MDV3100 (Enzalutamide)
(Synonyms: 恩杂鲁胺; MDV3100) 目录号 : GC12385
MDV3100(enzalutamide) 是第二代 AR 拮抗剂，在 LNCaP 前列腺细胞中的 IC50 为 36nM。
Cas No.:915087-33-1
Sample solution is provided at 25 µL, 10mM.
MDV3100(enzalutamide) is a second-generation AR antagonist with an IC50 of 36nM in LNCaP prostate cells[1,2]. MDV3100 could reduce androgen binding to AR, inhibit AR transport to the nucleus and prevent the binding of AR to androgen response elements[2].
MDV3100 combined with TKIs exerted a synergistic effect on a variety of PCa cells. MDV3100 combined with afatinib could suppress the proliferation and migration of 22RV1 cells, as well as cause their cell cycle arrest and apoptosis[2]. MDV3100 probed the bone microenvironment that led to stronger cancer cell adaptive responses and osteomimicry than bicalutamide. MDV3100 presented with better treatment response, in line with MDV3100 delaying time to bone-related events and MDV3100 extending survival in mCRPC[3]. MDV3100 promoted macrophage migration to PCa cells that consequently led to enhanced PCa cell invasion in human (C4-2B/THP1) and mouse (TRAMP-C1/RAW264.7) PCa cells–macrophages co-culture systems[4]
MDV3100 combination with KIF15 inhibitors significantly suppressed MDV3100-resistant PCa cell growth and xenograft progression. KIF15 inhibitors may enhance the sensitivity of prostate tumors to MDV3100 treatment, and rationalize a combination therapy of KIF15 inhibitors with MDV3100 to treat CRPC patients [5]. The antitumor efficacy of MDV3100 can be substantially improved by methylselenol prodrug, which also downregulates AR-FL and AR-Vs in vivo[6]. MDV3100 prolonged overall survival of metastatic CRPC patients who progressed after chemotherapy in a Phase III trial[7]
References:
[1]. Tran C, Ouk S, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009;324(5928):787-790.
[2]. Li J, Wu H, et al. Enhanced antitumor efficacy by combining afatinib with MDV3100 in castration-resistant prostate cancer. Pharmazie. 2022;77(2):59-66.
[3]. Bock N, Kryza T, et al. In vitro engineering of a bone metastases model allows for study of the effects of antiandrogen therapies in advanced prostate cancer. Sci Adv. 2021;7(27):eabg2564.
[4]. Lin TH, Izumi K, et al. Anti-androgen receptor ASC-J9 versus anti-androgens MDV3100 (Enzalutamide) or Casodex (Bicalutamide) leads to opposite effects on prostate cancer metastasis via differential modulation of macrophage infiltration and STAT3-CCL2 signaling. Cell Death Dis. 2013;4(8):e764.
[5]. Gao L, Zhang W, et al. KIF15-Mediated Stabilization of AR and AR-V7 Contributes to Enzalutamide Resistance in Prostate Cancer. Cancer Res. 2021;81(4):1026-1039.
[6]. Zhan Y, Cao B, et al. Methylselenol prodrug enhances MDV3100 efficacy for treatment of castration-resistant prostate cancer. Int J Cancer. 2013;133(9):2225-2233.
[7]. Scher HI, Fizazi K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367(13):1187-1197.
MDV3100(enzalutamide) 是第二代 AR 拮抗剂,在 LNCaP 前列腺细胞中的 IC50 为 36nM[1,2]。 MDV3100可减少雄激素与AR的结合,抑制AR向细胞核的转运,阻止AR与雄激素反应元件的结合[2]。
MDV3100 联合 TKIs 对多种 PCa 细胞产生协同作用。 MDV3100联合阿法替尼可抑制22RV1细胞的增殖和迁移,并引起细胞周期停滞和凋亡[2]。 MDV3100 探测了导致比比卡鲁胺更强的癌细胞适应性反应和骨拟态的骨微环境。 MDV3100 表现出更好的治疗反应,与 MDV3100 延迟骨骼相关事件的时间和 MDV3100 延长 mCRPC 的生存期[3] 一致。 MDV3100 促进巨噬细胞向 PCa 细胞迁移,从而导致增强 PCa 细胞在人 (C4-2B/THP1) 和小鼠 (TRAMP-C1/RAW264.7) PCa 细胞-巨噬细胞共培养系统中的侵袭[4]
MDV3100 与 KIF15 抑制剂的组合显着抑制了 MDV3100 抗性 PCa 细胞生长和异种移植进展。 KIF15 抑制剂可增强前列腺肿瘤对 MDV3100 治疗的敏感性,并合理化 KIF15 抑制剂与 MDV3100 联合治疗 CRPC 患者[5]。甲基硒醇前体药物可显着提高 MDV3100 的抗肿瘤功效,甲基硒醇前体药物还可在体内下调 AR-FL 和 AR-Vs[6]。在一项 III 期试验中,MDV3100 延长了化疗后进展的转移性 CRPC 患者的总生存期[7]
| Cell experiment [1]: | |
|
Cell lines |
LNCap, C4-2, PC3, DU145 and 22RV1 cell lines |
|
Preparation Method |
Different concentration gradients of various compounds (MDV3100， Afatinib, Erlotinib, Sorafenib, Gefitinib) were added to each group. The control group was treated with 0.1% DMSO. The cells were continuously treated for 72h, then supplemented with 10μL MTT solution for 4h. |
|
Reaction Conditions |
0-100μM |
|
Applications |
MDV3100 moderately inhibited the proliferation of PC3 and DU145 cells, both of which are androgen-independent PCa cell lines. Moreover, it also inhibited proliferation in the androgen-dependent LNCap, 22RV1 and C4-2 cell lines, with IC50 values of 1.74, 39.79 and 49.17μM, respectively. |
| Animal experiment [2]: | |
|
Animal models |
Male nude mice, Four-week-old |
|
Preparation Method |
6.0×106 C4-2B-ENZR cells, or 3.0×106 22Rv1 cells were injected subcutaneously into the mice. After the mice were surgically castrated, they were randomized into four groups (n=5/group) and treated as follows: (1) vehicle control (PBS, i.p.); (2) MDV3100 (10mg/kg, p.o.); (3) KIF15-IN-1 (10mg/kg, i.p.); (4) MDV3100 (10mg/kg, p.o.) + KIF15-IN-1 (10mg/kg, i.p.). Tumor tissues were harvested and weighed after 4 weeks of treatment. Tumor size was measured twice a week. |
|
Dosage form |
(1) vehicle control (PBS, i.p.); (2) MDV3100 (10mg/kg, p.o.); (3) KIF15-IN-1 (10mg/kg, i.p.); (4) MDV3100 (10mg/kg, p.o.) + KIF15-IN-1 (10mg/kg, i.p.)/p> |
|
Applications |
C4-2B-ENZR and 22Rv1 tumors treated with MDV3100 alone showed no difference to the control groups (MDV3100 vs. control; C4-2B-ENZR, 1145±119.3 vs. 1269±182mm3; 22Rv1, 1455±127.5 vs. 1547±97.93mm3). However, KIF15-IN-1 treatment reduced the tumor volume (C4-2B-ENZR, 633.5±85.3mm3; 22Rv1, 905.4±124.5mm3), and the combination of MDV3100 and KIF15-IN-1 induced further inhibition in tumor growth (C4-2B-ENZR,246.3±67.42mm3; 22Rv1, 481.5±87.82mm3). |
|
References: [1]. Li J, Wu H, et al. Enhanced antitumor efficacy by combining afatinib with MDV3100 in castration-resistant prostate cancer. Pharmazie. 2022;77(2):59-66. [2]. Gao L, Zhang W, et al. KIF15-Mediated Stabilization of AR and AR-V7 Contributes to Enzalutamide Resistance in Prostate Cancer. Cancer Res. 2021;81(4):1026-1039. |
|
| Cas No. | 915087-33-1 | SDF | |
| 别名 | 恩杂鲁胺; MDV3100 | ||
| 化学名 | 4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-fluoro-N-methylbenzamide | ||
| Canonical SMILES | CC1(C(=O)N(C(=S)N1C2=CC(=C(C=C2)C(=O)NC)F)C3=CC(=C(C=C3)C#N)C(F)(F)F)C | ||
| 分子式 | C21H16F4N4O2S | 分子量 | 464.4 |
| 溶解度 | ≥ 23.22mg/mL in DMSO | 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 | 2.1533 mL | 10.7666 mL | 21.5332 mL |
| 5 mM | 0.4307 mL | 2.1533 mL | 4.3066 mL |
| 10 mM | 0.2153 mL | 1.0767 mL | 2.1533 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
