senescent

BRD4770, a histone methyltransferase G9a inhibitor, induces cell senescence.

BRD9539 is an inhibitor of euchromatin histone methyltransferase 2 (EHMT2), also known as G9a, with an IC50 value of 6.3 μM

GLF16 HCl (GLF16) belongs to fluorescent dyes and is a fluorescent Sudan Black B analog, serving as a non-targeted probe. This compound possesses good cell permeability and is suitable for live cells and in vivo environments. The probe enables rapid detection, isolation, and real-time tracking of senescent cells via fluorescence microscopy and flow cytometry.

SSK1 is a compound that selectively kills senescent cells and is a precursor for β-galactosidase, which can reduce the inflammatory response of the body. SSK1 can activate the phosphorylation of p38 MAPK and MKK3/MKK6 in senescent cells, and promote mitochondrial DNA damage in senescent cells.

BRD-K56819078, a Bcl-2 inhibitor, significantly reduces the burden of senescent cells and the mRNA expression of aging-related genes in the kidneys. It exerts its anti-aging effects by inhibiting cell apoptosis (apoptosis).

BRD-K20733377 is a Bcl-2 inhibitor that exhibits selective cytotoxicity toward senescent cells, specifically inhibiting the activity of etoposide-induced senescent IMR-90 cells with an IC50 of 10.7 μM. Additionally, BRD-K20733377 reduces the mRNA expression of aging-related genes p16, p21, and KI67 in aged mouse models.

GL392 is a senolytic agent that delivers the potent senescence-clearing compound Dasatinib specifically to senescent cells. By targeting the LBD domain, it binds lipofuscin in these cells and releases Dasatinib via an ester linkage, inducing apoptosis (Apoptosis) in senescent cells. Additionally, GL392 is encapsulated in PEO-b-PCL microcapsules to ensure efficient intracellular delivery while minimizing systemic toxicity. GL392 is applicable in cancer research.

Dasatinib derivative 1 (2e) effectively releases nitric oxide (NO) and increases the concentration of 3’,5’-cyclic guanosine monophosphate (cGMP), while maintaining senescent cell-clearing activity. This compound can be utilized for research into chronic ocular hypertension (COHT) glaucoma.

JX10 is an anti-aging agent. It suppresses the expression of p38 MAPK and NF-κB. JX10 demonstrates significant anti-aging effects in C. elegans, senescent cells, and aged mice.

Gal-ARV-771 is a PROTAC prodrug, modified with galactose, based on ARV-771. It is activated in senescent cancer cells that express SA-β-Gal, thereby releasing ARV-771. Through the ubiquitin-proteasome pathway, Gal-ARV-771 induces selective degradation of the BRD4 protein in senescent cells and promotes apoptosis (apoptosis) of these cancer cells.

MS99-β-Gal (Gal-MS99) is a galactose-modified NPM-ALK PROTAC degrader. It is selectively hydrolyzed by SA-β-galactosidase (SA-β-gal) and esterases specifically in senescent cancer cells, releasing MS99, which targets the degradation of the NPM-ALK fusion protein. In senescent Karpas 299 cells, MS99-β-Gal has an IC50 value of 454.8 nM, significantly lower than its IC50 of 2.162 μM in normal Karpas 299 cells. This compound is applicable in cancer research.

Epitalon is a synthetic tetrapeptide with anti-aging properties.1,2,3,4 Dietary administration of epitalon (0.00001% w/w) reduces levels of lipid peroxidation products in aged D. melanogaster tissue homogenates.1 Epitalon (1 μg/animal) delays age-related estrous shutdown and decreases the frequency of bone marrow cell chromosomal aberrations in female mice.2 It decreases spontaneous mammary gland and ovarian tumor development and metastasis in aged female mice.3 Epitalon also stimulates melatonin synthesis and normalizes the circadian rhythm of cortisol secretion in senescent female M. mulatta monkeys.4References1. Khavinson, V.K., and Myl'nikov, S.V. Effect of epithalone on the age-specific changes in the time course of lipid peroxidation in Drosophila melanogaster. Bull. Exp. Biol. Med. 130(11), 1116-1119 (2000).2. Anisimov, V.N., Khavinson, V.K., Popovich, I.G., et al. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology 4(4), 193-202 (2003).3. Kossoy, G., Anisimov, V.N., Ben-Hur, H., et al. Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H/He mice. In Vivo 20(2), 253-257 (2006).4. Khavinson, V., Goncharova, N., and Lapin, B. Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in senescent monkeys. Neuro. Endocrinol. Lett. 22(4), 251-254 (2001). Epitalon is a synthetic tetrapeptide with anti-aging properties.1,2,3,4 Dietary administration of epitalon (0.00001% w/w) reduces levels of lipid peroxidation products in aged D. melanogaster tissue homogenates.1 Epitalon (1 μg/animal) delays age-related estrous shutdown and decreases the frequency of bone marrow cell chromosomal aberrations in female mice.2 It decreases spontaneous mammary gland and ovarian tumor development and metastasis in aged female mice.3 Epitalon also stimulates melatonin synthesis and normalizes the circadian rhythm of cortisol secretion in senescent female M. mulatta monkeys.4 References1. Khavinson, V.K., and Myl'nikov, S.V. Effect of epithalone on the age-specific changes in the time course of lipid peroxidation in Drosophila melanogaster. Bull. Exp. Biol. Med. 130(11), 1116-1119 (2000).2. Anisimov, V.N., Khavinson, V.K., Popovich, I.G., et al. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology 4(4), 193-202 (2003).3. Kossoy, G., Anisimov, V.N., Ben-Hur, H., et al. Effect of the synthetic pineal peptide epitalon on spontaneous carcinogenesis in female C3H/He mice. In Vivo 20(2), 253-257 (2006).4. Khavinson, V., Goncharova, N., and Lapin, B. Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in senescent monkeys. Neuro. Endocrinol. Lett. 22(4), 251-254 (2001).

BM-1244 is a potent Bcl-xL/Bcl-2 inhibitor with Kis of 134 and 450 nM for Bcl- xL and Bcl-2, respectively. BM-1244 inhibits senescent fibroblasts (SnCs) with an EC50 of 5 nM[1].

Resolvin E4 (RvE4) is a member of the specialized pro-resolving mediator (SPM) family of bioactive lipids.1It is produced from eicosapentaenoic acid by 15-lipoxygenase (15-LO)via15(S)-HpEPE and 15S-hydroxy, 5S-HpEPE intermediatesin vitroand by isolated human M2 macrophages or polymorphonuclear (PMN) neutrophils under normoxic or hypoxic conditions. RvE4 synthesis is enhanced in M2 macrophage and neutrophil co-cultures, indicating transcellular biosynthesis by a potential 15-LO and 5-LO mechanism. It has been found in mouse inflammatory exudates. RvE4 (10 nM) increases efferocytosis of apoptotic neutrophils or senescent red blood cells (sRBCs) by human M2 macrophages under hypoxic conditionsin vitro. Intraperitoneal administration of RvE4 (100 ng/animal) inhibits increases in inflammatory exudate neutrophil infiltration in a mouse model of hemorrhagic peritonitis induced by zymosan A and thrombin. It also increases inflammatory exudate macrophage infiltration and efferocytosis of apoptotic neutrophils and/or RBCs in the same model. 1.Norris, P.C., Libreros, S., and Serhan, C.N.Resolution metabolomes activated by hypoxic environmentSci. Adv.5(10)eaax4895(2019)

UBX1325, a Bcl-xL inhibitor, enhances apoptosis in senescent cells, serving as an effective anti-aging agent. It holds potential for age-related eye disease research, including diabetic macular oedema (DME), age-related macular degeneration (AMD), and diabetic retinopathy (DR) [1].

FOXO4-DRI, a cell-permeable peptide antagonist, inhibits the interaction between FOXO4 and p53. It functions as a senolytic peptide, promoting apoptosis in senescent cells [1].

Anti-aging agent 1 (compound 24), a piperlongumine (PL) derivative, demonstrates a significant enhancement in senolytic activity, being 50 times more effective against senescent WI-38 fibroblasts than PL [1].

E16-uPA24 is a chimeric peptide that targets the urokinase-type plasminogen activator receptor (uPAR). It uses polyglutamic acid to modify the surface of senescent cells, promoting an immune response through glutamic acid recognition. This compound enhances immune cell recruitment and directly links senescent and immune cells, leading to the immune clearance of senescent cells and the restoration of tissue homeostasis. E16-uPA24 is applicable in research on tissue degeneration, chronic inflammatory diseases, and age-associated tumorigenesis.