Delving into the Latest Updates on Obatoclax mesylate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Obatoclax, Obatoclax mesylate (USAN)

+ [3]

Target

Bcl-2

Action

inhibitors

Mechanism

Bcl-2 inhibitors(Apoptosis regulator Bcl-2 inhibitors)

Therapeutic Areas

NeoplasmsRespiratory DiseasesImmune System Diseases+ [3]

Active Indication-

Inactive Indication

Acute Myeloid LeukemiaAnemiaAnemia, Aplastic+ [12]

Originator Organization

Teva Pharmaceutical Industries Ltd.

Active Organization-

Inactive Organization

Gemin X Pharmaceuticals US, Inc.Gemin X Biotechnologies

Cephalon, Inc.

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationOrphan Drug (United States)

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Structure/Sequence

Molecular FormulaC21H23N3O4S

InChIKeyZFKXDVMHNXPEIY-UHFFFAOYSA-N

CAS Registry803712-79-0

View All Structures (2)

This is a randomized, multi-center, open-label study of approximately 24 months duration (including follow up survival) to evaluate the safety and efficacy of obatoclax mesylate in combination with carboplatin and etoposide versus carboplatin and etoposide alone in chemotherapy-naive patients with extensive-stage small cell lung cancer.

Start Date01 Aug 2012

Sponsor / Collaborator

Cephalon, Inc.

NCT01238146

/ WithdrawnPhase 1/2IIT

A Phase I/II Trial of Rituximab, Bendamustine, and Obatoclax in Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma

This phase I/II trial is studying the side effects and the best dose of obatoclax mesylate when given together with rituximab and bendamustine hydrochloride to see how well it works compared with rituximab and bendamustine hydrochloride alone in treating patients with relapsed or refractory non-Hodgkin lymphoma. Obatoclax mesylate may stop the growth of cancer cells by blocking some of the proteins needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine hydrochloride, also work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving obatoclax mesylate together with rituximab and bendamustine hydrochloride may kill more cancer cells

Start Date01 Oct 2010

Sponsor / Collaborator

National Cancer Institute

EUCTR2008-001679-31-BG

/ Not yet recruitingNot Applicable

A Phase I Followed by a Randomized, Phase II Study of Carboplatin and Etoposide with or without Obatoclax Administered Every 3 Weeks to Patients with Extensive-Stage Small Cell Lung Cancer (ES-SCLC)

Start Date26 Jun 2009

Sponsor / Collaborator

Gemin X Pharmaceuticals US, Inc.

100 Clinical Results associated with Obatoclax mesylate

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100 Translational Medicine associated with Obatoclax mesylate

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100 Patents (Medical) associated with Obatoclax mesylate

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442

Literatures (Medical) associated with Obatoclax mesylate

07 Apr 2025·Oncogene

Frequent copy number gain of MCL1 is a therapeutic target for osteosarcoma

Article

Author: Katayama, Ryohei ; Nakajima, Mikako ; Takemoto, Ai ; Takami, Miho ; Huang, Tianyi ; Baba, Satoko ; Koike, Sumie ; Sugiura, Yoshiya ; Saito, Masanori ; Takeuchi, Kengo ; Ae, Keisuke ; Fujita, Naoya ; Takagi, Satoshi ; Funauchi, Yuki ; Sakata, Seiji ; Seto, Yosuke

Osteosarcoma (OS) is a primary malignant bone tumor primarily affecting children and adolescents. The lack of progress in drug development for OS is partly due to unidentified actionable oncogenic drivers common to OS. In this study, we demonstrate that copy number gains of MCL1 frequently occur in OS, leading to vulnerability to therapies based on Mcl-1 inhibitors. Fluorescence in situ hybridization analysis of 41 specimens revealed MCL1 amplification in 46.3% of patients with OS. Genetic inhibition of MCL1 induced significant apoptosis in MCL1-amplified OS cells, and the pharmacological efficacy of Mcl-1 inhibitors was correlated with MCL1 copy numbers. Chromosome 1q21.2-3 region, where MCL1 is located, contains multiple genes related to the IGF-1R/PI3K pathway, including PIP5K1A, TARS2, OUTD7B, and ENSA, which also showed increased copy numbers in MCL1-amplified OS cells. Furthermore, combining Mcl-1 inhibitors with IGF-1R inhibitors resulted in synergistic cell death by overcoming drug tolerance conferred by the activation of IGF signaling and suppressed tumor growth in MCL1-amplified OS xenograft models. These results suggest that genomic amplification of MCL1 in the 1q21.2-3 region, which occurred in approximately half of OS patients, may serve as a predictive biomarker for the combination therapy with an Mcl-1 inhibitor and an IGF1R inhibitor.

01 Mar 2025·Molecular Oncology

Inhibition of autophagy as a novel treatment for neurofibromatosis type 1 tumors

Article

Author: Bouley, Stephanie J. ; Stevens, Megan ; Wang, Yuanli ; Housden, Benjamin E. ; Sharma, Aditi ; Perrimon, Norbert ; Sengupta, Sonali ; Mandigo, Torrey R. ; Walker, James A. ; Housden, Amy

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutation of the NF1 gene that is associated with various symptoms, including the formation of benign tumors, called neurofibromas, within nerves. Drug treatments are currently limited. The mitogen‐activated protein kinase kinase (MEK) inhibitor selumetinib is used for a subset of plexiform neurofibromas (PNs) but is not always effective and can cause side effects. Therefore, there is a clear need to discover new drugs to target NF1‐deficient tumor cells. Using a Drosophila cell model of NF1, we performed synthetic lethal screens to identify novel drug targets. We identified 54 gene candidates, which were validated with variable dose analysis as a secondary screen. Pathways associated with five candidates could be targeted using existing drugs. Among these, chloroquine (CQ) and bafilomycin A1, known to target the autophagy pathway, showed the greatest potential for selectively killing NF1‐deficient Drosophila cells. When further investigating autophagy‐related genes, we found that 14 out of 30 genes tested had a synthetic lethal interaction with NF1. These 14 genes are involved in multiple aspects of the autophagy pathway and can be targeted with additional drugs that mediate the autophagy pathway, although CQ was the most effective. The lethal effect of autophagy inhibitors was conserved in a panel of human NF1‐deficient Schwann cell lines, highlighting their translational potential. The effect of CQ was also conserved in a Drosophila NF1 in vivo model and in a xenografted NF1‐deficient tumor cell line grown in mice, with CQ treatment resulting in a more significant reduction in tumor growth than selumetinib treatment. Furthermore, combined treatment with CQ and selumetinib resulted in a further reduction in NF1‐deficient cell viability. In conclusion, NF1‐deficient cells are vulnerable to disruption of the autophagy pathway. This pathway represents a promising target for the treatment of NF1‐associated tumors, and we identified CQ as a candidate drug for the treatment of NF1 tumors.

01 Mar 2025·Biochemical and Biophysical Research Communications

Withania somnifera-derived phytochemicals as Bcl-B inhibitors in cancer therapy: A computational approach from byte to bench to bedside

Article

Author: Muthukumaran, Jayaraman ; Dhillon, Deepika ; Jain, Monika ; Singh, Amit Kumar

Cancer is the second foremost cause of fatalities associated with non-communicable diseases across the globe, affecting multiple organs and often necessitating costly treatments with adverse side effects. Apoptosis, the body's natural cell death process, plays a crucial role in the prevention of cancer, but it's often disrupted in cancer cells, allowing uncontrolled proliferation. Restoring apoptosis in cancer cells is one of the promising therapeutic strategies to curb tumor growth and enhance clinical outcomes. Bcl-B, an anti-apoptotic protein within the Bcl-2 family, interacts with Bax to mitigate apoptosis, indicating it as a druggable target for cancer therapy. There's a critical need for natural, cost-effective alternatives with minimal adverse effects to reduce morbidity rates of cancer patients. Plant-based immunoprotective medications, particularly from sustainable sources like known medicinal plants, offer substantial potential for cancer treatment. This study involves comprehensive in silico approaches (byte) to evaluate the inhibition potential of the phytochemicals derived from Withania somnifera against the anti-apoptotic Bcl-B protein. Research into Bcl-B's binding affinity with 80 phytochemicals from this plant aims to identify interaction sites for promising anticancer agents. This study's focus on Bcl-B protein highlights its potential in modulating apoptotic pathways and exploring novel anti-cancer therapeutics. Through comprehensive screening based on drug-likeness and pharmacokinetic properties, combined with in-house virtual screening, molecular docking, molecular dynamics simulations, and MM/PBSA-based binding free energy analysis, three promising candidate inhibitors-Withanolide L (IMPHY009438), Withanolide M (IMPHY003143), and Withanolide A (IMPHY000090)-were identified and prioritized. These candidates showed favorable estimated binding free energy values, along with desirable drug-likeness and pharmacokinetic profiles. The results demonstrated that the selected and prioritized phytochemicals, Withanolide L, Withanolide M, and Withanolide A display comparable efficacy to Obatoclax (CID: 11404337) and other known synthetic, semi-synthetic, and natural inhibitors of Bcl-2 family proteins. These findings establish a strong bench foundation for further experimental validation and bedside application, potentially offering an alternative natural approach to cancer therapy.

100 Deals associated with Obatoclax mesylate

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External Link

KEGG	Wiki	ATC	Drug Bank
D08954	Obatoclax mesylate	-	DB12191

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Extensive stage Small Cell Lung Cancer	Phase 3	-	Cephalon, Inc.	01 Aug 2012
Extensive stage Small Cell Lung Cancer	Phase 3	-	Cephalon, Inc.	01 Aug 2012
Primary Myelofibrosis	Phase 3	Canada	Gemin X Biotechnologies	-
Primary Myelofibrosis	Phase 3	United States	Gemin X Biotechnologies	-
Primary Myelofibrosis	Phase 3	United States	Gemin X Biotechnologies	-
Primary Myelofibrosis	Phase 3	Canada	Gemin X Biotechnologies	-
Small Cell Lung Cancer	Phase 3	Hungary	Gemin X Biotechnologies	-
Small Cell Lung Cancer	Phase 3	Poland	Gemin X Biotechnologies	-
Small Cell Lung Cancer	Phase 3	India	Gemin X Biotechnologies	-
Systemic Mastocytosis	Phase 3	United States	Gemin X Biotechnologies	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00719901 (CTgov)	Phase 1/2	Relapse multiple myeloma \| Refractory Multiple Myeloma	11	laboratory biomarker analysis+obatoclax mesylate+bortezomib	gzelbnlzps(sxosqntwgw) = acuvuoelmc eztkzwumtp (ojyiimakmj, byuwlkyuab - wtychhwhsu) View more	-	09 Dec 2013
ASCO2012	Phase 1	Relapse multiple myeloma	11	Obatoclax mesylate	(delnbfjrqn) = 4 DLTs were seen: at original dose level 1 grade 4 thrombocytopenia and delay of therapy > 15 days. At dose level 2, 1 patient had grade 3 somnolence, a 2nd patient grade 3 euphoria and grade 4 thrombocytopenia. No DLTs were seen at amended dose level 1 kxyucptxfy (buqlzngaox ) View more	-	20 May 2012
NCT00521144 (Pubmed \| Lung Cancer)	Phase 2	Small Cell Lung Cancer	22	Obatoclax mesylate plus topotecan	cjhwnwmvdg(brynapsxui) = 11% jlmftthtsf (vlunnfbrgt ) View more	Negative	01 Dec 2011
NCT00918931 (CTgov)	Phase 2	Systemic Mastocytosis \| Leukemia	3	Obatoclax Mesylate	(znghawjoip) = tlobewtfkp rjbpeqglwq (boeklazcxp, xarorkpwvo - owxatiukmq) View more	-	25 Apr 2011