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781661-94-7 (YM-155)

1

Identification

YM-155 YM-155
Name YM-155
Formula C20H19BrN4O3
MW 443.29
CAS No. 781661-94-7
EINECS
Smiles O=C1C2=C(C(C3=CC=CC=C31)=O)[N+](CC4=NC=CN=C4)=C(C)N2CCOC.[Br-]
Synonyms YM155; Sepantronium bromide;YM 155; 1-(2-methoxyethyl)-2-methyl-4,9-dioxo-3-(pyrazin-2-ylmethyl)-4,9-dihydro-1H-naphtho[2,3-d]imidazol-3-ium bromide
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
2

Introduction

YM155 (Sepantronium bromide) is a novel small molecule survivin suppressant with an IC50 of 0.54 nM for the inhibition of survivin promoter activity. IC50 Value: 0.54 nM Target: Survivin In vitro: YM155 is not sensitive to survivn gene promoter-driven luciferase reporter activity even at 30 μM.

Background Information

A small molecule survivin inhibitor which suppresses expression of survivin and induces apoptosis ......by AOBIOUS INC
YM155 (Sepantronium bromide) is a novel small molecule survivin suppressant with an IC50 of 0.54 nM for the inhibition of survivin promoter activity. YM155 also completely inhibited the growth of orthotopically xenografted PC-3 tumors. YM155 suppressed expression of survivin and induced apoptosis in PC-3 and PPC-1 human HRPC cell lines at 10 nmol/L. It selectively suppresses expression of survivin and induces apoptosis in p53-deficient cancer cells in vitro at 10 nM. YM155 is highly distributed to tumors and at concentrations approximately 20-fold higher than those in plasma. YM155 exerts anti-tumor effects in various in vivo cancer models, including prostate, pancreatic, and lung cancer. ......by AbMole BioScience
YM155 is a novel small molecule survivin suppressant with an IC50 of 0.54 nM for the inhibition of survivin promoter activity. ......by AdooQ BioScience, LLC
Description ......by Apexbio Technology LLC
Sepantronium, 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 ......by BOC Sciences
YM155 is a novel small molecule survivin suppressant; suppresses the expression of surviving and induces apoptosis in PC-3 and PPC-1 human HRPC cell lines at 10 nmol/L. ......by BioVision, Inc.,
Sepantronium bromide, also known as YM155, is a novel small molecule inhibitor of expression of the survivin protein, which itself is an inhibitor of apoptosis. Sepantronium bromide inhibited the the growth of various human cancer cell lines in vitro with GI50 values of 8.2 nM for null p53 PC-3, 2.3 nM for mutant p53 PPC-1, 4.0 nM for mutant p53 DU145, 8.2 nM for mutant p53 TSU-Prl, 11 nM for mutant p53 22Rvl hormone refractory prostate cancer cells; 4.2 nM for wt p53 SK-MEL-5, and 6.3 nM for wt p53 A375 malignant melanoma. Sepantronium bromide also induced extensive regression of xenografted PC-3 tumors in mice. Nakahara, T., et al. "YM155, a novel small-molecule survivin suppressant, induces regression of established human hormone-refractory prostate tumor xenografts." Cancer Res. 67: 8014-8021 (2007). Sepantronium bromide sensitized human non-small cell lung cancer (NSCLC) cells to γ-radiation both in vitro and in vivo. Iwasa, T., et al. "Radiosensitizing effect of YM155, a novel small-molecule survivin suppressant, in non-small cell lung cancer cell lines." Clin. Cancer Res. 14: 6496-6504 (2008). The uptake of [14C]sepantronium bromide into PC-3, lung cancer (Calu-6 and NCI-H358), malignant melanoma (A375 and SK-MEL-5), and non-Hodgkin's lymphoma (RL and Ramos) cell lines was dependent on incubation time, temperature, and drug concentration. Sepantronium bromide was taken up into these different cancer cells in a carrier-mediated manner and with a similar affinity (Km = 0.189-0.367 µM). Minematsu, T., et al. "Carrier-mediated uptake of 1-(2-methoxyethyl)-2-methyl-4,9-dioxo-3-(pyrazin-2-ylmethyl)-4,9-dihydro-1H-naphtho[2,3-d]imidazolium bromide (YM155 monobromide), a novel small-molecule survivin suppressant, into human solid tumor and lymphoma cells." Drug Metab. Dispos. 37: 619-628 (2009). Sepantronium bromide blocked the growth of 119 human cancer cell lines, with the greatest inhibition in lines derived from non-Hodgkin's lymphoma, hormone-refractory prostate cancer, ovarian cancer, sarcoma, non-small-cell lung cancer, breast cancer, leukemia and melanoma with an average GI50 of 15 nM. Sepantronium bromide inhibited the growth of tumor cell lines regardless of their p53 status and demonstrated significant antitumor activity in 5 various mice xenograft models without showing significant bodyweight loss. It also caused tumor regressions in vivo, possibly by its effects in reducing intratumoral survivin expression levels, increasing apoptosis and decreasing mitotic indices. Nakahara, T., et al. "Broad spectrum and potent antitumor activities of YM155, a novel small-molecule survivin suppressant, in a wide variety of human cancer cell lines and xenograft models." Cancer Sci. 102: 614-621 (2011). Sepantronium bromide demonstrated modest single-agent activity in patients with refractory and advanced non-small-cell lung cancer (NSCLC) in a multicenter phase II trial. A favorable safety/tolerability profile for sepantronium bromide was reported. Giaccone, G., et al. "Multicenter phase II trial of YM155, a small-molecule suppressor of survivin, in patients with advanced, refractory, non-small-cell lung cancer." J. Clin. Oncol. 27: 4481-4486 (2009). Sepantronium bromide induced autophagy-dependent apoptosis in prostate cancer cells. Wang, Q., et al. "Induction of autophagy-dependent apoptosis by the survivin suppressant YM155 in prostate cancer cells." Cancer Lett. 302: 29-36 (2011). Sepantronium bromide induced spontaneous apoptosis of melanoma cells, possibly by inhibiting survivin. It also demonstrated antiproliferative effects at nanomolar levels and caused tumor regression in established melanoma xenograft models. Yamanaka, K., et al. "Antitumor Activity of YM155, a Selective Small-Molecule Survivin Suppressant, Alone and in Combination with Docetaxel in Human Malignant Melanoma Models." Clin. Cancer Res. 17: 5423-5431 (2011). Sepantronium bromide induced decreased cellular proliferation and spontaneous apoptosis of human metastatic triple negative breast cancer cells (TNBC, with negative expression of estrogen and progesterone receptors and no overexpression of HER2/neu (ErbB-2)). In a preclinical TNBC mouse xenograft model, continuous treatment with sepantronium bromide caused the complete regression of subcutaneously established tumors. This compound inhibited spontaneous metastases and significantly improved the survival of animals bearing established metastatic tumors. Yamanaka, K., et al. "YM155, a selective survivin suppressant, inhibits tumor spread and prolongs survival in a spontaneous metastatic model of human triple negative breast cancer." Int. J. Oncol. 39: 569-575 (2011). A phase II clinical trial showed that sepantronium bromide had modest activity in taxane-pretreated castration-resistant prostate cancer (CRPC) and was also well tolerated. Tolcher, A.W., et al. "A phase II study of YM155, a novel small-molecule suppressor of survivin, in castration-resistant taxane-pretreated prostate cancer." Ann. Oncol. Aug 22 (2011) [Epub ahead of print]. ......by LC Laboratoies
YM-155 is a novel survivin suppressant with an IC50 of 0.54 nM for the inhibition of survivin promoter activity. ......by MedChemexpress Co., Ltd.
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. ......by MedKoo Biosciences, Inc.
A potent, specific survivin inhibitor that inhibits survivin promoter activity with IC50 of 0.54 nM; does not significantly inhibit SV40 promoter activity (>30 uM); suppresses expression of survivin and induces apoptosis in PC-3 and PPC-1 human HRPC cell lines at 10 nM, without effect on IAP- or Bcl-2-related proteins; induces massive tumor regression in PC-3 tumor mice model (3-10 mg/kg).Blood CancerPhase 1 Discontinued ......by ProbeChem
YM155 (Sepantronium Bromide) is a potent survivin suppressant by inhibiting Survivin promoter activity with IC50 of 0.54 nM in HeLa-SURP-luc and CHO-SV40-luc cells; does not significantly inhibit SV40 promoter activity, but is observed to slightly inhibit the interaction of Survivin with XIAP. Phase 2. ......by Selleck Chemicals LLC
YM155 (Sepantronium bromide) is a novel small molecule survivin suppressant with an IC50 of 0.54 nM for the inhibition of survivin promoter activity. ......by Target Molecule Corp.
3

Protocol(Only for Reference)

Cell Experiment

Cell lines PC-3 and PPC-1 cells
Conditions 1 μM, 48 hours
Method In both cell lines, YM155, at concentrations from 10 to 1000 nM, significantly decreased the viability of cells in a dose-dependent manner. When exposed to YM155, PC-3 and PPC-1 showed a concomitant increase in caspase-3 activity. These results suggest that YM155 induces apoptosis in human HRPC cells.
Source Apexbio Technology LLC
Cell lines Hormone refractory prostate cancer cell lines (PC-3, PPC-1, DU145, TSU-Pr1 and 22Rv1) and malignant melanoma cell lines (SK-MEL-5 and A375)
Conditions ~ 100 nM; 48 hours
Method Cells are seeded in 96-well plates at a density of 5-40 × 103. YM155 is dissolved in DMSO and added to cells for 48 hours. Then the cell count is determined by sulforhodamine B assay.
Source Selleck Chemicals LLC

Animal Experiment

Animal Models BALB/c nu/nu mice injected with PC-3 cells
Dosage Form Subcutaneous injection, 10 mg/kg
Applications Mice with large established s.c. xenografted PC-3 tumors received a 3-day continuous infusion of YM155 at 10 mg/kg. Saline control animals showed rapid tumor growth from day 0 (366 mm3) to day 7 (1,123 mm3), with no change in intratumoral surviving and actin protein levels. In contrast, animals treated with YM155 showed tumor regression from day 0 (292 mm3) to day7 (162 mm3), and a clear decrease in intratumoral survivin levels on days 3 and 7 was observed.
Source Apexbio Technology LLC
Animal Models PC-3 s.c. (orthotopic) xenografts in male nude mice (BALB/c nu/nu)
Dosage 5 mg/kg
Formulation Dissolved and diluted in saline immediately before administration
Administration Subcutaneous injection as a 3-day continuous infusion per week for 3 weeks by an implanted micro-osmotic pump
Source Selleck Chemicals LLC
4

Physical and Chemical Properties

Appearance:Light yellow to yellow solid EBNumber:EB000028830

Storage condition

Store at -20°C by Apexbio Technology LLC
Store at or below -20 oC. by LC Laboratoies

Solubility

Soluble in DMSO > 10 mM by Apexbio Technology LLC
Soluble in DMSO. by LC Laboratoies
DMSO ≥85mg/mL Water ≥85mg/mL Ethanol ≥20mg/mL by MedChemexpress Co., Ltd.
(25°C) * In vitro DMSO 55 mg/mL (124.07 mM); Water89 mg/mL (200.77 mM); Ethanol6 mg/mL (13.53 mM); In vivo Saline30 mg/mL by Selleck Chemicals LLC
5

Mechanism and Indication

6

Clinical Information

Product Name Sponsor & Collaborators Indications Start Date End Date Phase
YM-155 Astellas Pharma Inc Metastatic breast cancer 2009/12/31 2013/6/30 Phase 2 Clinical
YM-155 Astellas Pharma Inc Stage III melanoma 2009/11/30 2012/8/31 Phase 2 Clinical
YM-155 Astellas Pharma Inc Stage IV melanoma 2009/11/30 2012/8/31 Phase 2 Clinical
YM-155 Astellas Pharma Inc Non-Hodgkin lymphoma 2009/11/30 2013/8/31 Phase 2 Clinical
YM-155 Astellas Pharma Inc Non-small-cell lung cancer 2006/12/31 2007/3/31 Phase 2 Clinical
YM-155 - Phase 2
7

Safety Data of YM-155

8

Spectral Information

9

Suppliers List

Company Price and Availability Country/Region
AOBIOUS INC 1mg/USD15() USA
AbMole BioScience USA
AdooQ BioScience, LLC USA
Apexbio Technology LLC USA
Ark Pharm, Inc. USA
BOC Sciences
BioVision, Inc., USA
Biochempartner Co., Ltd China
CHEMSCENE, LLC 5mg/USD60();10mg/USD84() USA
Cayman Chemical Company USA
LC Laboratoies USA
MedChemexpress Co., Ltd. 5mg/USD60();10mg/USD84() USA
MedKoo Biosciences, Inc. USA
ProbeChem
Selleck Chemicals LLC 5mg/USD70(In stock);10mM/1mLIn DMSO/USD112(In stock);10mg/USD120(In stock);25mg/USD270(In stock);100mg/USD770(In stock) USA
Shanghai Haoyuan Chemexpress Co., Ltd. 5mg/USD60();10mg/USD84() China
Target Molecule Corp. 10mg/USD67();25mg/USD132();50mg/USD234() USA
10

Related Products

Other Forms of 781661-94-7

Name CAS No Formula MW
YM-155 (hydrochloride) 355406-09-6 C20H19ClN4O3 398.84
LTX-401 (trifluoroacetate) 1262851-71-7 C27H35F6N3O5 595.57
LTX-401 1398051-86-9 C23H35N3O 369.54
Carboxyspermidine 64817-93-2 C8H21Cl2N3O2 262.18
SMI-16a 587852-28-6 C13H13NO3S 263.31
AS-35 108427-72-1 C21H20N6O4 420.42
A-69412 123606-23-5 C7H10N2O3 170.17
Iralukast 151581-24-7 C38H37F3O8S 710.76
LY 345899 10538-99-5 C20H21N7O7 471.42
CM-4620 1713240-67-5 C19H11ClF3N3O3 421.76
SNS-062 1270014-40-8 C19H21ClN6O 384.86
8-epidiosbulbin E acetate 91095-48-6 C21H24O7 388.41

Recommended Compounds in Survivin Autophagy

Name CAS No Formula MW
YM-155 (hydrochloride) 355406-09-6 C20H19ClN4O3 398.84
Pirarubicin (Hydrochloride) 95343-20-7 C32H38ClNO12 664.1
Berberine (chloride) 633-65-8 C20H18ClNO4 371.8142
DMH-1 1206711-16-1 C24H20N4O 380.44
CB-839 1439399-58-2 C26H24F3N7O3S 571.57
H-89 (dihydrochloride) 130964-39-5 C20H22BrCl2N3O2S 519.2826
Shikonin 517-89-5 C16H16O5 288.3
H 89 127243-85-0 C20H20BrN3O2S 446.36
Eupatilin 22368-21-4 C18H16O7 344.32
Isoalantolactone 470-17-7 C15H20O2 232.32
Scutellarein 529-53-3 C15H10O6 286.24
Leonurine 24697-74-3 C14H21N3O5 311.33
Berbamine (dihydrochloride) 6078-17-7 C37H42Cl2N2O6 681.6452
Ruxolitinib (S enantiomer) 941685-37-6 C17H18N6 306.37
D-Glucosamine (Hydrochloride) 66-84-2 C6H14ClNO5 215.63
Schizandrin A 61281-38-7 C22H28O6 388.45
Schisandrol B 58546-54-6 C23H28O7 416.46
Schisandrol A 7432-28-2 C24H32O7 432.51
Icaritin 118525-40-9 C21H20O6 368.3799
Bicyclol 118159-48-1 C19H18O9 390.34

Recommended Compounds in Same Indication

Name CAS No Formula MW
CAL-101 870281-82-6 C22H18FN7O 415.42
Trametinib 871700-17-3 C26H23FIN5O4 615.39
PU-H71 873436-91-0 C18H21IN6O2S 512.37
Crizotinib 877399-52-5 C21H22Cl2FN5O 450.34
Ostarine 841205-47-8 C19H14F3N3O3 389.33
AT9283 896466-04-9 C19H23N7O2 381.43
AT-101 90141-22-3 C30H30O8 518.55
IDO5L 914471-09-3 C9H7ClFN5O2 271.6356
Dovitinib 405169-16-6 C21H21FN6O 392.43
SB-590885 405554-55-4 C27H27N5O2 453.54
MK-0752 471905-41-6 C21H21ClF2O4S 442.9
Cyclophosphamide 50-18-0 C7H15Cl2N2O2P 261.09
N-Hydroxy-3-(3-phenylsulfamoylphenyl)acrylamide 414864-00-9 C15H14N2O4S 318.34766
Retaspimycin 857402-23-4 C31H45N3O8 587.7
Retaspimycin (Hydrochloride) 857402-63-2 C31H46ClN3O8 624.17
Motesanib (Diphosphate) 857876-30-3 C22H29N5O9P2 569.44
Anamorelin (hydrochloride) 861998-00-7 C31H43ClN6O3 583.16
Litronesib 910634-41-2 C23H37N5O4S2 511.701
LY2603618 911222-45-2 C18H22BrN5O3 436.3
AT13387 912999-49-6 C24H31N3O3 409.52
11

Route of Synthesis

12

References

[1]. Iwasa, Tsutomu; Okamoto, Isamu; Suzuki, Minoru; Radiosensitizing Effect of YM155, a Novel Small-Molecule Survivin Suppressant, in Non-Small Cell Lung Cancer Cell Lines. Clinical Cancer Research (2008), 14(20), 6496-6504

[2]. Satoh, Taroh; Okamoto, Isamu; Miyazaki, Masaki; Morinaga, Ryotaroh; Phase I Study of YM155, a Novel Survivin Suppressant, in Patients with Advanced Solid Tumors. Clinical Cancer Research (2009), 15(11), 3872-3880.

[3]. Aoyama Y, Kaibara A, Takada A, Nishimura T, Katashima M, Sawamoto T.Population pharmacokinetic modeling of Sepantronium bromide (YM155), a small molecule survivin suppressant, in patients with non-small cell lung cancer, hormone refractory prostate cancer, or unresectable stage III or IV melanoma.Invest New Drugs. 2012 Aug 16.

[4]. Yamauchi T, Nakamura N, Hiramoto M, Yuri M, Yokota H, Naitou M, Takeuchi M, Yamanaka K, Kita A, Nakahara T, Kinoyama I, Matsuhisa A, Kaneko N, Koutoku H, Sasamata M, Kobori M, Katou M, Tawara S, Kawabata S, Furuichi K.Sepantronium Bromide (YM155) induces disruption of the ILF3/p54(nrb) complex, which is required for survivin expression.Biochem Biophys Res Commun. 2012 Sep 7;425(4):711-6. Epub 2012 Jul 27.

[5]. Aoyama Y, Nishimura T, Sawamoto T, Satoh T, Katashima M, Nakagawa K.Pharmacokinetics of sepantronium bromide (YM155), a small-molecule suppressor of survivin, in Japanese patients with advanced solid tumors: dose proportionality and influence of renal impairment.Cancer Chemother Pharmacol. 2012 Sep;70(3):373-80. Epub 2012 Jul 18.

Protocol Reference

[1] Nakahara T, Takeuchi M, Kinoyama I, et al. YM155, a novel small-molecule survivin suppressant, induces regression of established human hormone-refractory prostate tumor xenografts. Cancer research, 2007, 67(17): 8014-8021.

......by Apexbio Technology LLC
13

More Information

YM-155

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