ASTX029 (ERK1/2 inhibitor 2)是一种高效且选择性的具有口服生物利用活性的细胞外信号调节激酶（ERK）1/2抑制剂（对于ERK2的IC50为2.7nM）。
Cas No.:2095719-92-7
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');)
ASTX029 (ERK1/2 inhibitor 2) is a highly effective and selective orally bioavailable extracellular signal-regulated kinase (ERK) 1/2 inhibitor (with an IC50 of 2.7nM for ERK2) [1]. ERK1/2 is the terminal kinase in the MAPK pathway, and the activation of the ERK/MAPK pathway is very common in myeloid malignancies [2]. ASTX029 has anti-tumor activity and can be used for cancer treatment [3].
In vivo, ASTX029 (10 and 100nM; 0-72h) can induce cell cycle arrest at the G1 phase in A375 and HCT116 cells and induce apoptosis [4]. ASTX029 (0.1-5nM; 12h) significantly reduced the p-ERK level in primary microglial cells stimulated by lipopolysaccharide (LPS) and inhibited the secretion of IL-1β, IL-6 and TNF-α [5].
In vivo, ASTX029 (50μM; 1μl; intravitreal injection) significantly reduced the p-ERK level in the retina of laser-induced choroidal neovascularization (CNV) mice and reduced the lesion area of CNV [5]. ASTX029 (20-75mg/kg/day; oral) can significantly inhibit tumor growth in Colo205 (BRAFV600E-mutant colorectal cancer) tumor-bearing mice [4].
References:
[1] Munck, J., Berdini, V., Courtin, A., et al. The clinical candidate, ASTX029, is a novel, dual mechanism ERK1/2 inhibitor and has potent activity in MAPK-activated cancer cell lines and in vivo tumor models. Eur. J. Cancer 138(Suppl 2), S53 (2020)
[2] Sharma P, Piya S, Baran N, et al. P460: ERK1/2 inhibition overcomes ressitance to BCL2 inhibition in acute myeloid leukemia by impact on mitochondrial dynamics and function[J]. HemaSphere, 2023, 7(Suppl): e08176db.
[3] Hindley C J, Fazal L, Munck J M, et al. Anti-tumor activity of ASTX029, a dual mechanism inhibitor of ERK1/2, in preclinical AML models[J]. Blood, 2020, 136: 7-8.
[4] Munck JM, et al. ASTX029, a Novel Dual-mechanism ERK Inhibitor, Modulates Both the Phosphorylation and Catalytic Activity of ERK. Mol Cancer Ther. 2021 Oct;20(10):1757-1768.
[5] Zou Y, Jiang J, Li Y, et al. Immune Checkpoint PD‐L1 Modulates Retinal Microglial Activation to Alleviate Vascular Leakage in Choroidal Neovascularization via ERK[J]. Advanced Science, 2025: 2400747.
ASTX029 (ERK1/2 inhibitor 2)是一种高效且选择性的具有口服生物利用活性的细胞外信号调节激酶（ERK）1/2抑制剂（对于ERK2的IC50为2.7nM）[1]。ERK1/2是MAPK通路中的末端激酶，ERK/MAPK通路的激活在髓系恶性肿瘤中很常见 [2]。ASTX029具有抗肿瘤活性，可用于癌症的治疗 [3]。
在体外，ASTX029（10和100nM; 0-72h）能够诱导A375和HCT116细胞的细胞周期停滞在G1期，并诱导凋亡 [4]。ASTX029（0.1-5nM; 12h）显著降低了脂多糖（LPS）刺激的原代小胶质细胞中的p-ERK水平，并抑制了IL-1β，IL-6和TNF-α的分泌 [5]。
在体内，ASTX029（50μM; 1μl;玻璃体内注射）显著降低了激光诱导的脉络膜新生血管（CNV）小鼠的视网膜p-ERK水平并减少了CNV病变面积 [5]。ASTX029（20-75mg/kg/day; oral）能够显著抑制Colo205（BRAFV600E-突变型结直肠癌）荷瘤小鼠的肿瘤生长 [4]。
| Cell experiment [1]: | |
Cell lines | Primary microglia cells |
Preparation Method | Primary microglia cells were plated in 96-well plates at a density of 2000 cells per well and incubated in FBS-free medium for 12h prior to treatment. Treatments included ASTX029 at concentrations of 0.1, 0.5, 1, 5nM. Collect the cell culture supernatant for ELISA testing. |
Reaction Conditions | 0.1-5nM; 12h |
Applications | ASTX029 significantly inhibited the secretion of IL-1β, IL-6 and TNF-α in primary microglial cells. |
| Animal experiment [1]: | |
Animal models | PD-L1 KO mice with a C57BL/6 background |
Preparation Method | Mice were anesthetized by intraperitoneal injection of 1% pentobarbital sodium (40mg kg−1). Pupil dilation was achieved using 0.5% tropicamide eye drops. A diode laser system, designed in a slit-lamp style, employing a green laser at 532nm with a power of 100mW, a duration of 100ms, and a spot size of 100µm, was utilized. For intravitreal delivery, mice were anesthetized, and a 34-gauge needle was inserted into the vitreous space approximately 1.5mm below the limbus, and 1µL ASTX029 was administered bilaterally with a Nanofil syringe. The fundus photography and fluorescein fundus angiography (FFA) examination were conducted at 7 days post-laser photocoagulation. |
Dosage form | 50μM; 1μl; Intravitreal injection |
Applications | ASTX029 significantly reduced the lesion area of the retina in mice with laser-induced choroidal neovascularization (CNV). |
References: | |
| Cas No. | 2095719-92-7 | SDF | |
| Canonical SMILES | ClC(C(C1=CC2=C(CN([C@H](C)C(N[C@H](CO)C3=CC(F)=CC(OC)=C3)=O)C2=O)C=C1)=N4)=CN=C4NC5CCOCC5 | ||
| 分子式 | C29H31ClFN5O5 | 分子量 | 584.04 |
| 溶解度 | DMSO: 250 mg/mL (428.05 mM) | 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 | 1.7122 mL | 8.5611 mL | 17.1221 mL |
| 5 mM | 342.4 μL | 1.7122 mL | 3.4244 mL |
| 10 mM | 171.2 μL | 856.1 μL | 1.7122 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: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet