YKL-05-099
目录号 : GC31645
YKL-05-099是一种高选择性盐诱导激酶（SIK1: IC50 = 10nM; SIK2: IC50 = 40nM; SIK3: IC50 = 20nM）的小分子抑制剂。
Cas No.:1936529-65-5
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');)
YKL-05-099 is a highly selective small molecule inhibitor of salt-inducible kinases (SIK1: IC50 = 10nM; SIK2: IC50 = 40nM; SIK3: IC50 = 20nM) [1]. By blocking SIK-mediated phosphorylation of HDACs and CRTCs, YKL-05-099 promotes the nuclear translocation of these transcriptional regulators, thereby altering downstream gene expression [2-3]. YKL-05-099 is primarily used in research on bone metabolism, inflammation, and tumorigenesis [4].
In MLL-rearranged leukemia cells, YKL-05-099 (1nM-10μM; 72h) inhibits the growth of cells by modulating SIK3-mediated regulation of HDAC4 [5]. In primary human adipocytes YKL-05-099 (3-30μM; 1h) significantly inhibited glucose uptake, reducing both basal and submaximally insulin-stimulated uptake [6].
In KPC cell subcutaneous tumor-bearing mice model, YKL-05-099 (8mg/kg; ip; 26d) significantly enhanced the antitumor effect of gemcitabine by augmenting its cytotoxicity and promoting ferroptosis, as evidenced by decreased Ki67 expression and increased 4-HNE and Fe²⁺ levels [7]. In collagen-induced arthritis (CIA) mouse model, treatment with YKL-05-099 (20mg/kg; ip; single injection) significantly reduced joint and bone destruction and immune cell infiltration, reduced TUNEL⁺ apoptotic cells in synovial tissue, and enhanced the clearance of apoptotic cells by macrophages, thereby improving the symptoms of rheumatoid arthritis [8].
References:
[1]. Sundberg T B, Liang Y, Wu H, et al. Development of chemical probes for investigation of salt-inducible kinase function in vivo[J]. ACS chemical biology, 2016, 11(8): 2105-2111.
[2]. Jagannath A, Taylor L, Ru Y, et al. The multiple roles of salt-inducible kinases in regulating physiology[J]. Physiological reviews, 2023, 103(3): 2231-2269.
[3]. Wein M N, Liang Y, Goransson O, et al. SIKs control osteocyte responses to parathyroid hormone[J]. Nature communications, 2016, 7(1): 13176.
[4]. Momenzadeh K, Yeritsyan D, Abbasian M, et al. Stimulation of fracture mineralization by salt-inducible kinase inhibitors[J]. Frontiers in Bioengin
[5]. Tarumoto Y, Lin S, Wang J, et al. The Salt-Inducible Kinase inhibitor YKL-05-099 suppresses MEF2C function and acute myeloid leukemia progression in vivo[J]. bioRxiv, 2019: 636969.
[6]. Säll J, Lindahl M, Fritzen A M, et al. Salt‐inducible kinases are required for glucose uptake and insulin signaling in human adipocytes[J]. Obesity, 2023, 31(10): 2515-2529.
[7]. Zhang H, Ma T, Wen X, et al. SIK1 promotes ferroptosis resistance in pancreatic cancer via HDAC5-STAT6-SLC7A11 axis[J]. Cancer Letters, 2025, 623: 217726.
[8]. Lee M, Kim M K, Mo S, et al. Inhibition of salt-inducible kinases resolves autoimmune arthritis by promoting macrophage efferocytosis[J]. Signal Transduction and Targeted Therapy, 2025, 10(1): 293.
YKL-05-099是一种高选择性盐诱导激酶（SIK1: IC50 = 10nM; SIK2: IC50 = 40nM; SIK3: IC50 = 20nM）的小分子抑制剂 [1]。通过阻断SIK介导的HDAC和CRTC磷酸化，YKL-05-099促进这些转录调控因子的核转位，从而改变下游基因的表达 [2-3]。YKL-05-099主要用于骨代谢、炎症和肿瘤发生研究 [4]。
在MLL重排的白血病细胞中，YKL-05-099（1nM-10μM; 72h）通过调节SIK3介导的HDAC4调控来抑制细胞生长 [5]。在原代人脂肪细胞中，YKL-05-099（3-30μM；1h）显著抑制葡萄糖摄取，降低基础和亚最大胰岛素刺激的摄取 [6]。
在KPC细胞皮下移植瘤小鼠模型中，YKL-05-099（8mg/kg；ip；26d）显著增强了gemcitabine的抗肿瘤作用，增强了其细胞毒性并促进了铁死亡，其证据是Ki67表达降低、4-HNE和Fe²⁺水平升高 [7]。在胶原诱导性关节炎（CIA）小鼠模型中，用YKL-05-099（20mg/kg；ip；单次注射）治疗可显著减少关节和骨骼破坏以及免疫细胞浸润，减少滑膜组织中的TUNEL⁺凋亡细胞，增强巨噬细胞对凋亡细胞的清除，从而改善类风湿性关节炎症状 [8]。
| Cell experiment [1]: | |
Cell lines | MLL-rearranged leukemia cells |
Preparation Method | For EC₅₀ determination, 1,000 cells were seeded in opaque 96-well plates and treated with serially diluted concentrations of YKL-05-099 or 0.1% DMSO as a control. After 72 hours of incubation, cell viability was measured using the CellTiter-Glo Luminescent Cell Viability Assay Kit according to the manufacturer’s instructions, and luminescence was detected with a SpectraMax plate reader. Data were analyzed using GraphPad Prism software. For Western blot analysis, cells were harvested after YKL-05-099 treatment at the indicated concentrations and time points. |
Reaction Conditions | 1nM-10μM; 72h |
Applications | YKL-05-099 inhibits the growth of MLL-rearranged leukemia cells by modulating SIK3-mediated regulation of HDAC4. |
| Animal experiment [2]: | |
Animal models | KPC cell subcutaneous tumor-bearing mice model |
Preparation Method | 5×103 KPC cells were injected into the pancreatic tissue of 6-week-old C57BL/6 mice. Gemcitabine (30mg/kg), YKL-05-099 (8mg/kg), or a combination of the two was administered on day 12 after implantation. Tumor diameters were measured with calipers every three days throughout the treatment period. |
Dosage form | 8mg/kg; ip; 26d |
Applications | YKL-05-099 significantly enhanced the antitumor effect of gemcitabine by augmenting its cytotoxicity and promoting ferroptosis, as evidenced by decreased Ki67 expression and increased 4-HNE and Fe²⁺ levels. |
References: | |
| Cas No. | 1936529-65-5 | SDF | |
| Canonical SMILES | O=C1N(C2=NC=C(OC)C=C2)C3=NC(NC4=CC=C(C5CCN(C)CC5)C=C4OC)=NC=C3CN1C6=C(C)C=CC=C6Cl | ||
| 分子式 | C32H34ClN7O3 | 分子量 | 600.11 |
| 溶解度 | DMSO : ≥ 75 mg/mL (124.98 mM);Water : < 0.1 mg/mL (insoluble) | 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 | 1.6664 mL | 8.3318 mL | 16.6636 mL |
| 5 mM | 333.3 μL | 1.6664 mL | 3.3327 mL |
| 10 mM | 166.6 μL | 833.2 μL | 1.6664 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%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet