WM-1119是一种强效KAT6抑制剂，IC50值为6.3µM，对KAT6A、KAT5和KAT7的KD值分别为0.002µM、2.2µM和0.5µM。
Cas No.:2055397-28-7
Sample solution is provided at 25 µL, 10mM.
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WM-1119, a potent KAT6 inhibitor with an IC50 value of 6.3µM, has KD values of 0.002µM, 2.2µM, and 0.5µM for KAT6A, KAT5, and KAT7, respectively [1]. WM-1119 demonstrates effective inhibitory potency for KAT6 through unique hydrophobic interactions enabled by the 3-fluoro-5-(pyridine-2-yl)benzoyl moiety, which engages Ile647 and Gly687 in addition to the conserved contacts with Arg660, Ser690, Ser693, Leu686, and Ile649[2]. WM-1119 has been widely used to increase CDKN2A expression and inhibit leukemic cell proliferation[3].
In vitro, WM-1119 treatment for 1 hour significantly inhibited IgE-stimulated β-hexosaminidase (β-hex) release from rat basophilic leukemia-2H3 (RBL-2H3) cells with an IC50 value of 33.57μM[4]. Treatment with 10µM WM-1119 for 48h significantly inhibited the viability of HepG2 and Huh7 cells, resulting in a decrease in the number of Edu-positive cells[5]. Treatment with WM-1119 at 1µM for 7 days significantly induced proliferation arrest of MT2 cells accompanied by a significant reduction in the number of cells in S and G2 phases[6].
In vivo, Intraperitoneal injection of WM-1119 at a dose of 50mg/kg four times daily for 14 days significantly inhibited lymphoma growth and reduced tumor burden and spleen weight in C57BL/6 mice[7]. For 21 consecutive days, 60mg/kg of WM-1119 was administered intraperitoneally four times a day, in combination with cisplatin (administered intraperitoneally once every three days; 5mg/kg), which significantly inhibited tumor growth in A2780 xenografts in mice and led to a reduction in nuclear β-catenin levels in tumor tissues[8].
References:
[1] Zheng T, Wang S, Liu W, et al. Targeting KAT6A/B as a new therapeutic strategy for cancer therapy[J]. Journal of Medicinal Chemistry, 2025, 68(2): 1002-1020.
[2] Xi Z, Wang J, Ge X, et al. Dancing with KAT6A: Current advances and therapeutic potential in oncology of KAT6A inhibitors[J]. Bioorganic Chemistry, 2026: 109533.
[3] Ling V Y, Jacquelin S, Straube J, et al. Targeting Control of Cell Cycle Enhances the Activity of Conventional Chemotherapy in Chemotherapy-Resistant Acute Myeloid Leukemia[J]. Blood, 2021, 138: 2241.
[4] Baell J B, Leaver D J, Hermans S J, et al. Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth[J]. Nature, 2018, 560(7717): 253-257.
[5] Jin Y, Yang R, Ding J, et al. KAT6A is associated with sorafenib resistance and contributes to progression of hepatocellular carcinoma by targeting YAP[J]. Biochemical and Biophysical Research Communications, 2021, 585: 185-190.
[6] Sheridan M, Maqbool M A, Largeot A, et al. The small inhibitor WM-1119 effectively targets KAT6A-rearranged AML, but not KMT2A-rearranged AML, despite shared KAT6 genetic dependency[J]. Journal of hematology & oncology, 2024, 17(1): 91.
[7] Baell J B, Leaver D J, Hermans S J, et al. Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth[J]. Nature, 2018, 560(7717): 253-257.
[8] Liu W, Zhan Z, Zhang M, et al. KAT6A, a novel regulator of β-catenin, promotes tumorigenicity and chemoresistance in ovarian cancer by acetylating COP1[J]. Theranostics, 2021, 11(13): 6278.
WM-1119是一种强效KAT6抑制剂，IC50值为6.3µM，对KAT6A、KAT5和KAT7的KD值分别为0.002µM、2.2µM和0.5µM[1]。WM-1119通过自身3-fluoro-5-(pyridine-2-yl)benzoyl部分实现的独特疏水相互作用，展现出对KAT6的有效抑制效力，该部分除了与保守的Arg660、Ser690、Ser693、Leu686和Ile649接触外，还与Ile647和Gly687结合[2]。WM-1119已被广泛用于增加CDKN2A表达并抑制白血病细胞增殖[3]。
在体外，WM-1119处理1小时显著抑制了IgE刺激的大鼠嗜碱性白血病-2H3（RBL-2H3）细胞释放β-氨基己糖苷酶（β-hex），IC50值为33.57µM[4]。使用10µM的WM-1119处理48小时，显著抑制了HepG2和Huh7细胞的活力，导致Edu阳性细胞数量减少[5]。使用1µM的WM-1119处理7天，显著诱导了MT2细胞的增殖停滞，并伴随S期和G2期细胞数量的显著减少 [6]。
在体内，每日四次腹腔注射50mg/kg剂量的WM-1119，持续14天，显著抑制了C57BL/6小鼠的淋巴瘤生长，并减少了肿瘤负荷和脾脏重量[7]。连续21天每日四次腹腔注射60mg/kg剂量的WM-1119，联合顺铂（每三天腹腔注射一次；5mg/kg），显著抑制了小鼠A2780异种移植瘤的生长，并导致肿瘤组织中核β-连环蛋白水平降低[8]。
| Cell experiment [1]: | |
Cell lines | SW480 cells |
Preparation Method | SW480 cells were cultured in DMEM medium containing 10% fetal bovine serum (FBS) and 1% penicilin-streptomycin at 37℃ in the presence of 5% CO2. WM-1119 (1µM) was added to the culture medium and cultured for 24 hours, while an equal volume of DMSO was added to the control group, and cell viability was analyzed. |
Reaction Conditions | 1µM; 24h |
Applications | WM-1119 treatment significantly decreased the cell viability of SW480 cells. |
| Animal experiment [2]: | |
Animal models | Female nu/nu mice |
Preparation Method | Female nu/nu mice were housed in a specific pathogen-free (SPF) animal house maintained at 23°C with a 12h light/dark cycle and free access to water and food. A total of 1×106 A2780 cells were subcutaneously inoculated into the hind flanks of 5-week-old female nu/nu mice. Cisplatin and WM-1119 were intraperitoneally injected into mice 7 days after tumor cell inoculation at 5mg/kg and 60mg/kg, respectively. Cisplatin was injected every three days for 21 days, and WM-1119 was injected 4 times per day. The lengths and widths of the tumors were measured every 5 days, and the tumor volume was calculated according to the formula: volume= (length×width2)/2. |
Dosage form | 60mg/kg; four times a day for 21 days; i.p. |
Applications | WM-1119 treatment in combination with cisplatin led to a significant reduction in tumor burden in mice with A2780 xenografts, without affecting body weight loss. |
References: | |
| Cas No. | 2055397-28-7 | SDF | |
| 化学名 | 2-fluoro-N'-(3-fluoro-5-(pyridin-2-yl)benzoyl)benzenesulfonohydrazide | ||
| Canonical SMILES | O=C(NNS(=O)(C1=CC=CC=C1F)=O)C2=CC(C3=NC=CC=C3)=CC(F)=C2 | ||
| 分子式 | C18H13F2N3O3S | 分子量 | 389.38 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS (pH 7.2) (1:4): 0.25 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。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5682 mL | 12.8409 mL | 25.6819 mL |
| 5 mM | 513.6 μL | 2.5682 mL | 5.1364 mL |
| 10 mM | 256.8 μL | 1.2841 mL | 2.5682 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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2.
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