Last update 01 Nov 2024

APAF1

Last update 01 Nov 2024

Basic Info

Synonyms

APAF-1, APAF1, apoptotic peptidase activating factor 1

+ [3]

Introduction

Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP. Isoform 6 is less effective in inducing apoptosis.

Drugs associated with APAF1

LPT-99

Target

APAF1

Mechanism

APAF1 inhibitors

Active Org.

Loop Therapeutics, Inc.Startup [+1]

Originator Org.

Loop Therapeutics, Inc.Startup

Active Indication

Hearing Loss

Inactive Indication

Deafness

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SVT-AP-99

Target

APAF1

Mechanism

APAF1 inhibitors

Active Org.-

Originator Org.

Laboratorios Salvat SA

Active Indication-

Inactive Indication

Ear Diseases

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

LPT-98

Target

APAF1

Mechanism

APAF1 inhibitors

Active Org.-

Originator Org.

Loop Therapeutics, Inc.Startup

Active Indication-

Inactive Indication

Keratoplasty rejection

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with APAF1

ACTRN12618001461280 / CompletedPhase 1

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Studyto Evaluate the Safety and Tolerability of LPT99 Administered to Healthy Adult Subjects

Start Date25 Sep 2018

Sponsor / Collaborator

Spiral Therapeutics, Inc.Startup

100 Clinical Results associated with APAF1

100 Translational Medicine associated with APAF1

0 Patents (Medical) associated with APAF1

2,247

Literatures (Medical) associated with APAF1

16 Dec 2024·Animal Biotechnology

Detection of polymorphisms in six genes and their association analysis with litter size in sheep

Article

Author: Liu, Kai ; Chu, Mingxing ; Liu, Yufang

Litter size in sheep is a complex trait controlled by micro-effective polygenes. APAF1, CLSTN2, CTH, PLCB1, PLCB4, and CHST11 are all involved in mammalian reproduction. However, the effects of these genes on litter size in sheep are still unclear. Therefore, in this study, we used Sequenom MassARRAY® SNP assay technology to type the single nucleotide polymorphisms (SNPs) loci of six genes in five sheep breeds. The results showed that most sheep breeds contain three genotypes at each locus. Then, we conducted population genetic analysis on the SNPs of six genes and found that the polymorphic information content in all sheep breeds ranged from 0 to 0.37, and most sheep breeds were in Hardy-Weinberg equilibrium (p > 0.05). In addition, association analysis in Small Tail Han sheep indicated that the rs399534524 locus in CLSTN2 was highly associated with first parity litter size, and litter size in ewes with CT genotype was higher than that in ewes with CC genotype or TT genotype. Furthermore, the rs407142552 locus in CTH was highly associated with second parity litter size in Small Tail Han sheep, and litter size in ewes with CT genotype was higher than that in ewes with TT genotype. Finally, we predicted the CTH and CLSTN2 protein interaction network and found that HTR1E, NOM1, CCDC174 and ALPK3 interact with CLSTN2 and have been reported as candidate genes related to litter size in sheep. These results suggest that they may be useful genetic markers for increasing litter size in sheep.

11 Dec 2024·Journal of Biomolecular Structure and Dynamics

Withania somnifera extract reduces gastric cancerous properties through inhibition of gankyrin in cellular milieu produced by Helicobacter pylori and Epstein Barr virus

Article

Author: Kumar, Sachin ; Baral, Budhadev ; Jha, Hem Chandra ; Bagde, Pranit Hemant ; Kashyap, Dharmendra ; Roy, Rajarshi ; Kar, Parimal ; Varshney, Nidhi ; Kandpal, Meenakshi

Helicobacter pylori and Epstein Barr virus (EBV) are group1 carcinogens and their role in Gastric cancer (GC) is well established. Previously we have shown that H. pylori and EBV appears to support aggressive gastric oncogenesis through the upregulation of oncoprotein Gankyrin. Natural plant active molecules have the potential to interrupt oncogenesis. Herein, we investigated the potential of Withania somnifera root extract (WSE) as a possible chemotherapeutic agent against host oncoprotein Gankyrin whose expression was altered by H. pylori and EBV-associated modified cellular milieu. The results show that WSE does not have any inhibitory effect on H. pylori and EBV-associated gene transcripts except for the lmps (lmp1, lmp2a, and lmp2B). Moreover, the WSE exert their anticancer activity via host cellular response and decreased the expression of cell-migratory (mmp3 and mmp7); cell-cycle regulator (pcna); antiapoptotic gene (bcl2); increased the expression of the proapoptotic gene (apaf1 and bax); and tumor suppressor (p53, prb, and pten). Knockdown of Gankyrin followed by the treatment of WSE also decreases the expression of TNF-ɑ, Akt, and elevated the expression of NFkB, PARP, Casp3, and Casp9. WSE also reduces cell migration, and genomic instability and forced the cells to commit programmed cell death. Moreover, molecular simulation studies revealed that out of eight active compounds of WSE, only four compounds such as withaferin A (WFA), withanoside IV (WA4), withanolide B (WNB), and withanolide D (WND) showed direct stable interaction with Gankyrin. This article reports for the first time that treatment of WSE decreased the cancerous properties through host cellular response modulation in gastric epithelial cells coinfected with H. pylori and EBV.Communicated by Ramaswamy H. Sarma.

01 Nov 2024·Environmental Toxicology

Naringin Induces ROS‐Stimulated G₁ Cell‐Cycle Arrest and Apoptosis in Nasopharyngeal Carcinoma Cells

Article

Author: Yao, Chun‐Hsu ; Chen, Chan‐Hung ; Pandey, Sudhir ; Bau, Da‐Tian ; Tien, Ni ; Lin, Meng‐Liang ; Hseu, You‐Cheng ; Chen, Shih‐Shun ; Yang, Hsin‐Ling ; Chen, Siang‐Jyun

ABSTRACTNaringin, a bioflavonoid compound from grapefruit or citrus, exerts anticancer activities on cervical, thyroid, colon, brain, liver, lung, thyroid, and breast cancers. The present investigation addressed exploring the anticancer effects of naringin on nasopharyngeal carcinoma (NPC) cells. Naringin exhibits a cytotoxic effect on NPC‐TW 039 and NPC‐TW 076 cells with IC50 372/328 and 394/307 μM for 24 or 48 h, respectively, while causing little toxicity toward normal gingival epithelial (SG) cells (>500/500 μM). We established that naringin triggered G1 arrest is achieved by suppressing cyclin D1, cyclin A, and CDK2, and upregulating p21 protein in NPC cells. Exposure of NPC cells to naringin caused a series of events leading to apoptosis including morphology change (cell shrinkage and membrane blebbing) and chromatin condensation. Annexin V and PI staining indicated that naringin treatment promotes necrosis and late apoptosis in NPC cells. DiOC6 staining showed a decline in the mitochondrial membrane potential by naringin treatment, which was followed with cytochrome c release, Apaf‐1/caspase‐9/‐3 activation, PARP cleavage, and EndoG expression in NPC cells. Naringin upregulated proapoptotic Bax and decreased antiapoptotic Bcl‐xL expression, and dysregulated Bax/Bcl‐xL ratio in NPC cells. Notably, naringin enhanced death receptor‐related t‐Bid expression. Furthermore, an increased Ca2+ release by naringin treatment which instigated endoplasmic reticulum stress‐associated apoptosis through increased IRE1, ATF‐6, GRP78, GADD153, and caspase‐12 expression in NPC cells. In addition, naringin triggers ROS production, and inhibition of naringin‐induced ROS generation by antioxidant N‐acetylcysteine resulted in the prevention of G1 arrest and apoptosis in NPC cells. Naringin‐induced ROS‐mediated G1 arrest and mitochondrial‐, death receptor‐, and endoplasmic reticulum stress–mediated apoptosis may be a promising strategy for treating NPC.

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APAF1

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