BAY 2416964
目录号 : GC60622
BAY 2416964是一种强效且具有口服活性的芳烃受体（AhR）抑制剂，IC50值为341nM。
Cas No.:2242464-44-2
Sample solution is provided at 25 µL, 10mM.
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BAY 2416964 is a potent and orally active inhibitor targeting aryl hydrocarbon receptor (AhR) with IC50 value of 341nM[1]. BAY 24169649 has been widely used in anti-cancer research[2].
In vitro, BAY 2416964 strongly inhibited the expression of CYP1A1 induced by AhR in human monocyte U937 cells with IC50 value of 21nM after treatment for 4h[3]. After treatment with 10nM BAY 2416964 for 24 hours, the expression of IL-10 in Tet2-deficient B cells was significantly inhibited[4]. Treatment with 100nM BAY 2416964 for 24 hours could significantly inhibit the expression of fibrotic factors (Fn, Col1a1 and α-SMA) induced by l-Kynurenine (100μM; 24h) and alleviate the fibrotic process in TCMK-1 cells[5]. BAY 2416964 treatment (20µM; 48h) increased the expression of type I interferon and raised the levels of IFNB1, CXCL10 and CCL5 in MDA-MB-436 cells[6].
In vivo, BAY 2416964 (20mg/kg/day; i.p.) treatment for one week can inhibit the expression of EZH2 caused by cisplatin (20mg/kg/day; i.p.) in the kidneys of C57BL/6 J mice, and alleviate cisplatin-induced renal dysfunction and tubular injury[7]. Treatment with BAY 2416964 (p.o.) at a dose of 30mg/kg/day for half a month enhanced the production of IFN-γ and increased the frequency of immune-stimulated tumor-infiltrating CD8+ T cells and natural killer (NK) cells, inhibited tumor growth in the melanoma mouse model[3].
References:
[1] Gutcher I, Schmees N, Röse L, et al. 2-Heteroaryl-3-oxo-2, 3-dihydropyridazine-4-carboxamides for the treatment of cancer: U.S. Patent 11,795,164[P]. 2023-10-24.
[2] Cohen Z, Petrenko E, Barisaac A S, et al. SLAYER: A Computational Framework for Identifying Synthetic Lethal Interactions through Integrated Analysis of Cancer Dependencies[J]. bioRxiv, 2024: 2024.05. 01.592073.
[3] Kober C, Roewe J, Schmees N, et al. Targeting the aryl hydrocarbon receptor (AhR) with BAY 2416964: a selective small molecule inhibitor for cancer immunotherapy[J]. Journal for Immunotherapy of Cancer, 2023, 11(11): e007495.
[4] Lu Z, Liu R, Wang Y, et al. Ten‐eleven translocation‐2 inactivation restrains IL‐10‐producing regulatory B cells to enable antitumor immunity in hepatocellular carcinoma[J]. Hepatology, 2023, 77(3): 745-759.
[5] Ren Q, Cheng L, Guo F, et al. Fisetin improves hyperuricemia-induced chronic kidney disease via regulating gut microbiota-mediated tryptophan metabolism and aryl hydrocarbon receptor activation[J]. Journal of Agricultural and Food Chemistry, 2021, 69(37): 10932-10942.
[6] Martin J C, da Silva Fernandes T, Chaudhry K A, et al. Aryl hydrocarbon receptor suppresses STING-mediated type I IFN expression in triple-negative breast cancer[J]. Scientific Reports, 2024, 14(1): 5731.
[7] Wen L, Ren Q, Guo F, et al. Tubular aryl hydratocarbon receptor upregulates EZH2 to promote cellular senescence in cisplatin-induced acute kidney injury[J]. Cell Death & Disease, 2023, 14(1): 18.
BAY 2416964是一种强效且具有口服活性的芳烃受体（AhR）抑制剂，IC50值为341nM[1]。BAY 2416964已被广泛应用于抗癌研究领域[2]。
在体外，BAY 2416964处理4小时后能显著抑制人单核细胞U937中AhR诱导的CYP1A1表达（IC50值为21nM）[3]。使用10nM BAY 2416964处理24小时可明显抑制Tet2缺陷型B细胞中IL-10的表达[4]。在TCMK-1细胞中，100nM的BAY 2416964处理24小时能显著抑制L-犬尿氨酸（100μM；24小时）诱导的纤维化因子（Fn、Col1a1和α-SMA）表达，缓解纤维化进程[5]。MDA-MB-436细胞经BAY 2416964（20µM；48小时）处理后，I型干扰素表达增加，IFNB1、CXCL10和CCL5水平升高[6]。
在体内，C57BL/6J小鼠连续一周腹腔注射BAY 2416964（20mg/kg/day）可抑制顺铂（20mg/kg/day；腹腔注射）引起的肾脏EZH2表达，改善顺铂诱导的肾功能障碍和肾小管损伤[7]。在黑色素瘤小鼠模型中，口服BAY 2416964（30mg/kg/day）处理半个月能促进IFN-γ生成，增加肿瘤浸润CD8+T细胞和自然杀伤（NK）细胞的频率，并抑制肿瘤生长[3]。
| Cell experiment [1]: | |
Cell lines | PyMT mouse mammary cancer cells |
Preparation Method | PyMT mouse mammary cancer cells grew in a DMEM/F12 medium mixture that included 10% v/v fetal bovine serum and 1% v/v l-glutamine along with 1µg/ml hydrocortisone and 5µg/ml insulin and 5ng/ml epidermal growth factor. The cells underwent incubation at 37°C and 5% CO2 within a humidified environment until they reached 80% confluency before sub-culturing. PyMT cells were seeded into a 24-well plate at 5×104cells per well and received treatment with BAY 2416964 at concentrations of 0.1, 1 and 10μM for a period of 6 hours. The RNA isolation kit was used to extract RNA according to the manufacturer's instructions. The cell harvest and lysis process employed 10mM Tris-HCl buffer mixed with 1mM EDTA and 1% SDS to achieve pH 8.0. Samples underwent high intensity sonication for a total of two cycles each lasting thirty seconds with an on/off sequence. The NE-PER Nuclear and Cytoplasmic Extraction Reagents kit according to manufacturer’s instructions was used to harvest cytoplasmic and nuclear fractions. The BCA Protein Assay Kit was used to determine the protein concentration. Protein samples moved through 4-20% SDS-PAGE gels before transfer to polyvinylidene fluoride membranes. The membranes underwent overnight incubation at 4°C with primary antibodies dissolved in 5% skim milk before being treated with secondary antibodies at room temperature for 1 hour. The antibodies used in the experiment included anti-AHR (bml-sa210-0100), anti-PARP1 (sc-7150), anti-CASPASE-3 (9662S), anti-Lamin A/C (2032S), anti-Tubulin (T5168) and anti-β-actin (AC-74). Commercial extended duration substrate was used to visualize the protein bands. |
Reaction Conditions | 0.1, 1 and 10μM; 6h |
Applications | BAY 2416964 dose-dependently reduced the AHR signal transduction pathway, lowered the expression level of AHR protein, and decreased the expression level of Cyp1b1. |
| Animal experiment [2]: | |
Animal models | Male C57BL/Ly5.1 mice |
Preparation Method | The antitumor activity of BAY 2416964 was tested using the B16F10-OVA (clone 5) melanoma model in male C57BL/Ly5.1 mice. The mice were treated orally (p.o.) The mice received BAY 2416964 (30mg/kg/day) or vehicle treatment for a period of 14 days. Researchers collected tumor samples from all groups at the study's conclusion and used flow cytometry to measure different immune cell population percentages. |
Dosage form | 30mg/kg/day for 14 days; p.o. |
Applications | The BAY 2416964 treatment substantially reduced tumor expansion while raising immunostimulatory CD8+ T cells and natural killer (NK) cell levels within tumors in male C57BL/Ly5.1 mice. |
References: | |
| Cas No. | 2242464-44-2 | SDF | |
| Canonical SMILES | O=C(C1=CC(C2=CC=C(Cl)C=C2)=NN(C3=CN(C)N=C3)C1=O)N[C@@H](C)CO | ||
| 分子式 | C18H18ClN5O3 | GC40165分子量 | 387.82 |
| 溶解度 | DMSO: 250 mg/mL (644.63 mM) | 储存条件 | Store at -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5785 mL | 12.8926 mL | 25.7852 mL |
| 5 mM | 0.5157 mL | 2.5785 mL | 5.157 mL |
| 10 mM | 0.2579 mL | 1.2893 mL | 2.5785 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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Quality Control & SDS
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- Purity: >99.50%
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