

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with IP6K1

100 Translational Medicine associated with IP6K1

0 Patents (Medical) associated with IP6K1

282

Literatures (Medical) associated with IP6K1

01 Apr 2025·Diabetes

IP6K1 Rewires LKB1 Signaling to Mediate Hyperglycemic Endothelial Senescence

Article

Author: Xing, Changchang ; Chen, Alex F. ; Chin, Alfred C. ; Shi, Linhui ; Fiedler, Dorothea ; Qi, Ji ; Aguirre, Tim ; Zhu, Hong ; Zhu, Limei ; Chen, Yuanyuan ; Liu, Yue ; Fu, Chenglai

Diabetes is a major risk factor for cardiovascular disease, but the molecular mechanisms underlying diabetic vasculopathy have been elusive. Here we report that inositol hexakisphosphate kinase 1 (IP6K1) mediates hyperglycemia-induced endothelial senescence by rewiring liver kinase B1 (LKB1) signaling from the AMPK pathway to the p53 pathway. We found that hyperglycemia upregulated IP6K1, which disrupted Hsp/Hsc70 and carboxyl terminus of Hsc70-interacting protein–mediated LKB1 degradation, leading to increased expression levels of LKB1. High glucose also strengthened the binding of IP6K1 to AMPK, suppressing LKB1-mediated AMPK activation. Thus, elevated LKB1 did not lead to activation of the AMPK pathway. Instead, it bound more to p53, resulting in p53-dependent endothelial senescence. Endothelial cell–specific deletion of IP6K1 alleviated, whereas endothelial cell–specific overexpression of IP6K1 exaggerated, hyperglycemia-induced endothelial senescence. This study reveals a regulatory mechanism of IP6K1 in switching LKB1 activation of the AMPK pathway to activation of the p53 pathway. IP6K1 represents a potential therapeutic target for treating hyperglycemia-induced endothelial dysfunction.Article HighlightsDiabetes is a major risk factor for cardiovascular diseases. The mechanisms of hyperglycemia-induced endothelial dysfunction have been elusive. We found that inositol hexakisphosphate kinase 1 (IP6K1) mediates hyperglycemia-induced endothelial senescence by switching liver kinase B1 (LKB1) activation of the AMPK pathway to activation of the p53 pathway. Hyperglycemia upregulates IP6K1, which stabilizes LKB1 by disrupting Hsp/Hsc70 and carboxyl terminus of Hsc70-interacting protein–mediated LKB1 degradation but suppresses LKB1-dependent AMPK activation. Elevated LKB1 binds more to p53, resulting in p53-dependent endothelial senescence. Endothelial cell–specific deletion of IP6K1 attenuates, whereas endothelial cell–specific overexpression of IP6K1 exaggerates, hyperglycemia-induced endothelial senescence.

01 Feb 2025·Journal of Biological Chemistry

Inositol phosphates dynamically enhance stability, solubility, and catalytic activity of mTOR

Article

Author: Rameh, Lucia E ; York, John D ; Blind, Raymond D

Mechanistic target of rapamycin (mTOR) binds the small metabolite inositol hexakisphosphate (IP₆) as shown in structures of mTOR; however, it remains unclear if IP₆, or any other inositol phosphate species, function as an integral structural element(s) or catalytic regulator(s) of mTOR. Here, we show that multiple, exogenously added inositol phosphate species can enhance the ability of mTOR and mechanistic target of rapmycin complex 1 (mTORC1) to phosphorylate itself and peptide substrates in in vitro kinase reactions, with the higher order phosphorylated species being more potent (IP₆ = IP₅ > IP₄ >> IP₃). IP₆ increased the V_MAX and decreased the apparent K_M of mTOR for ATP. Although IP₆ did not affect the apparent K_M of mTORC1 for ATP, monitoring kinase activity over longer reaction times showed increased product formation, suggesting inositol phosphates stabilize the active form of mTORC1 in vitro. The effects of IP₆ on mTOR were reversible, suggesting IP₆ bound to mTOR can be exchanged dynamically with the free solvent. Interestingly, we also observed that IP₆ could alter mTOR electrophoretic mobility under denaturing conditions and its solubility in the presence of manganese. Together, these data suggest for the first time that multiple inositol phosphate species (IP₆, IP₅, IP₄, and to a lesser extent IP₃) can dynamically regulate mTOR and mTORC1 by promoting a stable, more soluble active state of the kinase. Our data suggest that studies of the dynamics of inositol phosphate regulation of mTOR in cells are well justified.

01 Jan 2025·Protein Science

Effects of allosteric effectors on oxygen binding to crystals of hemoglobin in the R‐quaternary structure

Article

Author: Shibayama, Naoya

AbstractMuch is known about how allosteric effectors influence the equilibrium between the relaxed (R) and tense (T) states of hemoglobin (Hb), but little is known about how and to what extent the effectors lower the intrinsic O2 affinity of each allosteric state, especially the R‐state. Here, we provide a thorough characterization of the O2 equilibria of effector‐bound and unbound R‐quaternary form crystals of horse Hb without a quaternary structural switching. In the absence of effectors, R crystals of horse Hb were shown to bind O2 noncooperatively with a very high affinity virtually identical to that of R crystals of human Hb. We found that the effector bezafibrate (BZF) and its derivative L35 lower the overall O2 affinity of R crystals by approximately a factor of 3 and 2, respectively, while both maintaining noncooperative oxygenation. These effects are observed regardless of whether the effectors are co‐crystallized or soaked into the effector‐free protein crystals with a different lattice, confirming that the observed affinity reduction is induced by the BZF derivatives and not by crystal packing forces. Our findings, combined with available co‐crystal structural data, suggest that the BZF derivatives lower the O2 affinity of the R‐quaternary structure of Hb through structural constraints imposed by a quaternary shift slightly toward T. Additionally, since no co‐crystal of R‐state Hb with the effector inositol hexakisphosphate (IHP) is available, we only present an IHP‐soaking experiment showing little change in O2 affinity, and poor IHP binding to the R crystal structure of horse Hb is suggested.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

IP6K1

Basic Info

Related

Analysis