Delving into the Latest Updates on Sepantronium Bromide with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Sepantronium bromide (JAN/USAN), PC-002, YM-155

+ [1]

Target

survivin

Mechanism

survivin inhibitors(Baculoviral IAP repeat-containing protein 5 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [3]

Active Indication

C-Myc Rearrangement B-Cell LymphomaProstate Neuroendocrine CarcinomaBurkitt Lymphoma+ [2]

Inactive Indication

Advanced cancerAdvanced Lung Non-Small Cell CarcinomaB-cell lymphoma refractory+ [6]

Originator Organization

Astellas Pharma, Inc.

Active Organization

Haikou Kerui Hua Biotechnology Corporation Limited

Beijing Percans Oncology Co., Ltd.

Cothera Bioscience, Inc.

Inactive Organization

Astellas Pharma, Inc.

National Cancer Institute

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (US)

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Structure/Sequence

Molecular FormulaC20H19BrN4O3

InChIKeyQBIYUDDJPRGKNJ-UHFFFAOYSA-M

CAS Registry781661-94-7

Background:
Carboplatin-paclitaxel is a commonly used chemotherapy combination for advanced non-small-cell lung carcinoma (NSCLC) and other solid tumors. In a randomized clinical trial, the combination of carboplatin, paclitaxel, and the additional chemotherapy drug bevacizumab had a better response rate and survival compared to carboplatin and paclitaxel alone. However, this trial treated only patients with a specific diagnosis and treatment risks. Further research is needed to determine whether this combination is useful for other diagnoses.
YM155 is a drug that targets a type of chemical often found in cancer cells. It has been investigated in several phase I and phase II clinical trials, and it has been shown to be well tolerated and moderately effective in treating advanced NSCLC in patients who had not responded well to one or two standard treatments.
Objectives:
- To determine the efficacy of the combination of carboplatin, paclitaxel, and YM155 in the treatment of non-small-cell lung cancer.
Eligibility:
- Individuals 18 years of age and older who have been diagnosed with advanced non-small-cell lung carcinoma or other solid tumors for which standard therapy is not likely to be effective.
Design:
Before the start of the study, participants will be screened with a medical history, blood tests, imaging scans of the affected areas, tumor biopsies, and other tests as directed by the study doctors.
Participants will be treated for six 21-day cycles, or 18 weeks of treatment. Each cycle will include blood tests and imaging studies as required.
On day 1 of each cycle, participants will receive an infusion of paclitaxel and carboplatin, followed by a 4-day infusion of YM155 (through a portable electronic infusion pump).
Participants will have a computed tomography scan or other imaging every other cycle (approximately every 6 weeks) to determine whether the therapy is affecting the cancer site.
After the sixth cycle, participants will return for follow-up visits at least every 3 months, and will be asked to remain in contact with the researchers to allow further study of the long-term effects of the treatment.

Start Date01 Feb 2010

Sponsor / Collaborator

National Cancer Institute

NCT01038804

/ CompletedPhase 2

A Phase II, Multicenter, Open-Label, Randomized Study of YM155 Plus Docetaxel as First-Line Treatment in Subjects With HER2 Negative Metastatic Breast Cancer

The purpose of this study is to evaluate survival, response rate, safety and tolerability of YM155 given in combination with docetaxel as first-line treatment in subjects with human epidermal growth factor 2 non-overexpressing (HER2 negative) metastatic breast cancer.

Start Date01 Dec 2009

Sponsor / Collaborator

Astellas Pharma, Inc.

100 Clinical Results associated with Sepantronium Bromide

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100 Translational Medicine associated with Sepantronium Bromide

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100 Patents (Medical) associated with Sepantronium Bromide

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530

Literatures (Medical) associated with Sepantronium Bromide

01 Mar 2025·BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

Single-cell RNA sequencing and machine learning provide candidate drugs against drug-tolerant persister cells in colorectal cancer

Article

Author: Yao, Ryoji ; Suzuki, Takashi ; Nojima, Yosui

Drug resistance often stems from drug-tolerant persister (DTP) cells in cancer. These cells arise from various lineages and exhibit complex dynamics. However, effectively targeting DTP cells remains challenging. We used single-cell RNA sequencing (scRNA-Seq) data and machine learning (ML) models to identify DTP cells in patient-derived organoids (PDOs) and computationally screened candidate drugs targeting these cells in familial adenomatous polyposis (FAP), associated with a high risk of colorectal cancer. Three PDOs (benign and malignant tumor organoids and a normal organoid) were evaluated using scRNA-Seq. ML models constructed based on public scRNA-Seq data classified DTP versus non-DTP cells. Candidate drugs for DTP cells in a malignant tumor organoid were identified from public drug sensitivity data. From FAP scRNA-Seq data, a specific TC1 cell cluster in tumor organoids was identified. The ML model identified up to 36 % of TC1 cells as DTP cells, a higher proportion than those for other clusters. A viability assay using a malignant tumor organoid demonstrated that YM-155 and THZ2 exert synergistic effects with trametinib. The constructed ML model is effective for DTP cell identification based on scRNA-Seq data for FAP and provides candidate treatments. This approach may improve DTP cell targeting in the treatment of colorectal and other cancers.

01 Mar 2025·British Journal of Pharmacology

Disruption of survivin protein expression by treatment with YM155 accelerates the resolution of neutrophilic inflammation

Article

Author: Felix, Franciel Batista ; Pinho, Vanessa ; Queiroz‐Junior, Celso Martins ; Vago, Juliana Priscila ; Teixeira, Mauro Martins ; Santos, Anna Clara Paiva Menezes Dos ; Amaral, Flávio Almeida ; Beltrami, Vinicius Amorim ; Soriani, Frederico Marianetti ; Fernandes, Débora de Oliveira ; Machado, Jessica Rayssa

Abstract:

Background and Purpose:

Prolonged survival of neutrophils is essential for determining the progression and severity of inflammatory and immune‐mediated disorders, including gouty arthritis. Survivin, an anti‐apoptotic molecule, has been described as a regulator of cell survival. This study aims to examine the effects of YM155 treatment, a survivin selective suppressant, in maintaining neutrophil survival in vitro and in vivo experimental settings of neutrophilic inflammation.

Experimental approach:

BALB/c mice were injected with monosodium urate (MSU) crystals and treated with YM155 (intra‐articularly) at the peak of inflammatory response. Leukocyte recruitment, apoptosis neutrophil and efferocytosis were determined by knee joint wash cell morphology counting and flow cytometry. Resolution interval (Ri) was quantified by neutrophil infiltration, monitoring the amplitude and duration of the inflammation. Cytokine production was measured by ELISA. Mechanical hypernociception was assessed using an electronic von Frey aesthesiometer. Efferocytosis was evaluated in zymosan‐induced neutrophilic peritonitis. Survivin and cleaved caspase‐3 expression was determined in human neutrophils by flow cytometry.

Key Results:

Survivin was expressed in neutrophils during MSU‐induced gout, and the treatment with YM155 reduced survivin expression and shortened Ri from ∼8 h observed in vehicle‐treated mice to ∼5.5 h, effect accompanied by increased neutrophil apoptosis and efferocytosis, both crucial for the inflammation resolution. Reduced IL‐1β and CXCL1 levels were also observed in periarticular tissue. YM155 reduced histopathological score and hypernociceptive response. In human neutrophils, lipopolysaccharide (LPS) increased survivin expression, whereas survivin inhibition with YM155 induced neutrophil apoptosis, with activation of caspase‐3.

Conclusions and Implications:

Survivin may be a promising therapeutic target to control neutrophilic inflammation.

01 Dec 2024·Hematology Transfusion and Cell Therapy

The survivin/XIAP suppressant YM155 impairs clonal growth and induces apoptosis in JAK2V617F cells

Article

Author: Lima, Keli ; Costa-Lotufo, Leticia Veras ; Rego, Eduardo Magalhães ; Machado-Neto, João Agostinho ; Carlos, Jorge Antonio Elias Godoy

The central role of the control of apoptosis in the pathophysiology of Philadelphia chromosome-negative myeloproliferative neoplasms has recently been reinforced in genetic and pharmacological studies. The inhibitor of apoptosis protein family has eight members and plays an important role in apoptosis, with the most studied being survivin (BIRC5) and X-linked inhibitor of apoptosis (XIAP). YM155 is a small molecule with antineoplastic potential that has been described as a suppressant of survivin and XIAP. In the present study, BIRC5 expression was significantly increased in primary myelofibrosis patients compared to healthy donors. On the other hand, XIAP expression was reduced in myeloproliferative neoplasms patients. In JAK2^V617F cells, YM155 reduces cell viability and autonomous clonal growth and induces apoptosis, cell cycle arrest, and autophagy. HEL cells that show greater malignancy are more sensitive to the drug than SET2 cells. In the molecular scenario, YM155 modulates apoptosis-, cell cycle-, DNA damage- and autophagy-related genes. Protein expression analysis corroborates the observed cellular phenotype and exploratory gene expression findings. In summary, our results indicate that survivin/BIRC5 and XIAP are differently expressed in myeloproliferative neoplasms and YM155 has multiple antineoplastic effects on JAK2^V617F cells suggesting that inhibitor of apoptosis proteins may be a target for pharmacological interventions in the treatment of these diseases.

1

News (Medical) associated with Sepantronium Bromide

19 Dec 2022

·www.biospace.com

Cothera Announces Dosing of First Patient in Phase 2 Clinical Trial to Test Its DUB Inhibitor PC-002 for the Treatment of High-Grade B-cell Lymphoma

San Francisco, December 19, 2022--Cothera Bioscience today announced that it has dosed the first patient with PC-002, a first-in-class deubiquitinase (DUB) inhibitor, in a global multi-center phase 2 clinical trial for the treatment of high-grade B-cell lymphoma with Myc rearrangement (NCT05263583). This is a single-arm, single-agent proof-of-concept trial designed to evaluate PC-002 in patients who are either resistant or refractory to prior treatments. The company also announced that a paper1 describing PC-002’s mechanism-of-action was accepted for publication in the European Journal of Pharmaceutical Science. PC-002 (also known as YM155, sepantronium bromide) is a first-in-class small molecule inhibitor of DUB, an enzyme family which removes ubiquitin from cellular proteins otherwise destined for degradation. By inhibiting a key DUB activity that stabilizes the Myc protein in cancer cells, PC-002 selectively induces Myc protein degradation and cell apoptosis in Myc-dependent tumors. As Myc is regarded as one of the most important yet “undruggable” cancer targets with increased expression in more than 50% of human cancers, PC-002 may potentially address multiple cancer indications involving Myc dysregulation. Dr. Alex Wu, Co-founder and CEO of Cothera Bioscience, commented: "We are excited to dose the first patient in this important proof-of-concept trial. DUBs are an emerging target family with broad potential in cancer and inflammation treatment. PC-002 is the most advanced clinical stage DUB inhibitor which works by accelerating the degradation of Myc oncoprotein and has great potential to treat cancers depending on high Myc activity. Myc-driven high-grade lymphoma is a highly malignant, life-threatening disease for which there is currently no good treatment. We look forward to validating the safety and efficacy of PC-002 through this trial, providing a new solution for improving the prognosis of patients with this devastating disease, and delivering a breakthrough in the treatment of Myc-driven tumors.” 1. Li et al. YM155 Inhibits Neuroblastoma Growth through Degradation of MYCN: A New Role as a USP7 Inhibitor, European Journal of Pharmaceutical Sciences (2022) doi: About Cothera Bioscience, Inc. Cothera Bioscience is a clinical stage biotech company developing therapeutics for previously undruggable oncology targets with high unmet medical needs. The company’s strength is in its clinically validated translational platform exploiting synthetic lethality and protein degradation pathways for cancer killing. It was formed by the core founding members of Crown Bioscience, a leading contract research organization specializing in translational oncology, together with veteran serial entrepreneurs from Silicon Valley. Proprietary i-CR® technology platform Cothera Bioscience developed a patented proprietary i-CR® technology platform, a powerful method for individualized drug screening and new drug development. The platform combines a high content screening system with conditional reprogramming of primary cultured tumor cells, which enables efficient and undifferentiated expansion of primary patient-derived tumor cells in vitro while preserving the tumor’s heterogeneity. Through collaboration with leading oncology medical centers, Cothera Bioscience carried out prospective clinical trials and demonstrated that the i-CR® system can effectively predict the actual clinical response of a drug, with potential to significantly improve the clinical efficacy and success rate in anticancer drug development. (Transl Oncol. 2021 Jan;14(1):100935). For more information, please visit or send email to: bd@cotherabio.com

Phase 2

100 Deals associated with Sepantronium Bromide

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External Link

KEGG	Wiki	ATC	Drug Bank
D10164	-	-	-

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
C-Myc Rearrangement B-Cell Lymphoma	Phase 2	CN	Haikou Kerui Hua Biotechnology Corporation Limited	14 Jul 2022
C-Myc Rearrangement B-Cell Lymphoma	Phase 2	CN	Beijing Percans Oncology Co., Ltd.	14 Jul 2022
C-Myc Rearrangement B-Cell Lymphoma	Phase 2	KR	Beijing Percans Oncology Co., Ltd.	14 Jul 2022
C-Myc Rearrangement B-Cell Lymphoma	Phase 2	KR	Haikou Kerui Hua Biotechnology Corporation Limited	14 Jul 2022
Advanced Lung Non-Small Cell Carcinoma	Phase 2	US	National Cancer Institute	01 Feb 2010
HER2-negative breast cancer	Phase 2	US	Astellas Pharma, Inc.	01 Dec 2009
HER2-negative breast cancer	Phase 2	BE	Astellas Pharma, Inc.	01 Dec 2009
HER2-negative breast cancer	Phase 2	CZ	Astellas Pharma, Inc.	01 Dec 2009
HER2-negative breast cancer	Phase 2	DE	Astellas Pharma, Inc.	01 Dec 2009
HER2-negative breast cancer	Phase 2	IE	Astellas Pharma, Inc.	01 Dec 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05263583 (ASH2023)	Phase 2	C-Myc positive High grade B-cell lymphoma	-	PC-002 (Sepantronium Bromide, or SepB)	vkrfzhnnfb(imdtlpfqxv) = edkqpxhmij eyxiyhbrau (adsrbqrcen )	-	09 Dec 2023
NCT01007292 (Pubmed \| Leukemia) Manual	Phase 2	Aggressive B-Cell Non-Hodgkin Lymphoma	41	YM155+Rituximab	dlujgjxhjr(zvejpysfph) = wkxdtmbror pbuksvjynd (enlicppthh ) View more	Negative	01 Aug 2016
ASCO2016	Phase 1	EGFR-mutated non-small Cell Lung Cancer	18	YM155 + Erlotinib	qhxpxmremi(hdheimxbph) = One patient receiving 4.8 mg/ m2/d Y developed a dose-limiting transient reversible grade 2 serum creatinine elevation ncaqrknczo (ykwukvizgy ) View more	Positive	20 May 2016
NCT01009775 (Pubmed \| Cancer Med) Manual	Phase 2	Melanoma	64	docetaxel+YM155	ikpnebvixb(wfadxoryec) = zlcikpdtdo sicbjpejbr (emwvuqgdef, 21.3 - 48.6) View more	Negative	01 May 2015
NCT01038804 (ASCO2013) Manual	Phase 2	HER2-negative breast cancer First line HER2 negative	101	docetaxel+YM155	qobizaipmz(aeiytnunrj) = djskouyols wsmgaxmadn (ggjyflrznp, 176 - 333) View more	Positive	20 May 2013
NCT01038804 (ASCO2013) Manual	Phase 2	HER2-negative breast cancer First line HER2 negative	101	docetaxel	qobizaipmz(aeiytnunrj) = ghvxrtkclw wsmgaxmadn (ggjyflrznp, 202 - 433) View more	Positive	20 May 2013
E1611 (ASCO2012)	Not Applicable	Merkel Cell Carcinoma	-	YM155	skquaqkbjr(kojiduqtxe) = uuqynjhphb iloxerbsvl (fpuvmunlpc )	-	20 May 2012
E1611 (ASCO2012)	Not Applicable	Merkel Cell Carcinoma	-	Bortezomib	skquaqkbjr(kojiduqtxe) = vdryoujmvn iloxerbsvl (fpuvmunlpc )	-	20 May 2012
ASCO2012	Phase 2	Melanoma	64	YM155 plus docetaxel	cheudbssuc(dwwktoueqy) = umkuaczskl rofpgkgcxy (bawkfoywwf ) View more	Negative	20 May 2012
ASCO2009	Not Applicable	Diffuse Large B-Cell Lymphoma	43	YM155	gfmifuczdm(eflvqekkuf) = rqkqtsdcsr netzjiwrmw (kmpacysyvr ) View more	-	20 May 2009
ASCO2007	Phase 1	HR-positive/HER2-low Solid Tumors	34	YM155	uiohplgwll(ureojxookd) = bcmbcnabsf xskfebircs (ugvqbmvuok )	-	20 Jun 2007
ASCO2006	Phase 1	HR-positive/HER2-low Solid Tumors	41	YM155	nsyzaufwug(woufnzrybx) = qzxzmlusyw bnugeqhsup (ygwdtitkhw )	-	20 Jun 2006