Triphenylamine is a fluorescent compound for photodynamic therapy research
**Background**
Photodynamic therapy (PDT) is a minimally invasive therapeutic approach that utilizes photosensitizers to generate reactive oxygen species upon light activation, leading to targeted cell death. This modality is particularly valuable in oncology for the precise destruction of malignant tissues while sparing surrounding healthy cells. The development of highly efficient fluorescent dyes that can induce apoptosis is critical for enhancing the efficacy and monitoring of these treatments. In the context of Triphenylamine Cancer research, the ability to combine high fluorescence with potent cytotoxic activity upon excitation makes certain aromatic amines ideal candidates for these applications. Therefore, we will introduce a highly fluorescent compound used in photodynamic therapy research – Triphenylamine.
**Definition**
Triphenylamine (N,N-Diphenylbenzenamine) is a highly fluorescent compound with the Triphenylamine formula $\text{C}_{18}\text{H}_{15}\text{N}$ and a molecular weight of 245.32.
**In Vitro Studies**
According to the Triphenylamine description, this compound serves as both a fluorescent dye and a potent inducer of apoptosis. Triphenylamine in vitro studies have demonstrated that triphenylamines can effectively induce cell death upon 2-photon excitation, highlighting their utility in high-resolution imaging and targeted therapy. Furthermore, research into the synthesis of bipolar compounds, such as the Triphenylamine/Diazafluorene-Carbazole derivative, has expanded the understanding of its photophysical properties, enhancing its application as a fluorescent probe. In conclusion, Triphenylamine is a highly fluorescent compound that induces apoptosis and serves as a valuable tool in photodynamic therapy research.
Keywords
Triphenylamine, 603-34-9, N,N-Diphenylbenzenamine, Apoptosis, Fluorescent Dye, Inhibitor, inhibitor, inhibit
References
[1] Sivakumar R, et al. Synthesis and Photophysical Properties of Bipolar Compound: Triphenylamine/Diazafluorene-Carbazole. J Fluoresc. 2025 Apr;35(4):2273-2284.
[2] Chennoufi R, et al. Triphenylamines Induce Cell Death Upon 2-Photon Excitation. Mol Imaging. 2017 Jan 1;16:1536012117714164.
**Background**
Matrix metalloproteinase-9 (MMP-9), also known as gelatinase B, is a zinc-dependent endopeptidase that plays a critical role in the degradation of extracellular matrix components. Overexpression and overactivation of MMP-9 are associated with various inflammatory conditions and tissue remodeling processes. In the context of the ocular surface, elevated levels of MMP-9 are frequently observed in patients with dry eye disease, where it contributes to corneal epithelial damage and chronic inflammation. Consequently, the development of highly selective MMP-9 inhibitors has become a significant research focus for treating ocular surface disorders. In this context, we will introduce a selective inhibitor of human MMP9 – MMP-9-IN-13.
**Definition**
MMP-9-IN-13 is a selective inhibitor of human MMP9 with an IC50 value of 0.02 nM.
**In Vitro Studies**
Regarding the MMP-9-IN-13 description, this compound is a derivative of 5-[2,7-diazaspiro[3.5]nonan-7-yl]-5-[4-phenoxyphenyl]hexahydropyrimidine-2,4,6-trione. The MMP-9-IN-13 formula is C26H27F3N4O6, with a molecular weight of 548.51. In terms of MMP-9-IN-13 biological activity, the compound demonstrates potent and selective inhibition of the MMP-9 enzyme, making it a valuable tool for investigating the molecular mechanisms of dry eye disease. By targeting the active site of MMP-9, it prevents the proteolytic degradation of the ocular surface matrix. In conclusion, MMP-9-IN-13 is a highly potent and selective MMP-9 inhibitor suitable for research on the treatment of dry eye disease and ocular surface inflammation.
Keywords
MMP-9-IN-13, 3085676-77-0, MMP, Matrix metalloproteinases, MMP9, ocular surface, Inhibitor, inhibitor, inhibit
References
**Background**
Cardiac arrhythmias, particularly atrial fibrillation, are characterized by abnormal electrical activity in the heart, often involving the dysfunction of ion channels. The regulation of action potential duration and refractoriness in the atria is heavily dependent on the activity of voltage-gated sodium (Na+) channels and potassium (K+) channels. Among these, the Kv1.5 channel plays a critical role in the ultra-rapid delayed rectifier potassium current, making it a primary target for pharmacological intervention to restore normal sinus rhythm. Developing agents that can selectively target atrial channels while minimizing effects on ventricular tissue is essential for safe and effective antiarrhythmic therapy. In this context, we will introduce a mixed voltage- and frequency-dependent channel blocker – Vernakalant.
**Definition**
Vernakalant hydrochloride is a mixed voltage- and frequency-dependent Na+ and atria-preferred K+ channel blocker. According to the Vernakalant description, it exhibits specific inhibitory activity against Kv1.5 channels with an IC50 value of 13.35±0.93 μM for the wild-type channel.
**In Vitro Studies**
The Vernakalant biological activity is characterized by its ability to block Kv1.5 channels in a manner mediated by channel activation. Specifically, Vernakalant causes a rapid onset of block upon depolarization, with little evidence of resting or “tonic” block. In Vernakalant in vitro experiments, the application of 10 μM Vernakalant results in a rapid block after channel opening, quickly reaching a steady-state current level. Further investigation into the molecular basis of its binding reveals that the potency is highly dependent on specific amino acid residues. For instance, the I502A mutation leads to a 25-fold decrease in potency, with the IC50 increasing to 329±19 μM compared to the control IC50 of 13.4±0.9 μM. Other mutations, such as V505A, I508A, T480A, and C500A, showed lesser reductions in potency, ranging between 3- and 4-fold. Additionally, the I508F and T479A mutant Kv1.5 channels exhibited fractional blocks of 0.61±0.03 μM and 1.63±0.09 μM, respectively. The I508Y mutation increased the IC50 to 24.7 μM. In conclusion, Vernakalant is a potent and selective blocker of atrial K+ channels, specifically targeting the Kv1.5 channel to modulate cardiac electrical activity.
Keywords
Vernakalant, 748810-28-8, RSD1235, RSD 1235, RSD-1235, Potassium Channel, KcsA, Inhibitor, inhibitor, inhibit
References
[1] Eldstrom J, et al. The molecular basis of high-affinity binding of the antiarrhythmic compound Vernakalant (RSD1235) to Kv1.5 channels. Mol Pharmacol. 2007 Dec;72(6):1522-34.
[2] Chiba T, et al. Influences of rapid pacing-induced electrical remodeling on pharmacological manipulation of the atrial refractoriness in rabbits. J Pharmacol Sci. 2016 Mar;130(3):170-6.
**Background**
Colon cancer remains one of the most prevalent and lethal malignancies worldwide, characterized by uncontrolled cell proliferation and resistance to apoptosis. A key driver in the progression of this disease is the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. NF-κB is a pivotal transcription factor that regulates genes involved in inflammation, cell survival, and immune responses; its constitutive activation is frequently observed in various tumors, promoting tumor growth and metastasis. Consequently, targeting the NF-κB pathway has become a significant strategy for developing novel anticancer therapies. In this context, we will introduce a flavonoid-based inhibitor used in Tectochrysin Cancer research – Tectochrysin.
**Definition**
Tectochrysin is a major flavonoid isolated from Alpinia oxyphylla Miquel that acts as an inhibitor of NF-κB activity. According to the Tectochrysin description, it specifically binds to the p50 unit of the NF-κB complex to exert its biological effects.
**In Vitro and In Vivo Studies**
The Tectochrysin biological activity has been extensively evaluated in various cancer models. Tectochrysin in vitro studies demonstrate that the compound inhibits the phosphorylation of IκB, thereby concentration-dependently blocking the translocation of p50 and p65 into the nucleus. In colon cancer cell lines, Tectochrysin inhibits the growth of SW480 and HCT116 cells with IC50 values of 6.3 μg/mL and 8.4 μg/mL, respectively, after 24 hours of treatment (1, 5, 10 μg/mL). Morphological analysis indicates a reduction in cell size, and DAPI and TUNEL staining confirm the induction of apoptotic cell death, with apoptotic cell numbers increasing to 58% in SW480 and 54% in HCT116 cells upon treatment with 10 μg/mL. Notably, Tectochrysin is not cytotoxic to normal CCD-18co cells at the tested concentrations.
Further Tectochrysin In Vivo evaluations were conducted using HCT116 xenograft-bearing nude mice. Tectochrysin (NSC 80687) was administered i.p. twice per week for 3 weeks at a dose of 5 mg/kg. The results showed that the final tumor weights and volumes in the treated group were reduced to 57.9% and 46.4% of the vehicle group, respectively, without significant changes in the body weight of the mice. In conclusion, Tectochrysin is a potent NF-κB inhibitor that suppresses colon cancer cell growth and tumor progression by inducing apoptosis.
Keywords
Tectochrysin, 520-28-5, Techtochrysin, NSC 80687, NSC80687, NSC-80687, STAT, NF-κB, Nuclear factor-κB, Nuclear factor-kappaB, Inhibitor, inhibitor, inhibit
References
**Background**
The histamine H3 receptor is a G protein-coupled receptor primarily located on presynaptic neurons, where it acts as an autoreceptor to inhibit the release of histamine and as a heteroreceptor to modulate the release of other neurotransmitters, including acetylcholine, dopamine, and norepinephrine. Due to its critical role in regulating wakefulness, cognition, and various neurological functions, the H3 receptor has become a significant target for the development of treatments for sleep disorders and cognitive impairments. Modulating this receptor through inverse agonism or antagonism can enhance histaminergic neurotransmission, thereby improving alertness and cognitive performance. In this context, we will introduce a potent and selective H3 receptor modulator – Pitolisant.
**Definition**
Pitolisant is a potent and selective nonimidazole inverse agonist at the recombinant human histamine H3 receptor with a $K_i$ value of 0.16 nM.
**In Vitro and In Vivo Studies**
According to the Pitolisant description, this compound acts as a competitive antagonist and inverse agonist. Pitolisant in vitro studies demonstrate that it behaves as a competitive antagonist with a $K_i$ of 0.16 nM and as an inverse agonist with an $EC_{50}$ value of 1.5 nM, exhibiting an intrinsic activity approximately 50% higher than that of ciproxifan. In mouse brain cortical membranes, it displaces $[^{125}I]$iodoproxyfan binding with an $IC_{50}$ of $26.4 \pm 4.5$ nM (deduced $K_i = 14 \pm 1$ nM). In membranes of rat glioma C6 cells stably expressing the human H3 receptor, it shows an $IC_{50}$ of $4.2 \pm 0.2$ nM (deduced $K_i = 2.7 \pm 0.5$ nM). Furthermore, it elicits a dose-dependent decrease of basal-specific $[^{35}S]GTP\gamma S$ binding with an $EC_{50}$ of $1.5 \pm 0.1$ nM. In CHO cells, it inhibits human ERG at a holding potential of -90 mV with an $IC_{50}$ of 1.7 $\mu$M.
Regarding Pitolisant In Vivo activity, administration of a single dose (10 mg/kg) 30 minutes before olanzapine (2 mg/kg) significantly affects immobility time and decreases locomotor activity in the forced swim test (FST) in mice. However, subchronic treatment (15 administrations) of Pitolisant (10 mg/kg) followed by olanzapine equalized locomotor activity and significantly reduced immobility time to control levels in the FST. Additionally, rats given Pitolisant (10 mg/kg) during the conditioning phase showed no significant difference in paired texture preference compared to controls, indicating a lack of place preference. For researchers seeking detailed Pitolisant technical information, these results highlight its complex neuromodulatory effects. In conclusion, Pitolisant is a highly selective nonimidazole inverse agonist of the histamine H3 receptor with significant potential for neurological research.
Keywords
Pitolisant, 362665-56-3, Tiprolisant, Histamine Receptor, Inhibitor, inhibitor, inhibit
References
[1] Ligneau X, et al. BF2.649 [1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride], a nonimidazole inverse agonist/antagonist at the human histamine H3 receptor: Preclinical pharmacology. J Pharmacol Exp Ther. 2007 Jan;320(1):365-75.
[2] Dudek M, et al. H3 histamine receptor antagonist pitolisant reverses some subchronic disturbances induced by olanzapine in mice. Metab Brain Dis. 2016 Oct;31(5):1023-9.
[3] Uguen M, et al. Preclinical evaluation of the abuse potential of Pitolisant, a histamine H? receptor inverse agonist/antagonist compared with Modafinil. Br J Pharmacol. 2013 Jun;169(3):632-44.
**Background**
Neurological disorders, including traumatic brain injury (TBI), Niemann-Pick disease type C, and various neurodegenerative conditions, are characterized by neuronal death, neuroinflammation, and metabolic dysfunction. These conditions often lead to severe functional impairments, such as postural imbalance and cognitive decline, necessitating the development of brain-penetrant therapeutic agents. Addressing lysosomal dysfunction and preventing cortical cell death are critical strategies for improving functional recovery in patients with brain injuries and genetic neurodegenerative diseases. In this context, we will introduce a promising acetylated amino acid derivative – N-Acetyl-L-leucine.
**Definition**
N-Acetyl-L-leucine (also known as Levacetylleucine) is an orally bioavailable and brain-penetrant compound that serves as the active form of N-acetyl-leucine (NAL). According to the N-Acetyl-L-leucine description, it is an acetylated derivative of the amino acid Leucine.
**In Vivo Studies**
The N-Acetyl-L-leucine biological activity has been demonstrated across several animal models of neurological impairment. In rats subjected to unilateral chemical labyrinthectomy (UL), administration of N-Acetyl-L-leucine (60 mg/kg; i.v.; days 1, 2, and 3 for 15 days) significantly decreased postural imbalance scores on day 7 and accelerated the course of postural compensation by approximately 6 days. Furthermore, in C57/BL6 mice, oral gavage of the compound (100 mg/kg; daily for 1-28 days) did not affect body weight or food intake. Specifically, in the N-Acetyl-L-leucine in vivo model of traumatic brain injury, daily oral administration (100 mg/kg; 28 days) attenuated cortical cell death and neuroinflammation, preventing the peak of cell death typically observed at early time points (day 1) after TBI. Additionally, the compound potentially ameliorates lysosomal and metabolic dysfunction, making it a valuable tool for researching Niemann-Pick disease type C. In conclusion, N-Acetyl-L-leucine is a neuroprotective agent that attenuates neuronal death and neuroinflammation, offering significant potential for the treatment of traumatic brain injury and neurodegeneration.
Keywords
Levacetylleucine, 1188-21-2, N-Acetyl-L-leucine, Amino Acid Derivatives, orally bioavailable, acetylated derivative, neuronal death and neuroinflammation, lysosomal and metabolic dysfunction, Niemann-Pick disease type C, traumatic brain injury, neurodegeneration prevention, Inhibitor, inhibitor, inhibit
References
[1] Bremova-Ertl T, et al. Trial of N-Acetyl-l-Leucine in Niemann-Pick Disease Type C[J]. N Engl J Med. 2024 Feb 1;390(5):421-431.
[2] Sarkar C, et al. N-acetyl-L-leucine: a promising treatment option for traumatic brain injury[J]. Neural Regen Res. 2022 Sep;17(9):1957-1958.
[3] Günther L, et al. N-acetyl-L-leucine accelerates vestibular compensation after unilateral labyrinthectomy by action in the cerebellum and thalamus[J]. PLoS One. 2015 Mar 24;10(3):e0120891.
[4] Hegdekar N, et al. N-Acetyl-L-leucine improves functional recovery and attenuates cortical cell death and neuroinflammation after traumatic brain injury in mice[J]. Sci Rep. 2021 Apr 29;11(1):9249.
**Background**
Histamine H1 receptors play a critical role in mediating allergic reactions, inflammatory responses, and various physiological processes in the central nervous system. Antagonists of these receptors are widely utilized to manage allergic symptoms and motion sickness. Beyond its antihistamine properties, research has indicated that certain H1-receptor antagonists possess anti-cholinergic effects and can modulate ion channels, including the N-methyl-D-aspartate (NMDA) receptor. The ability of these compounds to cross the blood-brain barrier makes them valuable tools for studying sedative, analgesic, and memory-related effects. Furthermore, emerging evidence suggests that these agents may offer protective benefits against drug-induced organ toxicity. In this context, we will introduce a first-generation histamine H1-receptor antagonist – Diphenhydramine.
**Definition**
Diphenhydramine is a first-generation histamine H1-receptor antagonist with anti-cholinergic effects and an IC50 value of 24.6 μM against the GluN1/GluN2B NMDA receptor.
**In Vitro and In Vivo Studies**
According to the Diphenhydramine description, this compound acts as an open channel blocker of NMDA receptors. Diphenhydramine in vitro studies using human TsA cells demonstrated that concentrations of 1-300 μM (30 s incubation) can block NMDA-activated membrane currents. Specifically, the IC50 against GluN1/GluN2B was 24.6 μM, while the IC50 against GluN1/GluN2A was 24.4 μM. Additionally, whole-cell patch clamp experiments in HEK-293 cells showed that Diphenhydramine inhibits sodium currents (IC50 = 41,000 nM) and inhibits TEA uptake in OCT1-expressing (IC50 = 24 μM) and OCT2-expressing (IC50 = 32 μM) MDCK cells. In guinea pig ventricular myocytes, it inhibits L-type calcium channels with an IC50 of 228 μM.
Regarding Diphenhydramine In Vivo activity, administration of 20 mg/kg (i.p.) in mice was found to improve kidney injury induced by Cisplatin (CDDP) without compromising the anti-tumor efficacy of the chemotherapy. Pharmacokinetic studies in healthy dogs (5 mg/kg) indicated that oral absorption and half-life are significantly improved when administered as the combination product Dimenhydrinate. For researchers seeking detailed Diphenhydramine technical information, these results highlight its versatility as both a neurological modulator and a protective agent against nephrotoxicity. In conclusion, Diphenhydramine is a multi-target antagonist that inhibits H1 and NMDA receptors, providing significant utility in pharmacological and toxicological research.
Keywords
Diphenhydramine, 58-73-1, Histamine Receptor, Bacterial, Endogenous Metabolite, iGluR, Ionotropic glutamate receptors, allergy, hay fever, common cold, Cisplatin, 3LL cells, MKN45 cells, colon26 cells, HeLa cells, Inhibitor, inhibitor, inhibit
References
[1] Jason P Berninger, et al. Effects of the antihistamine diphenhydramine on selected aquatic organisms. Environ Toxicol Chem. 2011 Sep;30(9):2065-72.
[2] Föhr KJ, et al. Open channel block of NMDA receptors by diphenhydramine. Neuropharmacology. 2015 Dec;99:459-70.
[3] Ehling S, et al. Diphenhydramine pharmacokinetics after oral and intravenous administration of diphenhydramine and oral administration of dimenhydrinate to healthy dogs, and pharmacodynamic effect on histamine-induced wheal formation: a pilot study. Vet Dermatol. 2019 Apr;30(2):91-e24.
[4] Hamano H, et al. Diphenhydramine may be a preventive medicine against cisplatin-induced kidney toxicity. Kidney Int. 2021 Apr;99(4):885-899.
**Background**
The study of drug metabolism and gastrointestinal motility is essential for understanding how the body processes pharmacological agents and manages digestive functions. In particular, the cytochrome P450 (CYP) enzyme system plays a critical role in the oxidative metabolism of a vast array of xenobiotics in the liver. Identifying specific CYP enzymes responsible for the metabolism of certain compounds allows researchers to probe hepatic function and drug-drug interactions. Additionally, the regulation of gastric emptying is a key physiological process influenced by the central nervous system and the vagus nerve. Understanding the factors that delay gastric emptying is vital for developing treatments for gastrointestinal disorders. In this context, we will introduce an orally active antipyretic and analgesic agent used as a metabolic probe – Antipyrine.
**Definition**
Antipyrine (Phenazone) is an orally active antipyretic and analgesic compound with the molecular formula C11H12N2O. It serves as a probe agent for oxidative agent metabolism and is used to study gastric retention.
**In Vitro and In Vivo Studies**
The Antipyrine description highlights its utility in both biochemical and physiological research. Regarding Antipyrine in vitro activity, studies using human liver microsomes demonstrated that metabolites are formed by at least six hepatic cytochrome P450 enzymes, including CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C18, and CYP3A4, when treated with concentrations of 0.1-100 mM for 15 minutes. These findings provide critical Antipyrine technical information for researchers utilizing the compound as a probe for human oxidative drug metabolism.
In terms of Antipyrine In Vivo application, the compound has been shown to influence gastrointestinal motility. In Wistar rats, the administration of Antipyrine at a dose of 45.17 mg/kg via intravenous (i.v.) injection, 10 minutes prior to the evaluation of gastric retention, significantly delayed the gastric emptying (GE) of liquids. This effect is mediated by the participation of the vagus nerve and can be blocked through the activation of GABA B receptors in the central nervous system, resulting in a significantly more elevated percentage of gastric retention (%GR). In conclusion, Antipyrine is a versatile pharmacological tool used as an analgesic, an antipyretic, and a probe for studying hepatic metabolism and gastric motility.
Keywords
Antipyrine, 60-80-0, Phenazone, Phenazon, Fluorescent Dye, GABA Receptor, Gamma-aminobutyric acid Receptor, γ-Aminobutyric acid Receptor, antipyretic, analgesic, probe, oxidative, Inhibitor, inhibitor, inhibit
References
[1] Stevenson, I.H., Factors influencing antipyrine elimination. Br J Clin Pharmacol, 1977. 4(3): p. 261-5.
[2] Engel G, et, al. Antipyrine as a probe for human oxidative drug metabolism: identification of the cytochrome P450 enzymes catalyzing 4-hydroxyantipyrine, 3-hydroxymethylantipyrine, and norantipyrine formation. Clin Pharmacol Ther. 1996 Jun;59(6):613-23.
[3] RENKIN EM. Capillary and cellular permeability to some compounds related to antipyrine. Am J Physiol. 1953 Apr;173(1):125-30.
[4] Soares AC, et al. Effect of antipyrine on the gastric emptying of liquid in rats. Braz J Med Biol Res. 2006 Nov;39(11):1507-12.
**Background**
Radiation therapy and chemotherapy are cornerstones of cancer treatment; however, their clinical utility is often limited by the collateral damage they inflict on normal, healthy tissues. The generation of oxygen-derived free radicals during these treatments leads to oxidative stress, resulting in severe side effects and systemic toxicity. To mitigate these risks, researchers have focused on developing selective cytoprotective agents that can shield normal cells without compromising the efficacy of the antitumor treatment. In the context of Amifostine Cancer research, identifying molecules that can induce protective cellular responses, such as the activation of hypoxia-inducible factor-α1 (HIF-α1) and p53, is critical for improving patient outcomes. Therefore, we will introduce a broad-spectrum cytoprotective agent and radioprotector – Amifostine.
**Definition**
Amifostine trihydrate (WR2721 trihydrate) is a broad-spectrum cytoprotective agent and radioprotector that selectively protects normal tissues from damage caused by radiation and chemotherapy.
**In Vitro and In Vivo Studies**
According to the Amifostine description, this compound acts as a potent inducer of p53 and HIF-α1, while protecting cells by scavenging oxygen-derived free radicals. It further exhibits antiangiogenic properties and reduces renal toxicity. Regarding Amifostine in vitro activity, studies demonstrated that Amifostine (0.78125-100 μM; 24 h) reduces tert-Butyl hydroperoxide (TBHP)-induced cell damage in a dose-dependent manner, significantly reducing apoptosis in H9c2 cells at a concentration of 100 μM.
Amifostine in vivo studies have highlighted its potential in treating ischemia/reperfusion (I/R) injury. In male C57BL/6 mice with myocardial I/R injury, the administration of Amifostine (400 mg/kg; i.v.; 4 h) provided a significant protective effect. This treatment attenuated cardiomyocyte apoptosis and reduced the production of I/R-induced reactive oxygen species (ROS). Specifically, it significantly reduced the expression of Bax and cleaved caspase 3 while enhancing the expression of Bcl2, SOD1, and SOD2. Furthermore, it increased SOD activity and reduced MDA levels. In conclusion, Amifostine is a potent cytoprotective agent that attenuates oxidative stress and apoptosis across various tissue models.
Keywords
Amifostine, 112901-68-5, WR2721, WR 2721, WR-2721, MDM-2/p53, HIF/HIF Prolyl-Hydroxylase, Hypoxia-inducible factors, HIFs, HIF-PH, Broad-spectrum, radioprotector, cytoprotective, thiol, antiangiogenic
References
[1] D Maurici, et al. Amifostine (WR2721) restores transcriptional activity of specific p53 mutant proteins in a yeast functional assay. Oncogene. 2001 Jun 14;20(27):3533-40.
[2] Efstathia Giannopoulou, et al. Amifostine inhibits angiogenesis in vivo. J Pharmacol Exp Ther. 2003 Feb;304(2):729-37.
[3] Michael I Koukourakis, et al. Amifostine induces anaerobic metabolism and hypoxia-inducible factor 1 alpha. Cancer Chemother Pharmacol. 2004 Jan;53(1):8-14.
[4] John R Kouvaris, et al. Amifostine: the first selective-target and broad-spectrum radioprotector. Oncologist. 2007 Jun;12(6):738-47.
[5] Shao-Ze Wu, et al. Amifostine Pretreatment Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Apoptosis and Oxidative Stress. Oxid Med Cell Longev. 2017;2017:4130824.
**Background**
The BAF (SWI/SNF) complex is a multi-subunit nucleosome remodeling complex that plays a critical role in regulating chromatin structure and gene expression. Dysregulation of BAF complex subunits is frequently observed in various malignancies, making them attractive targets for therapeutic intervention. Specifically, the BAF ATPase subunits, such as SMARCA2 and SMARCA4, are essential for the complex’s remodeling activity and are often implicated in cancer progression. Proteolysis-targeting chimeras (PROTACs) have emerged as a powerful strategy to address these targets by recruiting an E3 ubiquitin ligase to a target protein, leading to its selective ubiquitination and subsequent proteasomal degradation. Given the importance of these subunits in SMARCA-BD ligand 1 for PROTAC Cancer research, developing high-affinity ligands for these proteins is crucial. In this context, we will introduce a specialized ligand used for the degradation of SMARCA2 – SMARCA-BD ligand 1 for PROTAC.
**Definition**
SMARCA-BD ligand 1 for PROTAC is a small molecule ligand (hydrochloride salt) designed to bind to the BAF ATPase subunits SMARCA2, SMARCA4, and PBRM1. It serves as the target-binding moiety in the construction of PROTACs aimed at the selective degradation of SMARCA2.
**In Vitro Studies**
According to the SMARCA-BD ligand 1 for PROTAC description, this compound possesses a molecular weight of 307.78 and a chemical formula of C14H18ClN5O. In terms of SMARCA-BD ligand 1 for PROTAC biological activity, the compound is utilized as a building block for PROTACs, which consist of two distinct ligands connected by a linker: one ligand for an E3 ubiquitin ligase and another for the target protein. By exploiting the intracellular ubiquitin-proteasome system, these chimeric molecules can selectively degrade target proteins. In vitro applications demonstrate that ligands targeting the SMARCA-BD ligand 1 for PROTAC epigenetic reader domain can be leveraged to create degraders that effectively reduce the protein levels of SMARCA2. This structure-based design allows for the exploitation of BAF complex vulnerabilities in cancer cells. In conclusion, SMARCA-BD ligand 1 for PROTAC is a potent ligand used for the development of PROTACs to achieve the selective degradation of SMARCA2.
Keywords
SMARCA-BD ligand 1 for PROTAC, 2380272-56-8, Ligands for Target Protein for PROTAC, SWI/SNF Complex, Target Protein-binding Moiety, SWI/SNF Family of Chromatin-Remodelling Complexes, Inhibitor, inhibitor, inhibit
References