A 779 is a Mas receptor antagonist for bone health and vascular research
**Background**
The renin-angiotensin system (RAS) is a complex hormonal cascade critical for regulating blood pressure, fluid balance, and various inflammatory responses. While the classical AngII/AT1R axis is primarily associated with vasoconstriction and inflammation, the alternative ACE2/Ang-(1-7)/Mas receptor axis generally exerts counter-regulatory, protective effects. The Mas receptor, a G-protein coupled receptor, mediates the beneficial actions of Ang-(1-7), including anti-inflammatory and osteo-protective properties. Understanding the specific role of this axis is essential for developing therapies for cardiovascular diseases and metabolic bone disorders, such as osteoporosis. In this context, we will introduce a specific antagonist of the Mas receptor – A 779.
**Definition**
A 779 is a specific antagonist of the G-protein coupled Mas receptor, which is the primary receptor for Ang-(1-7). According to the A 779 description, it is a peptide-based compound with the molecular formula C39H60N12O11.
**In Vitro and In Vivo Studies**
The A 779 biological activity has been extensively evaluated in both cellular and animal models. In vitro studies demonstrate that A 779 inhibits the effects of Ang-(1-7), specifically blocking its ability to suppress the proliferating cell nuclear antigen (PCNA) protein expression that is up-regulated by Ang II. Furthermore, A 779 blocks the ability of Ang-(1-7) to retard Ang II-induced inflammatory responses in vascular smooth muscle cells (VSMCs), which are characterized by the up-regulation of MCP-1, VCAM-1, and IL-1β. Additionally, A 779 inhibits the Ang-(1-7)-mediated suppression of Akt and ERK1/2 phosphorylation induced by Ang II. Notably, A 779 alone does not induce proliferation, migration, or inflammatory responses in VSMCs.
In vivo research highlights the importance of the Mas receptor in bone metabolism. In ovariectomized (OVX) rats, A 779 in vivo administration (400 ng/kg/min, s.c.) for 6 weeks markedly elevated serum bone-specific alkaline phosphatase (BALP), telopeptides of collagen type I (CTX), tartarate-resistant acid phosphatase (TRAcP 5b), and osteocalcin (OC), as well as urinary deoxypyridinoline (DPD). By blocking the Mas receptor, A 779 abolished the favorable effects of Ang-(1-7) on bone health and eradicated the protective effects of captopril on bone mineralization and microstructure. It was further observed that A 779 restored OVX-induced effects on RANKL expression and the ACE-1/AngII/AT1R cascade while down-regulating the ACE-2/Ang1-7/Mas pathway. In conclusion, A 779 is a potent Mas receptor antagonist that serves as a critical tool for studying the ACE2/Ang-(1-7)/Mas axis in vascular and bone research.
Keywords
A 779, 159432-28-7, A779, A-779, Angiotensin Receptor, Inhibitor, inhibitor, inhibit
References
[1] Abuohashish HM, et al. Angiotensin (1-7) ameliorates the structural and biochemical alterations of ovariectomy-induced osteoporosis in rats via activation of ACE-2/Mas receptor axis. Sci Rep. 2017 May 23;7(1):2293.
[2] Abuohashish HM, et al. ACE-2/Ang1-7/Mas cascade mediates ACE inhibitor, captopril, protective effects in estrogen-deficient osteoporotic rats. Biomed Pharmacother. 2017 Aug;92:58-68.
[3] Yan WF, et al. Effects and related mechanism of angiotensin-(1-7) on Toll-like receptor 4-mediated oxidative stress in human umbilical vein endothelial cells. Zhonghua Xin Xue Guan Bing Za Zhi. 2017 Mar 24;45(3):223-229.
**Background**
Neutral endopeptidase (NEP) and aminopeptidase N (APN) are membrane-bound enzymes that play critical roles in the degradation of various endogenous opioid peptides. The dysregulation of these enzymes is often linked to the progression of several pathologies, including chronic pain, inflammatory bowel disease, and various malignancies. By inhibiting these peptidases, it is possible to maintain the levels of endogenous opioids, which can modulate pain responses and inhibit abnormal cell proliferation. In particular, the regulation of the ERK/mTOR signaling pathway has emerged as a key mechanism for controlling the growth of colorectal cancer, glioma, and prostate cancer cells. In this context, we will introduce a potent NEP and APN inhibitor – Sialorphin.
**Definition**
Sialorphin is a neutral endopeptidase (NEP) and aminopeptidase N (APN) inhibitor that interacts with $\mu$-, $\delta$-, and $\kappa$-opioid receptors. According to the Sialorphin description, it serves as a copper (II) ion-binding ligand and exhibits an $\text{IC}_{50}$ of $3.9 \times 10^{-7}\text{ M}$ for inhibiting $^3\text{H-SP}$ degradation.
**In Vitro and In Vivo Studies**
The Sialorphin biological activity is characterized by its ability to block the degradation of endogenous opioid peptides and regulate the ERK/mTOR pathway. Sialorphin in vitro studies using rat spinal cord slice cells demonstrated that concentrations of $4\text{–}10\text{ }\mu\text{M}$ for 20 minutes effectively prevented the breakdown of exogenous Met-enkephalin (ME) with an inhibition rate of 70% to 96%. Furthermore, it inhibited the endoproteolysis of $^3\text{H-SP}$ in rat renal cell membranes with an $\text{IC}_{50}$ of $1\text{ }\mu\text{M}$, showing competitive inhibition comparable to phosphoramidon. Regarding Sialorphin Cancer research, the compound induces cell cycle arrest and reduces the phosphorylation levels of mTOR, 4E-BP1, and p70S6K, thereby exhibiting antiproliferative activity against glioma, prostate, and colorectal cancer cells without cytotoxicity.
Sialorphin In Vivo evaluations focused on inflammatory bowel disease using BALB/c mice. In acute TNBS-induced colitis models, doses of 0.3, 1, and $3\text{ mg/kg}$ (i.p.; twice daily for 3 days) significantly attenuated macroscopic damage, ulceration, and MPO activity. In chronic relapsing TNBS-induced colitis, $1\text{ mg/kg}$ (i.p.; twice daily for 7 days) reduced clinical and histological markers of inflammation, including the expression of pro-inflammatory cytokines $\text{TNF}\alpha$ and $\text{IL-1}\beta$. However, it did not exhibit anti-inflammatory activity in DSS-induced colitis models. In conclusion, Sialorphin is a multifunctional NEP/APN inhibitor with significant potential in pain management, oncology, and the treatment of inflammatory bowel disease.
Keywords
Sialorphin, Enteropeptidase, Aminopeptidase, Opioid Receptor, ERK, mTOR, Androgen Receptor, Enterokinase, Transmembrane serine protease 15, TMPRSS15, Extracellular signal regulated kinases, Mammalian target of Rapamycin, copper(II) ion, δ-opioid receptors, glioma cancer cells
References
[1] Rougeot C, et al. Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity. Proc Natl Acad Sci U S A. 2003;100(14):8549-8554.
[2] Salaga M, et al. Systemic Administration of Sialorphin Attenuates Experimental Colitis in Mice via Interaction With Mu and Kappa Opioid Receptors. J Crohns Colitis. 2017;11(8):988-998.
[3] Mizerska-Kowalska M, et al. Neutral endopeptidase (NEP) inhibitors–thiorphan, sialorphin, and its derivatives exert anti-proliferative activity towards colorectal cancer cells in vitro[J]. Chemico-Biological Interactions, 2019, 307: 105-115.
[4] Kamysz E, et al. Antitumor activity of opiorphin, sialorphin and their conjugates with a peptide klaklakklaklak. J Pept Sci. 2016;22(11-12):723-730.
[5] Kamysz E, et al. Sialorphin and its analog as ligands for copper (II) ions[J]. Polyhedron, 2013, 55: 216-224.
**Background**
Olanzapine is a widely utilized atypical antipsychotic medication primarily prescribed for the treatment of schizophrenia and bipolar disorder. The pharmacological efficacy and safety profile of olanzapine are heavily influenced by its metabolic pathways and stability. Understanding the metabolites and degradation products of this compound is critical for pharmacokinetic studies, drug safety assessments, and forensic toxicology. Specifically, the identification of metabolites allows researchers to determine how the drug is processed in the body and how it may break down under various environmental conditions. In this context, we will introduce a key metabolite and degradation product – 2-Hydroxymethyl olanzapine.
**Definition**
2-Hydroxymethyl olanzapine is a metabolite and a degradation product of olanzapine, characterized by the molecular formula C17H20N4OS and a molecular weight of 328.43.
**Experimental Studies**
The 2-Hydroxymethyl olanzapine description identifies it as a significant derivative of the parent drug olanzapine. According to 2-Hydroxymethyl olanzapine technical information, this compound has been identified both as a product of biological metabolism and as a result of chemical degradation. In pharmacokinetic studies, reversed-phase HPLC with electrochemical detection was employed to analyze the presence of olanzapine and its metabolites in rat plasma, confirming the biological origin of this compound. Furthermore, forensic research has successfully identified 2-hydroxymethyl-olanzapine as a novel degradation product, which is essential for the accurate interpretation of post-mortem drug concentrations and stability testing. While specific IC50 values are not typically associated with this metabolite, its presence serves as a critical marker for olanzapine metabolism and degradation. In conclusion, 2-Hydroxymethyl olanzapine is a vital reference standard for pharmaceutical analysis and pharmacokinetic research.
Keywords
2-Hydroxymethyl olanzapine, 174756-45-7, LY-290411, 2-OH-OLZ, LY290411, LY 290411, Drug Metabolite, Olanzapine, Inhibitor, inhibitor, inhibit
References
[1] Chiu JA, et al. Analysis and pharmacokinetics of olanzapine (LY170053) and two metabolites in rat plasma using reversed-phase HPLC with electrochemical detection. J Pharm Biomed Anal. 1996 Mar;14(5):609-615.
[2] Saar E, et al. Identification of 2-hydroxymethyl-olanzapine as a novel degradation product of olanzapine. Forensic Sci Int. 2012 Jul 10;220(1-3):74-9.
**Background**
Protein arginine methyltransferases (PRMTs) play a critical role in the regulation of gene expression by catalyzing the transfer of methyl groups to arginine residues on various proteins, including histones. Among these, PRMT4 (CARM1) and PRMT6 are Type I PRMTs that primarily catalyze the formation of asymmetric dimethylarginine (ADMA). These epigenetic modifications are essential for modulating chromatin structure and transcriptional activity, and their dysregulation is frequently implicated in various diseases, including cancer. Given the importance of these enzymes in maintaining cellular homeostasis and their role in oncogenic signaling, the development of selective chemical probes to inhibit their activity is of great research significance. In this context, we will introduce a potent dual inhibitor of PRMT4 and PRMT6 – MS049.
**Definition**
MS049 is a potent, selective, and cell-active dual inhibitor of PRMT4 and PRMT6, exhibiting IC50 values of 34 nM and 43 nM, respectively.
**In Vitro Studies**
According to the MS049 description, this chemical probe is highly selective for PRMT4 and PRMT6 over a broad range of other epigenetic modifiers, including other PRMTs, PKMTs, DNMTs, KDMs, and methyllysine/methylarginine reader proteins. In terms of MS049 biological activity, in vitro studies in HEK293 cells demonstrated that MS049 (0.1-10 μM; 20 hours) reduces the H3R2me2a mark in a concentration-dependent manner with an IC50 of 0.97±0.05 μM. Furthermore, treatment with MS049 (0.1-100 μM; 72 hours) inhibits endogenous PRMT4 methyltransferase activity, resulting in reduced levels of cellular asymmetric arginine dimethylation of Med12 (Med12-Rme2a) with an IC50 of 1.4±0.1 μM. Notably, MS049 is not toxic and does not affect the growth of HEK293 cells, making it a valuable tool for studying MS049 epigenetics. In conclusion, MS049 is a potent and selective dual inhibitor of PRMT4 and PRMT6 that effectively reduces the levels of Med12me2a and H3R2me2a in cellular environments.
Keywords
MS049, 1502816-23-0, MS 049, MS-049, Histone Methyltransferase, epigenetic, modifiers, selective, arginine, dimethylation, toxic, H4R3me2a, HEK293, cells, Inhibitor
References
**Background**
L-lysine is an essential amino acid for humans that plays a critical role in various physiological processes, including protein synthesis and calcium absorption. Beyond its nutritional value, L-lysine has demonstrated significant potential in modulating immune responses and reducing inflammation. It is particularly noted for its ability to inhibit the occurrence of herpes simplex virus (HSV) infections, making it a valuable tool in virology research. Furthermore, L-lysine has been shown to alleviate pancreatic inflammation, improve gut health, and reduce the severity of diabetes-related complications. Given its broad impact on metabolism and the inflammatory response, it serves as a key molecule for studying systemic inflammatory syndromes. In this context, we will introduce a high-quality essential amino acid – L-Lysine.
**Definition**
L-Lysine is a human endogenous metabolite and microbial metabolite with a molecular weight of 146.19 and the chemical formula C6H14N2O2. According to the L-Lysine technical information, it acts as a substrate for the Cationic Amino Acid Transporter (CAT-3, SLC7A3).
**In Vitro and In Vivo Studies**
The L-Lysine biological activity has been extensively evaluated across various experimental models. In vitro studies using HEK293 JumpIN-SLC7A3 cells demonstrated that L-lysine serves as a substrate for the CAT-3 transporter with an EC50 value of 158 μM, as assessed by the fluorescent FLIPR membrane potential dye.
Regarding L-Lysine in vivo applications, the compound has shown potent protective effects in multiple mouse models. In a lipopolysaccharide (LPS)-induced mouse model of sepsis-induced acute lung injury, oral administration of L-lysine (5 or 10 mg/kg, p.o., single dose) significantly ameliorated lung injury. Specifically, it reduced lipid peroxidation, total protein content, and the lung tissue wet/dry ratio. It also decreased levels of tumor necrosis factor-alpha, interleukin-8, and macrophage inhibitory factor, while increasing the activities of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Additionally, in an L-Arginine hydrochloride-induced acute pancreatitis mouse model, L-lysine treatment (10 mg/kg, p.o., once daily for 45 days) attenuated pancreatic tissue injury. This effect was achieved by inhibiting the release of the inflammatory cytokine IL-6 and enhancing antioxidant activity, leading to significant decreases in malondialdehyde and nitric oxide levels (p < 0.001). In conclusion, L-Lysine is a versatile essential amino acid that provides significant anti-inflammatory and antioxidant benefits in models of sepsis and pancreatitis.
Keywords
L-Lysine, 56-87-1, Endogenous Metabolite, Virus Protease, HSV, Herpes simplex virus, Acute pancreatitis mice model, Anti-inflammatory activity, Acute pancreatitis, Antimicrobial activity, Inhibitor, inhibitor, inhibit
References
[1] Al-Malki AL. Suppression of acute pancreatitis by L-lysine in mice. BMC Complement Altern Med. 2015 Jun 23;15:193.
[2] Santos AMD, et al. Transitional metaplasia in intestinal epithelium of rats submitted to intestinal cystoplasty and treatment with L -lysine. Acta Cir Bras. 2017 Apr;32(4):297-306.
[3] Zhang Y, et al. L-lysine ameliorates sepsis-induced acute lung injury in a lipopolysaccharide-induced mouse model. Biomed Pharmacother. 2019 Oct;118:109307.
[4] Al-Malki AL. Suppression of acute pancreatitis by L-lysine in mice. BMC Complement Altern Med. 2015 Jun 23;15:193.
**Background**
Cancer metastasis, characterized by the migration and invasion of tumor cells into surrounding tissues and distant organs, is a primary driver of patient mortality. In various malignancies, such as hepatic and head and neck cancers, the modulation of signaling pathways and the expression of matrix metalloproteinases (MMPs) play critical roles in promoting cellular motility and tissue remodeling. Identifying agents that can inhibit these processes or induce programmed cell death is essential for developing effective therapeutic strategies. In this context, we will introduce a cationic surfactant with potential antitumor properties – Cetrimonium.
**Definition**
Cetrimonium bromide (CTAB) is an orally active cationic surfactant that targets MMP-2 and MMP-9, exhibiting both toxicity and anticancer effects.
**In Vitro and In Vivo Studies**
According to the Cetrimonium description, this compound is widely utilized not only in cancer research but also as a key reagent in DNA extraction protocols. Regarding Cetrimonium biological activity, in vitro studies using SK-HEP-1 cells demonstrated that concentrations of 1-5 μM over 24 hours did not significantly affect cell growth, with cell viability remaining above 90%. However, at 5 μM for 16-24 hours, it significantly attenuated the migration and invasion of SK-HEP-1 cells. Specifically, treatment with 5 μM for 24 hours down-regulated the protein expression of MMP-2 and MMP-9 while increasing the expression of TIMP-1 and TIMP-2, and restraining the expression of Rac1, cdc42, and RhoA. Furthermore, Cetrimonium in vitro data showed that 5 μM concentrations induced apoptosis in human head and neck cancer (HNC) cells over a period of 12-72 hours, characterized by a time-dependent activation of the caspase cascade.
Cetrimonium In Vivo evaluations have further highlighted its potential in oncology. In FaDu cell tumor-bearing mice, intraperitoneal injection of 5 mg/kg once daily for five consecutive days ablated the tumor-forming capacity of FaDu cells and delayed the growth of established tumors. Additionally, toxicity studies in Sprague-Dawley rats receiving 10-45 mg/kg via drinking water for one year revealed subacute and chronic toxicity, including reduced body weight and decreased food conversion efficiency at the highest dose. In conclusion, Cetrimonium is a cationic surfactant that inhibits cell migration and induces apoptosis, making it a valuable tool for Cetrimonium Cancer research.
Keywords
Cetrimonium, 57-09-0, CTAB, Cetyltrimethylammonium, Hexadecyltrimethylammonium, Biochemical Assay Reagents, MMP, Apoptosis, TGF-β Receptor, Matrix metalloproteinases, Transforming growth factor beta receptors, SK-HEP-1 cells, Head and neck cancer cells, FaDu cells tumor-bearing mice, Inhibitor
References
[1] Wu T K, et al. Cetrimonium bromide inhibits cell migration and invasion of human hepatic SK-HEP-1 cells through modulating the canonical and non-canonical TGF-β signaling pathways [J]. Anticancer research, 2019, 39(7): 3621-3631.
[2] Ito E, et al. Potential use of cetrimonium bromide as an apoptosis-promoting anticancer agent for head and neck cancer [J]. Molecular pharmacology, 2009, 76(5): 969-983.
[3] Isomaa B, et al. The subacute and chronic toxicity of cetyltrimethylammonium bromide (CTAB), a cationic surfactant, in the rat [J]. Archives of toxicology, 1976, 35: 91-96.
[4] Allen G C, et al. A modified protocol for rapid DNA isolation from plant tissues using cetyltrimethylammonium bromide [J]. Nature protocols, 2006, 1(5): 2320-2325.
**Background**
Sigma receptors are a class of chaperone proteins involved in various cellular processes, including protein folding, calcium signaling, and the regulation of apoptosis. Among them, the sigma 2 ($\sigma_2$) receptor is frequently overexpressed in various types of cancer cells, making it a highly attractive target for the development of selective antitumor therapies. Targeting the $\sigma_2$ receptor can lead to the induction of cell death and the modulation of drug resistance mechanisms, such as the expression of P-glycoprotein. Furthermore, recent research has explored the potential of sigma ligands in modulating protein-protein interactions related to viral infections. In this context, we will introduce a high-affinity $\sigma_2$ receptor agonist – PB28.
**Definition**
PB28 dihydrochloride is a cyclohexylpiperazine derivative that acts as a high-affinity and selective $\sigma_2$ receptor agonist ($K_i = 0.68$ nM) and a $\sigma_1$ antagonist ($K_i = 0.38$ nM).
**In Vitro and In Vivo Studies**
According to the PB28 description, this compound exhibits potent antiproliferative and cytotoxic effects across multiple cancer cell lines. PB28 in vitro studies using MCF7 and MCF7 ADR breast cancer cells demonstrated that treatment (15-25 nM; 24-48 hours) resulted in an accumulation of cells in the G0-G1 phase. The compound inhibited the growth of MCF7 and MCF7 ADR cells with $\text{IC}_{50}$ values of 25 nM and 15 nM, respectively, after a 2-day treatment. Notably, PB28 induces apoptosis through a caspase-independent pathway and reduces P-gp expression in a concentration- and time-dependent manner (approximately 60% in MCF7 and 90% in MCF7 ADR). Additionally, PB28 displays cytotoxic effects in C6 rat glioma and SK-N-SH human neuroblastoma cell lines. Beyond PB28 Cancer research, the compound has been shown to inhibit electrically evoked twitches in the guinea pig bladder and ileum ($\text{EC}_{50}$ of 2.62 $\mu$M and 3.96 $\mu$M) and modulate SARS-CoV-2-human protein-protein interactions.
PB28 in vivo evaluations in C57BL/6 female mice bearing Panc02 tumors showed that daily intraperitoneal injections (10.7 mg/mL) for two weeks significantly inhibited tumor growth and conferred a survival advantage to the mice. In conclusion, PB28 is a potent $\sigma_2$ receptor agonist with significant antitumor activity and the ability to modulate drug resistance.
Keywords
PB28, 172907-03-8, PB 28, PB-28, Sigma Receptor, Apoptosis, SARS-CoV, SARS coronavirus, COVID-19, SARS-CoV-2, interactor, cytotoxic, p-glycoprotein, cyclohexylpiperazine, antitumor
References
[1] Amalia Azzariti, et al. Cyclohexylpiperazine Derivative PB28, a sigma2 Agonist and sigma1 Antagonist Receptor, Inhibits Cell Growth, Modulates P-glycoprotein, and Synergizes With Anthracyclines in Breast Cancer. Mol Cancer Ther. 2006 Jul;5(7):1807-16.
[2] Maria Laura Pati, et al. Sigma-2 Receptor Agonist Derivatives of 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) Induce Cell Death via Mitochondrial Superoxide Production and Caspase Activation in Pancreatic Cancer. BMC Cancer. 2017 Jan 13;17(1):51.
[3] Nicola A Colabufo, et al. A New Method for Evaluating sigma(2) Ligand Activity in the Isolated Guinea-Pig Bladder. Naunyn Schmiedebergs Arch Pharmacol. 2003 Aug;368(2):106-12.
[4] Francesco Berardi, et al. Exploring the Importance of Piperazine N-atoms for sigma(2) Receptor Affinity and Activity in a Series of Analogs of 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28). J Med Chem. 2009 Dec 10;52(23):7817-28.
[5] David E Gordon, et al. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing. bioRxiv. 2020 Mar 22;2020.03.22.002386.
**Background**
The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein that plays a critical role in regulating cell growth, proliferation, and survival. Mutations in EGFR are frequently associated with various malignancies, particularly non-small cell lung cancer (NSCLC). While first- and second-generation EGFR inhibitors were initially successful, the emergence of resistance mutations, such as T790M and C797S, has significantly hindered therapeutic efficacy and led to poor clinical outcomes. Consequently, there is an urgent need for fourth-generation inhibitors capable of targeting these complex mutant forms to overcome drug resistance. In this context, we will introduce a potent EGFR inhibitor – EGFR-IN-70.
**Definition**
EGFR-IN-70 (compound 18j) is a potent EGFR inhibitor with IC50 values of 23.6 nM for EGFR LR/TM/CS and 307.5 nM for EGFR WT.
**In Vitro Studies**
According to the EGFR-IN-70 description, this compound is a conformationally constrained 4-(1-sulfonyl-3-indol)yl-2-phenylaminopyrimidine derivative. In terms of EGFR-IN-70 biological activity, the compound demonstrates significant anti-proliferative effects across multiple cell lines. In vitro studies conducted over 72 hours showed that EGFR-IN-70 suppressed the proliferation of Ba/F3-EGFR 19del/TM/CS, PC-9-OR-EGFR 19del/TM/CS, and A431-EGFR WT cells, with IC50 values of 0.052 μM, 0.644 μM, and 2.003 μM, respectively. Additionally, the compound exhibited potent antiproliferative activity against mouse BaF3 cells stably expressing the EGFR L858R/T790M/C797S mutant (IC50 = 0.036 μM).
Further investigation into the EGFR-IN-70 in vitro mechanism revealed that treatment with concentrations ranging from 0 to 1000 nM for 2 hours in Ba/F3-EGFR 19del/TM/CS and PC-9-OR-EGFR 19del/TM/CS cells effectively suppressed the phosphorylation of EGFR. Western blot analysis confirmed that EGFR-IN-70 (1, 3, 10, 30, 100, 300, and 1000 nM) dose-dependently inhibited the phosphorylation of EGFR and reduced the levels of downstream signaling ERK. Notably, the compound showed minimal cytotoxicity against mouse IL-3 dependent BaF3 cells (IC50 = 2.083 μM), indicating a degree of selectivity for mutant EGFR. In conclusion, EGFR-IN-70 is a potent fourth-generation EGFR inhibitor that effectively targets T790M/C797S mutations, making it a valuable tool for EGFR-driven cancer research.
Keywords
EGFR-IN-70, 2926716-96-1, EGFR, Epidermal growth factor receptor, ErbB-1, HER1, anticancer, phosphorylation, EGFR LR/TM/CS, EGFR WT, Inhibitor, inhibitor, inhibit
References