Bobcat 339
(Synonyms: BC339) 目录号 : GC46935
Bobcat 339是一种具有良好选择性的新型胞嘧啶类TET酶抑制剂，对TET1和TET2的IC50值分别为33μM和73μM，但不抑制DNA甲基转移酶DNMT3a。
Cas No.:2280037-51-4
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Bobcat 339 is a novel cytosine-based TET enzyme inhibitor with good selectivity, exhibiting IC50 values of 33μM for TET1 and 73μM for TET2 without inhibiting the DNA methyltransferase DNMT3a[1]. TET enzymes are key epigenetic modifiers that facilitate DNA demethylation and regulate cell differentiation and development[2]. By competitively inhibiting the TET-mediated oxidation of 5-methylcytosine (5mC), Bobcat 339 is particularly suitable for investigating TET functions in epigenetic studies and elucidating mechanisms in relevant disease models[3,4].
In vitro, treatment of mouse hippocampal neuronal HT-22 cells with 10μM Bobcat 339 (in 1%DMSO) for 24h significantly reduced global levels of 5-hydroxymethylcytosine (5hmC)[1]. Incubation of mouse hypothalamic GT1-7 neuronal cells with 10μM Bobcat 339 for 6h decreased TET3 protein expression without affecting its mRNA abundance[5]. Furthermore, 72h treatment of human breast cancer MDA-MB-231 cells with 25μM Bobcat 339 downregulated FANCA gene expression and significantly inhibited cell proliferation via TET inhibition[6].
In vivo, intraperitoneal injection of Bobcat 339 (2.5mg/kg) in mice with GFP-specific expression in agouti-related petide (AgRP) neurons of the hypothalamus resulted in a notable reduction in TET3-positive AgRP neurons within 2 days, accompanied by increased neuronal activation (indicated by elevated FOS protein expression)[5]. In C57BL/6 mice with transient middle cerebral artery occlusion (tMCAO) and a lipopolysaccharide (LPS)-induced (10mg/kg; i.p.) hyperinflammatory state, intravenous administration of Bobcat 339 (10mg/kg/day) for 3 consecutive days significantly reduced cerebral infarct volume and improved neurological functional recovery[7].
References:
[1] CHUA G N L, WASSARMAN K L, SUN H, et al. Cytosine-based TET enzyme inhibitors[J]. ACS Medicinal Chemistry Letters, 2019, 10(2): 180-185.
[2] WEIRATH N A, HURBEN A K, CHAO C, et al. Small molecule inhibitors of TET dioxygenases: Bobcat339 activity is mediated by contaminating copper (II)[J]. ACS Medicinal Chemistry Letters, 2022, 13(5): 792-798.
[3] FENG J, SHAO N, SZULWACH K E, et al. Role of Tet1 and 5-hydroxymethylcytosine in cocaine action[J]. Nature Neuroscience, 2015, 18(4): 536-544.
[4] XU Y, YANG Y, WANG Z, et al. ZNF397 deficiency triggers TET2-driven lineage plasticity and AR-targeted therapy resistance in prostate cancer[J]. Cancer Discovery, 2024, 14(8): 1496-1521.
[5] LV H, CATARINO J, LI D, et al. A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model[J]. Proceedings of the National Academy of Sciences, 2023, 120(16): e2300015120.
[6] LUO L, YUAN F, PALOVCAK A, et al. Oncogenic properties of wild-type DNA repair gene FANCA in breast cancer[J]. Cell Reports, 2025, 44(4): 115480.
[7] WANG Y, ZHANG L, LYU T, et al. Association of DNA methylation/demethylation with the functional outcome of stroke in a hyperinflammatory state[J]. Neural Regeneration Research, 2024, 19(10): 2229-2239.
Bobcat 339是一种具有良好选择性的新型胞嘧啶类TET酶抑制剂，对TET1和TET2的IC50值分别为33μM和73μM，但不抑制DNA甲基转移酶DNMT3a[1]。TET酶是关键的表观遗传修饰因子，可以促进DNA去甲基化并调控细胞的分化和发育[2]。Bocat 339可竞争性地抑制TET介导的5-methylcytosine（5mC）氧化过程,故适用于表观遗传学研究中TET酶功能探索和相关疾病模型的机制解析[3,4]。
在体外，Bobcat 339（10μM）在1%DMSO中处理小鼠海马神经元HT-22细胞系24h，可显著降低细胞整体的5-hydroxymethylcytosine（5hmC）水平[1]。Bobcat 339（10μM）与小鼠下丘脑GT1-7神经元细胞共同孵育6h，降低了TET3蛋白水平，而不影响mRNA丰度[5]。Bobcat 339（25μM）处理人乳腺病变MDA-MB-231细胞系72h，TET的抑制会下调FANCA基因的表达，并显著抑制细胞的增殖[6]。
在体内，Bobcat 339（2.5mg/kg）通过腹腔注射治疗下丘脑agouti-related peptide（AgRP）神经元中特异性表达GFP的小鼠，2天后TET3阳性的AgRP神经元数量明显减少，同时这些神经元被激活（FOS蛋白表达增加）[5]。Bobcat 339（10mg/kg/day）通过尾静脉注射给药经脂多糖LPS（10mg/kg; i.p.）诱导的高炎症脑缺血小鼠C57BL/6，连续给药3天后显著减少了梗死体积，改善了神经功能缺损[7]。
| Cell experiment [1]: | |
Cell lines | HT-22 (mouse hippocampal neuronal cell line) |
Preparation Method | HT-22 cells were treated with 10μM Bobcat 339 in 1% DMSO for 24h and lysed. DNA was extracted, and 5hmC levels were detected using a 5hmC-specific antibody, allowing for percent 5hmC of all cytosine species to be determined by colorimetric detection. |
Reaction Conditions | 10μM; 24h |
Applications | Cells treated with Bobcat 339 had significantly reduced global 5hmC levels as compared to the vehicle control, demonstrating its ability to reduce DNA 5hmC abundance by inhibiting TET enzyme function in living cells. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice with transient middle cerebral artery occlusion (tMCAO) and an LPS-induced (10mg/kg; i.p.) hyperinflammatory state |
Preparation Method | Bobcat 339 was dissolved in dimethylsulfoxide and diluted in saline at a concentration of 1mg/mL. Bobcat 339 (10mg/kg/day) was administrated by tail vein injection 3 days before surgery, followed by daily injection once a day until the date of surgery. All mice were subjected to intraperitoneal injections of LPS (10mg/kg) to induce hyperinflammation at the onset of tMCAO. Reagents were administered again at the onset of reperfusion to ensure the efficacy. All mice underwent behavioral testing at 24h after surgery. |
Dosage form | 10mg/kg/day; 3 days; i.v. |
Applications | Treatment with Bobcat 339 (10mg/kg/day; 3 days; i.v.) significantly reduced cerebral infarct volume and improved neurological and motor deficits in C57BL/6 mice subjected to tMCAO and LPS-induced (10mg/kg; i.p.) hyperinflammatory state. |
References: | |
| Cas No. | 2280037-51-4 | SDF | |
| 别名 | BC339 | ||
| Canonical SMILES | O=C1N=C(C(Cl)=CN1C2=CC=CC(C3=CC=CC=C3)=C2)N | ||
| 分子式 | C16H12ClN3O | 分子量 | 297.7 |
| 溶解度 | DMF: 1 mg/ml,DMSO: 1 mg/ml,DMSO:PBS (pH 7.2) (1:8): 0.11 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.3591 mL | 16.7954 mL | 33.5909 mL |
| 5 mM | 671.8 μL | 3.3591 mL | 6.7182 mL |
| 10 mM | 335.9 μL | 1.6795 mL | 3.3591 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet