YM-155, a survivin inhibitor.

YM-155 is a novel survivin suppressant with an IC50 of 0.54 nM for the inhibition of survivin promoter activity. Sepantronium bromide, also known as YM-155, is a small-molecule proapoptotic agent with potential antineoplastic activity. Survivin inhibitor YM155 selectively inhibits survivin expression in tumor cells, resulting in inhibition of survivin antiapoptotic activity (via the extrinsic or intrinsic apoptotic pathways) and tumor cell apoptosis. Survivin, a member of the inhibitor of apoptosis (IAP) gene family, is expressed during embryonal development and is absent in most normal, terminally differentiated tissues; upregulated in a variety of human cancers, its expression in tumors is associated with a more aggressive phenotype, shorter survival times, and a decreased response to chemotherapy.

Product information

CAS Number: 781661-94-7

Molecular Weight: 443.29

Formula: C20H19BrN4O3

Synonym:

Sepantronium bromide

YM 155

YM155

YM-155

Chemical Name: 3-(2-methoxyethyl)-2-methyl-4, 9-dioxo-1-(pyrazin-2-ylmethyl)-4, 9-dihydro-1H-naphtho[2, 3-d]imidazol-3-ium bromide

Smiles: [Br-].CC1N(CC2=CN=CC=N2)C2=C(C(=O)C3=CC=CC=C3C2=O)[N+]=1CCOC

InChiKey: QBIYUDDJPRGKNJ-UHFFFAOYSA-M

InChi: InChI=1S/C20H19N4O3.BrH/c1-13-23(9-10-27-2)17-18(24(13)12-14-11-21-7-8-22-14)20(26)16-6-4-3-5-15(16)19(17)25;/h3-8,11H,9-10,12H2,1-2H3;1H/q+1;/p-1

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 10.66 mg/mL

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

YM155 is not sensitive to survivn gene promoter-driven luciferase reporter activity even at 30 μM. YM155 significantly inhibits endogenous survivin expression in PC-3 and PPC-1 human HRPC cells with deficient p53 through transcriptional inhibition of the survivin gene promoter. On the contrary YM155 shows no sufficient effect on protein expression of c-IAP2, XIAP, Bcl-2, Bcl-xL, Bad, α-actin, and β-tubulin at 100 nM. YM155 indicates great apoptosis in human cancer cell lines including PC-3 and PPC-1 with a concomitant increase in caspase-3 activity. YM155 potently inhibits human cancer cell lines (mutated or truncated p53) including PC-3, PPC-1, DU145, TSU-Pr1, 22Rv1, SK-MEL-5 and A375 with IC50 from 2.3 to 11 nM, respectively[1]. YM155 increases the sensitivity of NSCLC cells to γ-radiation. The combination of YM155 and γ-radiation increases both the number of apoptotic cells and the activity of caspase-3. YM155 delays the repair of radiation-induced double-strand breaks in nuclear DNA.

In Vivo:

YM155 completely inhibits the tumor growth of PC-3 s.c. xenografted prostate tumors at doses of 3 and 10 mg/kg, without body weight loss and blood cell count decrease. Pharmacokinetic analysis shows that YM155 is highly distributed to tumor tissue. Moreover, YM155 shows 80% TGI at a dose of 5 mg/kg in PC-3 orthotopic xenografts[1]. The combination therapy with YM155 and γ-radiation shows great antitumor activity against H460 or Calu6 xenografts in nude mice[2]. In this orthotopic renal and metastatic lung tumors models, YM155 and IL-2 additively decreases tumor weight, lung metastasis, and luciferin-stained tumor images.

References:

1. Nakahara T, et al. YM155, a novel small-molecule survivin suppressant, induces regression of established human hormone-refractory prostate tumor xenografts. Cancer Res. 2007 Sep 1;67(17):8014-21.
2. Iisa T, et al. Radiosensitizing effect of YM155, a novel small-molecule survivin suppressant, in non-small cell lung cancer cell lines. Clin Cancer Res. 2008 Oct 15;14(20):6496-504.
3. Guo K, et al. A combination of YM-155, a small molecule survivin inhibitor, and IL-2 potently suppresses renal cell carcinoma in murine model. Oncotarget. 2015 Aug 28;6(25):21137-47.

Products are for research use only. Not for human use.