SHIN1
(Synonyms: RZ-2994) 目录号 : GC32773
SHIN1（RZ2994）是丝氨酸羟甲基转移酶1（SHMT1）和SHMT2的抑制剂，IC50分别为5nM和13nM。
Cas No.:2146095-85-2
Sample solution is provided at 25 µL, 10mM.
SHIN1 (RZ2994) is an inhibitor of serine hydroxymethyltransferase 1 (SHMT1) and SHMT2, with IC50 values of 5nM and 13nM, respectively[1, 2]. SHIN1 can competitively bind to folate, penetrate cell membranes, and exhibits anti-cancer activity[3].
In vitro, treatment of murine peritoneal macrophages with SHIN1 (10μM) for 6h dose-dependently reduced the LPS-induced increase in IL-1β and IL-1α mRNA expression, as well as precursor IL-1β protein levels, without affecting TNF-α[4]. Treatment of human keratinocyte cell line HaCaT cells with SHIN1 (2μM) for 24h significantly reduced the IL-17-induced increase in Defb4, Lcn2, S100a9, and IL-1β expression[5].
In vivo, intraperitoneal injection of SHIN1 (100mg/kg/day) for 14 days in mice bearing RPMI8402 xenograft tumors significantly reduced leukemia burden in the bone marrow and spleen[6].
References:
[1] He L, Endress J, Cho S, et al. Suppression of nuclear GSK3 signaling promotes serine/one-carbon metabolism and confers metabolic vulnerability in lung cancer cells[J]. Science advances, 2022, 8(20): eabm8786.
[2] Ducker G S, Ghergurovich J M, Mainolfi N, et al. Human SHMT inhibitors reveal defective glycine import as a targetable metabolic vulnerability of diffuse large B-cell lymphoma[J]. Proceedings of the National Academy of Sciences, 2017, 114(43): 11404-11409.
[3] García-Cañaveras J C, Lancho O, Ducker G S, et al. SHMT inhibition is effective and synergizes with methotrexate in T-cell acute lymphoblastic leukemia[J]. Leukemia, 2021, 35(2): 377-388.
[4] Yu W, Wang Z, Zhang K, et al. One-carbon metabolism supports S-adenosylmethionine and histone methylation to drive inflammatory macrophages[J]. Molecular cell, 2019, 75(6): 1147-1160. e5.
[5] Lee J Y, Lee J H, Lim H J, et al. Aminooxy acetic acid suppresses Th17-mediated psoriasis-like skin inflammation by inhibiting serine metabolism[J]. Frontiers in Pharmacology, 2023, 14: 1215861.
[6] Pikman Y, Ocasio-Martinez N, Alexe G, et al. Targeting serine hydroxymethyltransferases 1 and 2 for T-cell acute lymphoblastic leukemia therapy[J]. Leukemia, 2022, 36(2): 348-360.
SHIN1（RZ2994）是丝氨酸羟甲基转移酶1（SHMT1）和SHMT2的抑制剂，IC50分别为5nM和13nM[1, 2]。SHIN1能够与叶酸竞争结合、能够穿透细胞膜，具有抗癌活性[3]。
在体外，SHIN1（10μM）处理小鼠腹腔巨噬细胞6h，剂量依赖性地降低了LPS诱导的IL-1β和IL-1α mRNA表达水平升高，以及前体IL-1β蛋白，但未影响TNF-α[4]。SHIN1（2μM）处理人表皮角质细胞系HaCaT细胞24h，显著降低了IL-17刺激引起的Defb4、Lcn2、S100a9和IL-1β表达水平升高[5]。
在体内，SHIN1（100mg/kg/day）通过腹腔注射治疗RPMI8402细胞异种移植小鼠14天，显著降低了小鼠骨髓和脾脏中的白血病负担[6]。
| Cell experiment [1]: | |
Cell lines | Mouse peritoneal macrophages |
Preparation Method | Cells (5×105 per well) were seeded in 12-well plates in complete DMEM to adhere, then washed with PBS and starved in amino acid-deficient (serine, glycine, or methionine) DMEM medium supplemented with 10% dialyzed FBS and 1% penicillin/streptomycin for 12h. After that, cells were stimulated with LPS (500ng/mL) for 6h in the presence of SHIN1 (10μM) as indicated, and harvested for qPCR and Western Blot. |
Reaction Conditions | 10μM; 6h |
Applications | SHIN1 dose dependently reduced the LPS-induced IL-1β and IL-1α mRNA levels, as well as pro-IL-1β protein but not TNF-α. |
| Animal experiment [2]: | |
Animal models | Female NSG mice |
Preparation Method | 500,000 cells RPMI8402 luciferase-expressing cells were injected via tail vein into 8-week-old, female NSG mice. Leukemia burden was assessed using bioluminescence imaging by injecting mice intraperitoneally with 75mg/kg d-Luciferin, anesthetizing them with 2-3% isoflurane, and imaging them on an IVIS Spectrum. A standardized region of interest (ROI) encompassing the entire mouse was used to determine total body bioluminescence, with data expressed as photons/s/ROI (ph/s/ROI). Upon detectable bioluminescence, mice were separated into two cohorts, 7 per cohort, and treated with SHIN1 100mg/kg i.p. or vehicle daily for 14 days. |
Dosage form | 100mg/kg/day; 14 days; i.p. |
Applications | SHIN1 treatment led to a decrease in leukemia burden in the bone marrow and spleen. |
References: | |
| Cas No. | 2146095-85-2 | SDF | |
| 别名 | RZ-2994 | ||
| Canonical SMILES | OCC1=CC(C2=CC=CC=C2)=CC(C3(C(C(C)=NN4)=C4OC(N)=C3C#N)C(C)C)=C1 | ||
| 分子式 | C24H24N4O2 | 分子量 | 400.47 |
| 溶解度 | DMSO : ≥ 50 mg/mL (124.85 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 | 2.4971 mL | 12.4853 mL | 24.9707 mL |
| 5 mM | 499.4 μL | 2.4971 mL | 4.9941 mL |
| 10 mM | 249.7 μL | 1.2485 mL | 2.4971 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