BTdCPU
目录号 : GC38467
BTdCPU是一种通过激活血红素调节抑制激酶（HRI）发挥作用的化合物，BTdCPU能够促进eIF2α的磷酸化，诱导细胞凋亡。
Cas No.:1257423-87-2
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');)
BTdCPU is a compound that exerts its function by activating the heme-regulated inhibitor (HRI) kinase. BTdCPU promotes the phosphorylation of eIF2α and induces cellular apoptosis[1-2]. BTdCPU holds potential in cancer research, particularly for the study of multiple myeloma and its drug-resistant subtypes[3-4].
In vitro, treatment of multiple myeloma cell lines (MM1.S, H929, MM1.R, RPMI8266, U266) and primary CD138+ cells derived from multiple myeloma patients with BTdCPU (10-20μM) for 4 or 48 hours activated the HRI kinase, induced phosphorylation of eIF2α, upregulated the expression of the pro-apoptotic protein CHOP, and triggered apoptosis[5]. When HEK293T cells, SHSY5Y cells, and Perk+/+ and Perk-/- MEFs were treated with BTdCPU (10μM) for 3 hours, BTdCPU induced mitochondrial membrane depolarization, activated the OMA1-DELE1-HRI mitochondrial stress signaling axis, led to mitochondrial fragmentation, and reduced ATP-linked respiration. This mitochondrial depolarization occurred independently of the integrated stress response (ISR) signaling[6].
In vivo, in a C57BL/6 leukemia mouse model bearing BCR-ABL+ B-ALL cells, intraperitoneal administration of BTdCPU (400mg/kg/day) combined with oral ABT-263 (100mg/kg/day) for 14 consecutive days (starting from day 5 post-transplantation), BTdCPU significantly prolonged the survival of leukemic mice, reduced peripheral white blood cell counts, suppressed MCL-1 protein expression, and upregulated ATF4 levels in the bone marrow[7]. In female nude mice carrying MCF-7 human breast cancer xenografts, intraperitoneal administration of BTdCPU (175mg/kg/day) for 21 consecutive days (starting from tumor transplantation), BTdCPU significantly inhibited tumor growth, induced complete tumor stasis, upregulated phosphorylated eIF2α protein levels in tumor tissues, and did not cause significant hematological toxicity or organ pathological damage[8].
References:
[1] Blázquez AB, Martín-Acebes MA, Poderoso T, et al. Relevance of oxidative stress in inhibition of eIF2 alpha phosphorylation and stress granules formation during Usutu virus infection. PLoS Negl Trop Dis. 2021 Jan 25;15(1):e0009072.
[2] Cuoco CA, Ren W, Baron KR, et al. Pharmacological targeting of RIG-I can selectively activate the integrated stress response. Sci Adv. 2025 Oct 31;11(44):eadt3014.
[3] Zhang C, Xu H, Tang Q, et al. CaMKII suppresses proteotoxicity by phosphorylating BAG3 in response to proteasomal dysfunction. EMBO Rep. 2024 Oct;25(10):4488-4514.
[4] Ogami K, Richard P, Chen Y, et al. An Mtr4/ZFC3H1 complex facilitates turnover of unstable nuclear RNAs to prevent their cytoplasmic transport and global translational repression. Genes Dev. 2017 Jun 15;31(12):1257-1271.
[5] Burwick N, Zhang MY, de la Puente P, et al. The eIF2-alpha kinase HRI is a novel therapeutic target in multiple myeloma. Leuk Res. 2017 Apr;55:23-32.
[6] Perea V, Baron KR, Dolina V, et al. Pharmacologic Activation of a Compensatory Integrated Stress Response Kinase Promotes Mitochondrial Remodeling in PERK-deficient Cells. bioRxiv [Preprint]. 2023 May 17:2023.03.11.532186.
[7] Smith KH, Budhraja A, Lynch J, et al. The Heme-Regulated Inhibitor Pathway Modulates Susceptibility of Poor Prognosis B-Lineage Acute Leukemia to BH3-Mimetics. Mol Cancer Res. 2021 Apr;19(4):636-650.
[8] Chen T, Ozel D, Qiao Y, et al. Chemical genetics identify eIF2α kinase heme-regulated inhibitor as an anticancer target. Nat Chem Biol. 2011 Jul 17;7(9):610-6.
BTdCPU是一种通过激活血红素调节抑制激酶（HRI）发挥作用的化合物，BTdCPU能够促进eIF2α的磷酸化，诱导细胞凋亡[1-2]。BTdCPU在癌症研究领域具有应用潜力，尤其适用于多发性骨髓瘤及其耐药亚型的研究[3-4]。
在体外，BTdCPU（10-20μM）处理多发性骨髓瘤细胞系（MM1.S、H929、MM1.R、RPMI8266、U266）和原代多发性骨髓瘤患者来源的CD138+细胞4小时或48小时，BTdCPU通过激活HRI激酶诱导eIF2α磷酸化，上调促凋亡蛋白CHOP的表达，并诱导细胞凋亡[5]。BTdCPU（10μM）处理HEK293T细胞、SHSY5Y细胞以及Perk+/+和Perk-/- MEFs 3小时，BTdCPU诱导线粒体膜电位去极化，激活OMA1-DELE1-HRI线粒体应激信号轴，导致线粒体碎片化，并降低ATP关联呼吸，但该线粒体去极化不依赖于整合应激反应（ISR）信号[6]。
在体内，BTdCPU（400mg/kg/day）腹腔注射处理携带BCR-ABL+ B-ALL细胞的C57/BL6白血病小模型（从移植后第5天开始，连续14天），BTdCPU与口服ABT-263（100mg/kg/day）联合治疗显著延长白血病小鼠的生存期，降低外周血白细胞计数，并诱导骨髓中MCL-1蛋白表达的抑制和ATF4的上调[7]。BTdCPU（175mg/kg/day）腹腔注射处理携带MCF-7人乳腺癌异种移植瘤的雌性裸鼠（从肿瘤移植后开始，连续21天），BTdCPU显著抑制肿瘤生长并诱导肿瘤完全停滞，同时上调肿瘤组织中磷酸化eIF2α蛋白表达水平，且未引起明显血液学毒性或器官病理损伤[8]。
| Cell experiment [1]: | |
Cell lines | Multiple myeloma cell lines (MM1.S, H929, MM1.R, RPMI8266, U266), primary CD138+ multiple myeloma cells from patients, and healthy donor bone marrow mononuclear cells |
Preparation Method | Cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS) at 37°C, 5% CO₂. Cells were treated with BTdCPU at concentrations ranging from 10 to 20μM for 4 to 48 hours. |
Reaction Conditions | 10–20μM; 4–48 hours |
Applications | BTdCPU activated the heme-regulated inhibitor (HRI) kinase, inducing phosphorylation of eIF2α and upregulating pro-apoptotic proteins CHOP and ATF4. BTdCPU significantly induced apoptosis in both dexamethasone-sensitive and-resistant multiple myeloma cells, with minimal toxicity to normal bone marrow cells. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice bearing BCR-ABL+ B-ALL leukemia cells. |
Preparation Method | Mice were intraperitoneally administered BTdCPU (400mg/kg/day) and orally administered ABT-263 (100mg/kg/day) for 14 consecutive days, starting 5 days after leukemia cell injection. Mice were monitored for survival and analyzed for leukemia burden and molecular changes. |
Dosage form | 400mg/kg/day; i.p.; Daily for 14 days. |
Applications | BTdCPU combined with ABT-263 significantly prolonged survival of leukemia-bearing mice, reduced peripheral white blood cell counts, and repressed MCL-1 protein expression while inducing ATF4 upregulation in bone marrow cells, demonstrating in vivo efficacy of HRI pathway activation in sensitizing leukemia to BH3-mimetic therapy. |
References: | |
| Cas No. | 1257423-87-2 | SDF | |
| Canonical SMILES | O=C(NC1=CC=C2N=NSC2=C1)NC3=CC=C(C(Cl)=C3)Cl | ||
| 分子式 | C13H8Cl2N4OS | 分子量 | 339.2 |
| 溶解度 | DMSO: ≥ 250 mg/mL (737.03 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 | 2.9481 mL | 14.7406 mL | 29.4811 mL |
| 5 mM | 589.6 μL | 2.9481 mL | 5.8962 mL |
| 10 mM | 294.8 μL | 1.4741 mL | 2.9481 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: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet