death

Programmed cell death in bacteria is dependent on a system of cell-to-cell communication termed quorum sensing. Extracellular death factor (EDF) is a linear pentapeptide that communicating cells produce and release, which upon reaching a sufficient concentration activates the cell death pathway in a subset of cells. It is sensitive to extreme pH, high temperatures, and other stressful conditions. At 2.5 ng/ml, EDF has been shown to facilitate mazEF-mediated cell death, significantly reducing population size in E. coli cultures.

BzATP triethylammonium salt is a P2X7 receptor agonist.

DAPK Substrate Peptide acetate is a death-associated protein kinase (DAPK, Km = 9 μM) peptide substrate.

Calcineurin Autoinhibitory Peptide acetate is a selectivecalcineurin phosphatase inhibitor(IC50 ~ 10 μM). Calcineurin Autoinhibitory Peptide acetate can be used in the protection of neurons from excitatory neuronal death.

Peptide5 acetate reduces animal swelling, astrogliosis, and neuronal cell death after spinal cord injury. Peptide5 acetate significantly reduces the degree of spinal cord injury (SCI) in a rodent ex vivo model.

Pegsebrenatide (NLY01), a long-acting GLP-1R agonist, exhibits an extended half-life and favorable blood-brain barrier penetration. It impedes A1 astrocyte transformation, mitigates dopaminergic cell death, and ameliorates motor symptoms in mouse models of Parkinson's disease (PD) [1].

KLA peptide is a cationic amphipathic mitochondrial membrane-disrupting peptide that can induce programmed cell death by targeting mitochondrial membranes, yet it lacks the ability to transverse the plasma membrane.

This peptide, generated from the BH3 domain of Bak (Flu-BakBH3), has been shown to have high-affinity binding to a surface pocket of the Bcl-XL protein that is required for its death antagonist function.

This peptide is a potent humanin (HN) derivative. It completely suppresses neuronal cell death by Alzheimer's disease-relevant insults.

α-Melanocyte-stimulating hormone (α-MSH) is a 13-amino acid peptide hormone produced by post-translational processing of proopiomelanocortin (POMC) in the pituitary gland, as well as in keratinocytes, astrocytes, monocytes, and gastrointestinal cells.1It is an agonist of melanocortin receptor 3 (MC3R) and MC4R that induces cAMP production in Hepa cells expressing the human receptors (EC50s = 0.16 and 56 nM, respectively).2α-MSH (100 pM) reducesS. aureuscolony formation andC. albicansgerm tube formationin vitro.3It inhibits endotoxin-, ceramide-, TNF-α-, or okadaic acid-induced activation of NF-κB in U937 cells.1α-MSH reduces IL-6- or TNF-α-induced ear edema in mice.4It also prevents the development of adjuvant-induced arthritis in rats and increases survival in a mouse model of septic shock. Increased plasma levels of α-MSH are positively correlated with delayed disease progression and reduced death in patients with HIV.1 1.Catania, A., Airaghi, L., Colombo, G., et al.α-melanocyte-stimulating hormone in normal human physiology and disease statesTrends Endocrinol. Metab.11(8)304-308(2000) 2.Miwa, H., Gantz, I., Konda, Y., et al.Structural determinants of the melanocortin peptides required for activation of melanocortin-3 and melanocortin-4 receptorsJ. Pharmacol. Exp. Ther.273(1)367-372(1995) 3.Cutuli, M., Cristiani, S., Lipton, J.M., et al.Antimicrobial effects of a-MSH peptidesJ. Leukoc. Biol.67(2)233-239(2000) 4.Lipton, J.M., Ceriani, G., Macaluso, A., et al.Antiiinflammatory effect of the neuropeptide a-MSH in acute, chronic, and systemic inflammationAnn. N.Y. Acad. Sci.25(741)137-148(1994)

α-Synuclein (61-95) (human) constitutes the hydrophobic core of α-synuclein and is implicated in inducing neuronal cell death. This segment is utilized in the study of neurodegenerative conditions such as Alzheimer's disease (AD) and Parkinson's disease (PD) [1] [2].

G* Peptide, also denoted as LVGRQLEEFL (mouse), represents the amino acid sequence 113 to 122 ([113,122] apoJ) found in apolipoprotein J. This compound displays both anti-inflammatory and anti-atherogenic characteristics. When incorporated into an apoJ mimetic, it results in the formation of the HM-10/10 peptide, which functions as a novel chimeric high-density lipoprotein. The HM-10/10 peptide has been shown to confer protection to the retinal pigment epithelium (RPE) and photoreceptors against oxidant-induced cell death [1] [2].

DAPK Substrate Peptide is a synthetic peptide substrate for death-associated protein kinase (DAPK) (Km = 9 μM).

Dynamin-related protein 1 (Drp1) inhibitor, inhibits Drp1 GTPase activity. Displays no effect on dynamin 1 or other mitochondrial dynamics-related proteins. Inhibits mitochondrial fission, dysfunction and reactive oxygen species (ROS) production in vitro.

WL12 is a peptide that targets and binds specifically to programmed death ligand 1 (PD-L1). It can be radiolabeled with various radionuclides to produce radiotracers, enabling the evaluation of PD-L1 expression in tumors [1].

α-Hemolysin (Staphylococcus aureus), a polypeptide virulence factor of Staphylococcus aureus, disrupts host cell plasma membranes. Upon binding to the cell surface, its monomers create a homoheptamic prepore, which evolves into a mature transmembrane pore, facilitating K+ and Ca2+ ion transport that induces necrotic death in target cells [1].

G* peptide, also known as LVGRQLEEFL (mouse) TFA, is a segment corresponding to amino acids 113 to 122 ([113,122] apoJ) of apolipoprotein J. This compound possesses both anti-inflammatory and anti-atherogenic qualities. When combined with an apoJ mimetic, it constitutes the HM-10/10 peptide, a novel chimeric high-density lipoprotein mimetic peptide. The HM-10/10 peptide is notable for safeguarding retinal pigment epithelium (RPE) and photoreceptors from oxidant-induced cell death as referenced in sources [1] [2].

Eciskafusp alfa, a cis-targeted IL2v immunocytokine, acts on programmed cell death 1 (PDCD1, commonly known as PD-1), preferentially targeting antigen-specific stem-like PD-1+ TCF-1+ CD8+ T cells to differentiate into a more effective effector population. This compound is applicable in the study of cancer and chronic infections [1].

CPM-1285 induces apoptosis by effectively inhibiting the function of intracellular Bcl-2 and associated death antagonists. It exhibits a high binding affinity for Bcl-2, with an IC50 of 130 nM, and has been demonstrated to decrease tumor burden in mice [1].

Cathepsin B, a cysteine protease, plays a role in various forms of programmed cell death, such as apoptosis, pyroptosis, ferroptosis, necroptosis, and autophagic cell death [1].

YVAD-CHO is an inhibitor of interleukin-1β converting enzyme (ICE, caspase 1) that has been shown to partially mitigate motoneuron death in mice with lesioned facial nerves [1].

Trofinetide, derived from the neuroprotective tripeptide Gly-Pro-Glu (an N-terminal sequence of insulin-like growth factor-1, IGF-1), shows promise in various neuroprotective models. At a concentration of 10 nM, it mitigates cell death in primary rat embryonic striatal neurons caused by okadaic acid. Additionally, Trofinetide reduces the expression of pro-inflammatory markers (IL-1β, TNF-α, IL-6, and E-selectin) in a rat model simulating neuroinflammation from penetrating ballistic-like brain injuries. In cases of brain injury induced by middle cerebral artery occlusion (MCAO), administration of Trofinetide at 30 and 60 mg/kg reduces the area of cortical and striatal infarct. Furthermore, a daily dose of 100 mg/kg reverses social recognition and contextual fear conditioning deficits, diminishes the number of dendritic spines, and decreases testicular weight gain in an fmr1-/- knockout mouse model of fragile X syndrome. Trofinetide formulations have been employed in treating Rett syndrome, highlighting its versatility across various neurological conditions.

Pinealon is a 3-amino acid peptide and shows neuroprotective properties. Pinealon prevents reactive oxygenspecies (ROS) accumulation and supressesthe activation of ERK 1/2. Pinealon has the ability to stimulate the functional activity of the main cellular elements of brain tissue, reduce the level of spontaneous cell death. Pinealon protects the rat offspring from prenatal hyperhomocysteinemia [1] [2] [3] .

TAT-BH4 (Bcl-xL) TFA, primarily localized at the mitochondria, inhibits apoptotic cell death. This compound comprises an eosin-labeled cysteine at the N-terminal and the protein transduction domain from the HIV TAT protein (amino acids 49 to 57), fused to the Bcl-xL BH4 peptide. It is utilized in research concerning diseases associated with accelerated apoptosis [1].

r8-Gly-Noxa A BH3 is a biologically active peptide with cell-permeability, comprising amino acid residues 17 to 36 derived from the BH3 (death) domain of Noxa A. The peptide is modified by the addition of eight D-Arginine residues and a Glycine linker at its amino terminal.

DAPK Substrate Peptide TFA is a synthetic peptide that serves as a substrate for the enzyme death-associated protein kinase (DAPK), exhibiting a Michaelis constant (Km) of 9 μM [1].

MDP1, derived from Melittin, disrupts the membrane integrity of both Gram-positive and Gram-negative bacteria, leading to bacterial death through membrane damage. This compound exhibits potent antibacterial activity against multidrug-resistant (MDR) and reference strains of S. aureus, E. coli, and P. aeruginosa [1].

Destruxin A is a cyclic hexadepsipeptide produced by fungus causing paralysis and death in insects.

Bid BH3 (80-99) is a biologically active peptide known as a pro-apoptotic member of the 'BH3-only' (BOPS) subset within the BCL-2 protein family, pivotal in apoptosis regulation. It notably interacts with Bcl-2, Bax, and Bak, initiating their activation or inactivation, thus inducing cell death. Additionally, Bid translocates from the cytosol to the mitochondrial membrane as part of its functional mechanism. The presence of Pyroglutamyl (pGlu) peptides, which can spontaneously arise from Glutamine (Q) or Glutamic acid (E) at the N-terminus of sequences, is a natural process. The hydrophobic γ-lactam ring of pGlu is theorized to enhance peptide stability, providing resistance to gastrointestinal proteases, making these peptides a recognized variant within peptide analyses, including HPLC purity assessments.

Bad BH3 (mouse) is a bioactive peptide derived from the BH3 domain (a death domain) of Bad, encompassing amino acid residues 140 to 165, and functions by binding to bcl-2.

TPP-1, a peptide inhibitor, targets the interaction between programmed cell death protein 1 (PD-1) and its ligand (PD-L1), binding specifically to PD-L1 with a dissociation constant (Kd) of 94.67 nM. At a concentration of 20 µM, TPP-1 effectively counteracts the PD-L1-induced suppression of IFN-γ production in anti-CD3-stimulated isolated human CD4+ T cells. Furthermore, TPP-1 demonstrates significant efficacy in reducing tumor volume in a mouse xenograft model of HL-60 leukemia. This model involved HL-60 cells co-cultured with anti-CD3-activated isolated human CD4+ T cells, with TPP-1 administration at a dosage of 4 mg/kg showing notable antitumor activity.

Connexin43 mimetic peptide. Reduces swelling, astrogliosis, neuroinflammation and neuronal cell death following spinal cord injury ex vivo and in vivo. Exhibits analgesic effects in models of neuropathic pain. O'Carroll et al (2008) Connexin 43 mimetic peptides reduce swelling, astrogliosis and neuronal cell death after spinal cord injury. Cell.Commun.Adhes. 15 27 PMID:18649176 |Mao et al (2017) Characterisation of Peptide5 systemic administration for treating traumatic spinal cord injured rats. Exp.Brain.Res. 235 3033 PMID:28725925 |Kim et al (2017) Characterising the mode of action of extracellular Connexin43 channel mimetic peptides in an in vitro ischemia injury model. Biochem.Biophys.Acta. 1861 68 PMID:27816754 |Tonkin et al (2017) Attenuation of mechanical pain hypersensitivity by treatment with Peptide5, a connexin-43 mimetic peptide, involves inhibition of NLRP3 inflammasome in nerve-injured mice. Exp.Neurol. 300 1 PMID:29055716

Dalargin, a potent δ-opioid receptor agonist, demonstrates efficacy in mitigating cell death induced by Gentamicin and exhibits nephroprotective effects against Gentamicin-induced kidney injury. Additionally, Dalargin possesses antiulcer activity [1] [2] [3].

MDP1 acetate, a derivative of Melittin, compromises the membrane integrity of both Gram-positive and Gram-negative bacteria leading to bacterial death through membrane damage. It exhibits potent antibacterial activity against multidrug-resistant (MDR) and reference strains of S. aureus, E. coli, and P. aeruginosa [1].

TAT-GluN2BCTM is a membrane-permeable peptide that selectively targets active DAPK1 (Death-associated protein kinase 1) for lysosomal degradation, thereby protecting neurons against oxidative stress and NMDAR-mediated excitotoxicity. This compound's role in facilitating neuroprotection makes it a valuable agent for related research studies [1].

TAT-BH4 (Bcl-xL), primarily localized at the mitochondria, inhibits apoptotic cell death. This compound comprises an N-terminal eosin-labeled cysteine and the protein transduction domain of the HIV TAT protein (amino acids 49 to 57), fused to the Bcl-xL BH4 peptide. It serves as a tool for research into diseases characterized by accelerated apoptosis [1].

Ac-Leu-Val-Lys-Aldehyde is a potent inhibitor of cathepsin B, exhibiting inhibitory concentration (IC50) values of 4 nM. It notably diminishes cell death in the striatum induced by quinolinic acid and leads to the accumulation of LC3-II [1].

Amylin (AMY3) receptor antagonist. Inhibits andrenomedulin-stimulated cAMP production in vitro. Protects against oligomeric Aβ-induced increase in intracellular Ca2+, activation of PKA, MAPK, Akt and cFOS and cell death in neuronal cell culture. Blocks el

Caspase-3 inhibitor. Inhibits MG 132-induced small cell lung cancer cell death in vitro.

BDS-I, a marine toxin derived from Anemonia sulcata, functions as a selective inhibitor of the potassium channel, specifically targeting Kv3.4. It impedes the Aβ1-42-induced augmentation of Kv3.4 activity, caspase-3 activation, and distortion of nuclear morphology in NGF-differentiated PC-12 cells. Moreover, BDS-I effectively counteracts the cell death induced by the Aβ peptide [1].

BMAP-28, an antibiotic peptide, induces cell death by triggering the mitochondrial permeability transition pore and serves as a research tool in the study of microbial infections and cancer [1].

Peptide5 TFA, a connexin 43 mimetic peptide, mitigates swelling, astrogliosis, and neuronal cell death in animal models of spinal cord injury. Additionally, it suppresses the NLRP3 inflammasome, functioning as an anti-inflammatory agent [1] [2] [3].

BRC4wt, an acetylated peptide originating from the BRC4 repeat within human BRCA2 (1521-1536), acts as an inhibitor of the BRCA2 and RAD51 protein-protein interaction. When linked to the cationic cell-penetrating peptide (Arg)9, it effectively shortens DNA replication tract lengths and diminishes the frequency of homologous repair of camptothecin-induced DNA damage in vitro. Additionally, BRC4wt enhances the efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib in inducing cell death in HeLa human cervical cancer and U2OS human osteosarcoma cells, albeit it does not affect non-cancerous hTERT RPE-1, MRC-5, or MCF-10A cells.

The compound 4A7C-301-Nurr1 agonist is a specific agonist for the nuclear receptor-related 1 (Nurr1). By binding to the Nurr1 ligand-binding domain with an IC50 value of 48.22 nM, it enhances the transcriptional activity of both Nurr1-LBD and the full-length Nurr1, as demonstrated in reporter assays using SK-N-BE(2)C human neuroblastoma cells, with EC50 values of 6.53 and 50-70 µM, respectively. Additionally, administration of 4A7C-301-Nurr1 agonist at a dosage of 5 mg/kg per day has been shown to mitigate dopaminergic cell death in the striatum and substantia nigra pars compacta and ameliorate motor and olfactory deficits in mouse models of Parkinson's disease, circumventing the induction of dyskinesia-like behaviors. These models were induced either by the neurotoxin MPTP or by overexpression of α-synuclein.

GPR, a tripeptide, shows promise in Alzheimer's disease (AD) research by protecting cultured rat hippocampal neurons from amyloid-beta (Aβ)-induced death through the inhibition of caspase-3/p53-dependent apoptosis.

Leptin (116-130), a bioactive fragment of leptin, enhances synaptic plasticity in the hippocampus by promoting AMPA receptor trafficking to synapses. It preserves hippocampal synapse integrity and prevents neuronal cell death in amyloid toxicity models, showing promise for Alzheimer's disease (AD) research [1].

Dynorphin A TFA, an endogenous opioid peptide, plays a role in inhibitory neurotransmission within the central nervous system (CNS). It acts as a highly potent kappa opioid receptor (KOR) agonist and also stimulates other opioid receptors, including mu (MOR) and delta (DOR). Furthermore, Dynorphin A TFA has been observed to induce neuronal death, making it a significant subject in neurological disease research [1] [2].

Calcineurin Autoinhibitory Peptide TFA is a selective inhibitor of Ca2+/calmodulin-dependent protein phosphatase (calcineurin), exhibiting an inhibitory concentration (IC50) of approximately 10 μM. This compound has been shown to protect neurons from excitatory neuronal death [1] [2].

Ozarelix is a fourth generation GnRH antagonist, induces apoptosis in hormone refractory androgen receptor negative prostate cancer cells modulating expression and activity of death receptors. Mechanistically, LHRH antagonists exert rapid inhibition of luteinizing hormone and follicle stimulating hormone with an accompanying rapid decrease in sex hormones and would therefore be expected to be effective in a variety of hormonally dependent disease states including ovarian cancer, prostate cancer, BPH, infertility, uterine myoma and endometriosis. BPH is a non-cancerous enlargement of the prostate that is caused by testosterone. Unlike LHRH agonists, ozarelix has the potential to reduce testosterone just enough to reduce both prostate size and symptoms without the severe side effects associated with a reduction in testosterone.