Last update 01 Nov 2024

PIP4K2A x PIP4K2C

Last update 01 Nov 2024

Basic Info

Related Targets

PIP4K2APIP4K2C

Drugs associated with PIP4K2A x PIP4K2C

ARUK2007145

Target

PIP4K2A x PIP4K2C

Mechanism

PIP4K2A inhibitors [+1]

Active Org.

University of Cambridge

Originator Org.

University of Cambridge

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

TM-04-168-03

Target

PIP4K2A x PIP4K2B x PIP4K2C

Mechanism

PIP4K2A inhibitors [+2]

Active Org.-

Originator Org.-

Active Indication-

Inactive Indication-

Drug Highest Phase-

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PIP4K2A x PIP4K2C

100 Translational Medicine associated with PIP4K2A x PIP4K2C

0 Patents (Medical) associated with PIP4K2A x PIP4K2C

Literatures (Medical) associated with PIP4K2A x PIP4K2C

01 Aug 2024·European Journal of Pharmacology

Potency and efficacy of pharmacological PIP4K2 inhibitors in acute lymphoblastic leukemia

Article

Author: Machado-Neto, João Agostinho ; Lima, Keli ; Velloso, Elvira Deolinda Rodrigues Pereira ; da Silva, Wellington Fernandes ; Cipelli, Marcella ; Leal, Aline de Medeiros ; Schuringa, Jan Jacob ; Câmara, Niels Olsen Saraiva ; Pereira-Martins, Diego Antonio ; Nogueira, Frederico Lisboa ; Carvalho, Maria Fernanda Lopes ; Nardinelli, Luciana ; Bendit, Israel ; Cavaglieri, Rita de Cássia ; Rego, Eduardo Magalhães

Acute lymphoblastic leukemia (ALL), a complex malignancy, displays varying expression profiles of PIP4K2-related genes in adult patients. While PIP4K2A expression is elevated in ALL bone marrow cells compared to healthy bone marrow cells, PIP4K2B is downregulated, and PIP4K2C remains relatively unchanged. Despite the correlation between increased PIP4K2A expression and increased percentage of peripheral blood blasts, clinical outcomes do not strongly correlate with the expression of these genes. Here we investigated the therapeutic potential of three PIP4K2 inhibitors (THZ-P1-2, a131, and CC260) in ALL cell models. THZ-P1-2 emerges as the most effective inhibitor, inducing cell death and mitochondrial damage while reducing cell viability and metabolism significantly. Comparative analyses highlight the superior efficacy of THZ-P1-2 over a131 and CC260. Notably, THZ-P1-2 uniquely disrupts autophagic flux and inhibits the PI3K/AKT/mTOR pathway, indicating a distinct molecular mechanism. In summary, our findings elucidate the differential expression of PIP4K2-related genes in ALL and underscore the potential role of PIP4K2A in disease pathogenesis. The therapeutic promise of THZ-P1-2 in ALL treatment, along with its distinct effects on cell death mechanisms and signaling pathways, enriches our understanding of PIP4K2's involvement in ALL development and offers targeted therapy prospects.

01 Dec 2021·BMC Medical GenomicsQ4 · MEDICINE

Signature RNAS and related regulatory roles in type 1 diabetes mellitus based on competing endogenous RNA regulatory network analysis

Q4 · MEDICINE

ArticleOA

Author: Yao, Hanxin ; Shi, Qinghong

AbstractBackgroundOur study aimed to investigate signature RNAs and their potential roles in type 1 diabetes mellitus (T1DM) using a competing endogenous RNA regulatory network analysis.MethodsExpression profiles of GSE55100, deposited from peripheral blood mononuclear cells of 12 T1DM patients and 10 normal controls, were downloaded from the Gene Expression Omnibus to uncover differentially expressed long non-coding RNAs (lncRNAs), mRNAs, and microRNAs (miRNAs). The ceRNA regulatory network was constructed, then functional and pathway enrichment analysis was conducted. AT1DM-related ceRNA regulatory network was established based on the Human microRNA Disease Database to carry out pathway enrichment analysis. Meanwhile, the T1DM-related pathways were retrieved from the Comparative Toxicogenomics Database (CTD).ResultsIn total, 847 mRNAs, 41 lncRNAs, and 38 miRNAs were significantly differentially expressed. The ceRNA regulatory network consisted of 12 lncRNAs, 10 miRNAs, and 24 mRNAs. Two miRNAs (hsa-miR-181a and hsa-miR-1275) were screened as T1DM-related miRNAs to build the T1DM-related ceRNA regulatory network, in which genes were considerably enriched in seven pathways. Moreover, three overlapping pathways, including the phosphatidylinositol signaling system (involving PIP4K2A, INPP4A, PIP4K2C, and CALM1); dopaminergic synapse (involving CALM1 and PPP2R5C); and the insulin signaling pathway (involving CBLB and CALM1) were revealed by comparing with T1DM-related pathways in the CTD, which involved four lncRNAs (LINC01278, TRG-AS1, MIAT, and GAS5-AS1).ConclusionThe identified signature RNAs may serve as important regulators in the pathogenesis of T1DM.

01 Feb 2021·Journal of Comparative NeurologyQ3 · MEDICINE

Distribution and localization of phosphatidylinositol 5‐phosphate, 4‐kinase alpha and beta in the brain

Q3 · MEDICINE

Article

Author: Cantley, Lewis C. ; Milner, Teresa A. ; Noch, Evan K. ; Yim, Isaiah

AbstractPhosphatidylinositol‐4,5‐bisphosphate (PI‐4,5‐P2) is critical for synaptic vesicle docking and fusion and generation of the second messengers, diacylglycerol and inositol‐1,4,5‐trisphosphate. PI‐4,5‐P2 can be generated by two families of kinases: type 1 phosphatidylinositol‐4‐phosphate 5‐kinases, encoded by PIP5K1A, PIP5K1B and PIP5K1C, and type 2 phosphatidylinositol‐5‐phosphate 4‐kinases, encoded by PIP4K2A, PIP4K2B, and PIP4K2C. While the roles of the type 1 enzymes in brain function have been extensively studied, the roles of the type 2 enzymes are poorly understood. Using selective antibodies validated by genetic deletion of pip4k2a or pip4k2b in mouse brain, we characterized the location of the enzymes, PI5P4Kα and PI5P4Kβ, encoded by these genes. In mice, we demonstrate that PI5P4Kα is expressed in adulthood, whereas PI5P4Kβ is expressed early in development. PI5P4Kα localizes to white matter tracts, especially the corpus callosum, and at a low level in neurons, while PI5P4Kβ is expressed in neuronal populations, especially hippocampus and cortex. Dual labeling studies demonstrate that PI5P4Kα co‐localizes with the oligodendrocyte marker, Olig2, whereas PI5P4Kβ co‐localizes with the neuronal marker, NeuN. Ultrastructural analysis demonstrates that both kinases are contained in axon terminals and dendritic spines adjacent to the synaptic membrane, which support a potential role in synaptic transmission. Immunoperoxidase analysis of macaque and human brain tissue demonstrate a conserved pattern for PI5P4Kα and PI5P4Kβ. These results highlight the diverse cell‐autonomous expression of PI5P4Kα and PI5P4Kβ and support further exploration into their role in synaptic function in the brain.

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