RITA (NSC 652287)是一种三环噻吩衍生物，可结合p53dN（Kd=1.5nM）并阻断p53-HDM-2相互作用，抑制p53泛素化。
Cas No.:213261-59-7
Sample solution is provided at 25 µL, 10mM.
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RITA (NSC 652287) is a tricyclic thiophene derivative that binds to p53dN (Kd=1.5nM) and blocks the p53-HDM-2 interaction, thereby inhibiting p53 ubiquitination. RITA can be used in research related to various cancers (such as colorectal cancer, renal cancer, cervical cancer, etc.)[1-4].
In vitro, p53-positive tumor cells (e.g., HCT116, MCF-7) were treated with RITA (1–5μM) for 16–24 hours. Under both normoxic and hypoxic conditions, RITA significantly induced p53-dependent apoptosis while downregulating the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF)[5]. HCT116 ARID1A-/- cells were treated with RITA (0.02–50μM) for 72 hours. RITA significantly induced apoptosis, upregulated the expression of pro-apoptotic genes PUMA and NOXA, and downregulated p21 expression[6].
In vivo, RITA (10mg/kg; once daily) was administered via intraperitoneal injection to BALB/c nude mice bearing HN4-cisR head and neck cancer xenografts for 35 days. RITA alone did not significantly inhibit tumor growth, but when combined with 3-MA, RITA significantly suppressed tumor growth[7]. RITA (10mg/kg; once daily) was administered via intraperitoneal injection to NMRI-nu/nu nude mice bearing Rh36 rhabdomyosarcoma xenografts for 20 days. RITA significantly inhibited the growth of rhabdomyosarcoma xenograft tumors[8].
References:
[1] Issaeva N, Bozko P, Enge M, et al. Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med. 2004 Dec;10(12):1321-8.
[2] Nieves-Neira W, Rivera MI, Kohlhagen G, et al. DNA protein cross-links produced by NSC 652287, a novel thiophene derivative active against human renal cancer cells. Mol Pharmacol. 1999 Sep;56(3):478-84.
[3] Zhao CY, Szekely L, Bao W, et al. Rescue of p53 function by small-molecule RITA in cervical carcinoma by blocking E6-mediated degradation. Cancer Res. 2010 Apr 15;70(8):3372-81. doi: 10.1158/0008-5472.CAN-09-2787. Erratum in: Cancer Res. 2017 Jul 1;77(13):3719.
[4] Gottlieb A, Althoff K, Grunewald L, et al. RITA displays anti-tumor activity in medulloblastomas independent of TP53 status. Oncotarget. 2017 Apr 25;8(17):27882-27891.
[5] Yang J, Ahmed A, Poon E, et al. Small-molecule activation of p53 blocks hypoxia-inducible factor 1alpha and vascular endothelial growth factor expression in vivo and leads to tumor cell apoptosis in normoxia and hypoxia. Mol Cell Biol. 2009 Apr;29(8):2243-53.
[6] Wang Z, Zhang X, Luo Y, et al. Therapeutic targeting of ARID1A-deficient cancer cells with RITA (Reactivating p53 and inducing tumor apoptosis). Cell Death Dis. 2024 May 29;15(5):375.
[7] Shin D, Kim EH, Lee J, et al. RITA plus 3-MA overcomes chemoresistance of head and neck cancer cells via dual inhibition of autophagy and antioxidant systems. Redox Biol. 2017 Oct;13:219-227.
[8] Azatyan A, Gallo-Oller G, Diao Y, et al. RITA downregulates Hedgehog-GLI in medulloblastoma and rhabdomyosarcoma via JNK-dependent but p53-independent mechanism. Cancer Lett. 2019 Feb 1;442:341-350.
RITA (NSC 652287)是一种三环噻吩衍生物，可结合p53dN（Kd=1.5nM）并阻断p53-HDM-2相互作用，抑制p53泛素化。RITA可用于多种癌症（如结直肠癌、肾癌、宫颈癌等）的相关研究[1-4]。
在体外，RITA（1-5μM）处理p53阳性肿瘤细胞（如HCT116、MCF-7等）16-24小时。在常氧和缺氧条件下，RITA显著诱导p53依赖性细胞凋亡，同时下调缺氧诱导因子1α（HIF-1α）和血管内皮生长因子（VEGF）的表达[5]。RITA（0.02–50μM）处理HCT116 ARID1A-/-细胞72小时。RITA显著诱导细胞凋亡，同时上调促凋亡基因PUMA和NOXA的表达并下调p21表达[6]。
在体内，RITA（10mg/kg；每天一次）腹腔注射，用于处理携带HN4-cisR头颈癌异种移植的BALB/c裸鼠，连续35天。RITA单独使用对肿瘤生长没有显著抑制作用，但与3-MA联合使用时显著抑制肿瘤生长[7]。RITA（10mg/kg；每天一次）腹腔注射于携带Rh36横纹肌肉瘤异种移植的NMRI-nu/nu裸鼠，连续20天。RITA显著抑制了横纹肌肉瘤异种移植肿瘤的生长[8]。
| Cell experiment [1]: | |
Cell lines | HCT116 p53+/+ and p53-/- colorectal cancer cells, MCF-7 breast cancer cells, MDA-MB-231 breast cancer cells, U2OS osteosarcoma cells, RCC4 renal carcinoma cells |
Preparation Method | Cells were maintained in Dulbecco's modified Eagle medium supplemented with 10% fetal calf serum. RITA (1-5μM) was dissolved in dimethyl sulfoxide (DMSO) and used to treat cells. |
Reaction Conditions | 1-5μM; 16-24 hours under normoxic (21% O₂) or hypoxic (1% O₂) conditions |
Applications | RITA induced p53-dependent apoptosis in normoxia and hypoxia, as indicated by increased sub-G₁ cell population and poly(ADP-ribose) polymerase (PARP) cleavage. RITA blocked hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression in a p53-dependent manner. RITA also induced phosphorylation of eukaryotic initiation factor 2α (eIF-2α) on Ser51 and downregulated p53 target proteins including HDM2 and p21. |
| Animal experiment [2]: | |
Animal models | NMRI-nu/nu nude mice (immunodeficient nude mice) |
Preparation Method | Rh36 rhabdomyosarcoma cells (3×10⁶ cells mixed with Matrigel) were injected subcutaneously into the right flank of mice. When tumor volume reached ≥0.150mL3, mice were treated with RITA (10mg/kg). |
Dosage form | 10mg/kg; i.p.; daily for 20 consecutive days |
Applications | RITA suppressed rhabdomyosarcoma xenograft tumor growth. |
References: | |
| Cas No. | 213261-59-7 | SDF | |
| 别名 | 5,5'-(2,5-呋喃二基)二-2-噻吩甲醇,NSC 652287 | ||
| 化学名 | [5-[5-[5-(hydroxymethyl)thiophen-2-yl]furan-2-yl]thiophen-2-yl]methanol | ||
| Canonical SMILES | C1=C(SC(=C1)C2=CC=C(O2)C3=CC=C(S3)CO)CO | ||
| 分子式 | C14H12O3S2 | 分子量 | 292.4 |
| 溶解度 | ≥ 14.6 mg/mL in DMSO, ≥ 9.84 mg/mL in EtOH with ultrasonic and warming | 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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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.42 mL | 17.0999 mL | 34.1997 mL |
| 5 mM | 684 μL | 3.42 mL | 6.8399 mL |
| 10 mM | 342 μL | 1.71 mL | 3.42 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。
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