GANT61
(Synonyms: 2,2'-[[二氢-2-(4-吡啶基)-1,3(2H,4H)-嘧啶二基]二(亚甲基)]二[N,N-二甲基苯胺],NSC 136476) 目录号 : GC10359
GANT61 能够有效阻断 GLI1 和 GLI2 诱导的转录，IC50 为 5 μM。
Cas No.:500579-04-4
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
GANT61 was able to efficiently block GLI1 as well as GLI2-induced transcription, IC50 is 5 μM[1].
Incubated with GANT61 (5 μM ;48 h) in PANC1 or 22Rv1 cells, the expression of GLI1 and PTCH was decreased[1]. In the Hh-responsive murine cell line C3H/10T1/2cell line, GANT61 (5/10μM ;48 h) dose-dependently suppressed endogenous Glil transcriptional upregulation induced by SHH treatment [2]. GANT61 treatment (20μM ;36h) abolished the clonogenicity of all six human colon carcinoma cell lines. Analysis of the molecular mechanisms of GANT61-induced cytotoxicity in HT29 cells showed increased Fas expression and decreased expression of PDGFRα[3]. GANT61 induced transient cellular accumulation at G(1)-S (24 hours) and in early S-phase (32 hours), with elevated p21(Cip1), cyclin E, and cyclin A in HT29 cells. GANT61 induced DNA damage within 24 hours, with the appearance of p-ATM and p-Chk2[4]. GANT61 induces cell death of SK-N-LO cells in a caspase-independent manner, by inhibiting DNA replication in the S phase[7]. GANT61 caused growth arrest and apoptosis in AML cells. Synergism effect between GANT61 and rapamycin was found in Kasumi-1, HL-60 and U937 cell lines[5].
GANT61(50 mg/kg; s.c.;16 days) induced tumor growth regression until no tumor was palpable in Human prostate cancer xenograft[1].GANT61(50 mg/kg; i.g. 12 days) enhanced the effects of chemotherapeutic drugs used in the treatment of neuroblastoma in an additive or synergistic manner and reduced the growth of established neuroblastoma xenografts in nude mice[6].
References:
[1]. Lauth M, Bergstr?m A,et,al. Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists. Proc Natl Acad Sci U S A. 2007 May 15;104(20):8455-60. doi: 10.1073/pnas.0609699104. Epub 2007 May 9. PMID: 17494766; PMCID: PMC1866313.
[2]. Desch P, Asslaber D et,al.Inhibition of GLI, but not Smoothened, induces apoptosis in chronic lymphocytic leukemia cells. Oncogene. 2010 Sep 2;29(35):4885-95. doi: 10.1038/onc.2010.243. Epub 2010 Jul 5. PMID: 20603613.
[3]. Mazumdar T, DeVecchio J, et,al.Hedgehog signaling drives cellular survival in human colon carcinoma cells. Cancer Res. 2011 Feb 1;71(3):1092-102. doi: 10.1158/0008-5472.CAN-10-2315. Epub 2010 Dec 6. PMID: 21135115; PMCID: PMC3032813.
[4]. Mazumdar T, Devecchio J, et,al. Blocking Hedgehog survival signaling at the level of the GLI genes induces DNA damage and extensive cell death in human colon carcinoma cells. Cancer Res. 2011 Sep 1;71(17):5904-14. doi: 10.1158/0008-5472.CAN-10-4173. Epub 2011 Jul 11. PMID: 21747117; PMCID: PMC3165104.
[5]. Pan D, Li Y et,al. Gli inhibitor GANT61 causes apoptosis in myeloid leukemia cells and acts in synergy with rapamycin. Leuk Res. 2012 Jun;36(6):742-8. doi: 10.1016/j.leukres.2012.02.012. Epub 2012 Mar 6. PMID: 22398221.
[6]. Wickstr?m M, Dyberg C, et,al.Targeting the hedgehog signal transduction pathway at the level of GLI inhibits neuroblastoma cell growth in vitro and in vivo. Int J Cancer. 2013 Apr 1;132(7):1516-24. doi: 10.1002/ijc.27820. Epub 2012 Oct 3. PMID: 22949014.
[7]. Matsumoto T, Tabata K, et,al.The GANT61, a GLI inhibitor, induces caspase-independent apoptosis of SK-N-LO cells. Biol Pharm Bull. 2014;37(4):633-41. doi: 10.1248/bpb.b13-00920. PMID: 24694609.
GANT61 能够有效阻断 GLI1 和 GLI2 诱导的转录，IC50 为 5 μM[1]。
在 PANC1 或 22Rv1 细胞中与 GANT61 (5 μM ;48 h) 孵育后，GLI1 和 PTCH 的表达降低[1]。在 Hh 反应性小鼠细胞系 C3H/10T1/2 细胞系中，GANT61 (5/10μM ;48 h) 剂量依赖性地抑制由 SHH 处理诱导的内源性 Glil 转录上调 [2]。 GANT61 处理（20μM；36 小时）消除了所有六种人结肠癌细胞系的克隆形成。 GANT61 诱导 HT29 细胞毒性的分子机制分析表明，Fas 表达增加，PDGFRα 表达减少[3]。 GANT61 在 G(1)-S（24 小时）和早期 S 期（32 小时）诱导瞬时细胞积累，在 HT29 细胞中 p21(Cip1)、细胞周期蛋白 E 和细胞周期蛋白 A 升高。 GANT61 在 24 小时内诱导 DNA 损伤，并出现 p-ATM 和 p-Chk2[4]。 GANT61 通过抑制 S 期 DNA 复制，以不依赖半胱天冬酶的方式诱导 SK-N-LO 细胞死亡[7]。 GANT61 在 AML 细胞中引起生长停滞和细胞凋亡。在Kasumi-1、HL-60和U937细胞系[5]中发现GANT61与雷帕霉素有协同作用。
GANT61（50 mg/kg；皮下注射；16 天）诱导肿瘤生长消退，直到在人前列腺癌异种移植物中未触及肿瘤[1]。GANT61（50 mg/kg；即 12 天） )以相加或协同的方式增强化疗药物治疗神经母细胞瘤的作用，降低已建立的裸鼠神经母细胞瘤异种移植物的生长[6]。
| Compound Screen [1]: | |
|
Preparation Method |
HEK293 cells were transfected with GLI1 expression plasmid, together with the reporter plasmids 12xGliBS-Luc and R-Luc on 10-cm plates (day 0). Twenty-four hours later, cells were seeded in white 96-well plates with clear bottom at a density of 15,000 cells per well. Cells were allowed to attach, and compounds (1990 compounds) were added at a final concentration of 10 μM in DMSO (0.5% final DMSO concentration) (day 1.5). Cells were grown for another 24 h, subsequently lysed, and then analyzed by using the Dual Luciferase kit. Plates were read on a Berthold Technologies microplate luminometer. |
|
Applications |
GANT61 was able to efficiently block GLI1 as well as GLI2-induced transcription, IC50 is 5 μM. |
| Cell experiment [1]: | |
|
Cell lines |
PANC1 and 22Rv1 cells |
|
Preparation Method |
PANC1 and 22Rv1 cells were treated with 5 μM GANT61 for 48 h. |
|
Reaction Conditions |
5 μM GANT61; 48 h |
|
Applications |
Incubation of PANC1 or 22Rv1 cells with 5 μM GANT61 for 48 h led to a reduction in GLI1 and PTCH expression. |
| Animal experiment [1]: | |
|
Animal models |
Female BALB/c nude mice (nu/nu). |
|
Preparation Method |
22Rv1 cells suspension was injected s.c. at the posterior flank of female BALB/c nude mice (nu/nu). Animals were randomly divided into four groups (n = 4 5) and treated with solvent only (corn oil:ethanol, 4:1) or GANT61 (50 mg/kg) for 16 days. s.c. injections of compounds were performed several centimeters away from the tumor. |
|
Dosage form |
50 mg/kg GANT61;16 days . (s.c. injections of compounds were performed several centimeters away from the tumor.) |
|
Applications |
GANT61 induced growth regression until no tumor was palpable. |
|
References: [1]. Lauth M, Bergström A, et,al.Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists. Proc Natl Acad Sci U S A. 2007 May 15;104(20):8455-60. doi: 10.1073/pnas.0609699104. Epub 2007 May 9. PMID: 17494766; PMCID: PMC1866313. |
|
| Cas No. | 500579-04-4 | SDF | |
| 别名 | 2,2'-[[二氢-2-(4-吡啶基)-1,3(2H,4H)-嘧啶二基]二(亚甲基)]二[N,N-二甲基苯胺],NSC 136476 | ||
| 化学名 | 2-[[3-[[2-(dimethylamino)phenyl]methyl]-2-pyridin-4-yl-1,3-diazinan-1-yl]methyl]-N,N-dimethylaniline | ||
| Canonical SMILES | CN(C)C1=CC=CC=C1CN2CCCN(C2C3=CC=NC=C3)CC4=CC=CC=C4N(C)C | ||
| 分子式 | C27H35N5 | 分子量 | 429.6 |
| 溶解度 | ≥ 9.95mg/mL in Ethanol | 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 | 2.3277 mL | 11.6387 mL | 23.2775 mL |
| 5 mM | 0.4655 mL | 2.3277 mL | 4.6555 mL |
| 10 mM | 0.2328 mL | 1.1639 mL | 2.3277 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