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

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 (US)

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Structure

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

NCT00933985 / TerminatedPhase 1IIT

A Phase I Study of Obatoclax (Pan Anti-Apoptotic BCL-2 Family Small Molecule Inhibitor), in Combination With Vincristine/Doxorubicin/Dexrazoxane, in Children With Relapsed/Refractory Solid Tumors or Leukemia

This phase I trial is studying the side effects and best dose of obatoclax mesylate when given together with vincristine sulfate, doxorubicin hydrochloride, and dexrazoxane hydrochloride in treating young patients with relapsed or refractory solid tumors, lymphoma, or leukemia. Obatoclax mesylate may stop the growth of cancer cells by blocking some of the proteins needed for cell growth and causing the cells to self-destruct. Drugs used in chemotherapy, such as vincristine sulfate, doxorubicin hydrochloride, and dexrazoxane hydrochloride, 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 combination chemotherapy may kill more cancer cells.

Start Date01 Jun 2009

Sponsor / Collaborator

National Cancer Institute

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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239

Literatures (Medical) associated with Obatoclax mesylate

15 Jul 2024·AIDS

Differential susceptibility of cells infected with defective and intact HIV proviruses to killing by obatoclax and other small molecules

Article

Author: Janssens, Julie ; Telwatte, Sushama ; Wedrychowski, Adam ; Kadiyala, Gayatri Nikhila ; Kim, Sun Jin ; Yukl, Steven A. ; Kim, Peggy ; Wong, Joseph K. ; Deeks, Steven

Objectives:Some drugs that augment cell-intrinsic defenses or modulate cell death/survival pathways have been reported to selectively kill cells infected with HIV or Simian Immunodeficiency Virus (SIV), but comparative studies are lacking. We hypothesized that these drugs may differ in their ability to kill cells infected with intact and defective proviruses.Design:To investigate this hypothesis, drugs were tested ex vivo on peripheral blood mononuclear cells (PBMC) from nine antiretroviral therapy (ART)-suppressed individuals.Methods:We tested drugs currently in clinical use or human trials, including auranofin (p53 modulator), interferon alpha2A, interferon gamma, acitretin (RIG-I inducer), GS-9620/vesatolimod (TLR7 agonist), nivolumab (PD-1 blocker), obatoclax (Bcl-2 inhibitor), birinapant [inhibitor of apoptosis proteins (IAP) inhibitor], bortezomib (proteasome inhibitor), and INK128/sapanisertib [mammalian target of rapamycin mTOR] [c]1/2 inhibitor). After 6 days of treatment, we measured cell counts/viabilities and quantified levels of total, intact, and defective HIV DNA by droplet digital PCR (Intact Proviral DNA Assay).Results:Obatoclax reduced intact HIV DNA [median = 27–30% of dimethyl sulfoxide control (DMSO)] but not defective or total HIV DNA. Other drugs showed no statistically significant effects.Conclusion:Obatoclax and other Bcl-2 inhibitors deserve further study in combination therapies aimed at reducing the intact HIV reservoir in order to achieve a functional cure and/or reduce HIV-associated immune activation.

01 Jul 2024·iScience

Identification of mitochondria-related gene biomarkers associated with immune infiltration in acute myocardial infarction

Article

Author: Xie, Jian ; Wang, Min ; Lv, Xiangwen ; Guan, Yuting ; Liu, Guoqing ; Li, Jingqi

Mitochondrial dysfunction has been known to contribute to the worsening of acute myocardial infarction (AMI). We screened differentially expressed genes (DEGs) between AMI and healthy individuals based on the GSE66360 dataset. We took the intersection of the obtained DEGs with 1,136 mitochondria-related genes. Finally, we screened out mitochondria-related DEGs (MitoDEGs). Eight MitoDEGs were identified as hub genes based on the random forest algorithm. Two mitochondria-related robust molecular clusters were identified by consensus clustering. Immune infiltration analysis showed that immune cell infiltration was significantly increased in the high-expression group of MitoDEGs. We obtained the potential drugs targeted at ALDH2, PMAIP1, and BCL2A1, such as disulfiram, obatoclax mesylate, and bortezomib. Quantitative reverse-transcription polymerase chain reaction further validated the expression of the MitoDEGs in the cell model of AMI. These findings reveal the potential role of MitoDEGs in AMI and provide new insights into risk stratification and individualized treatment of AMI patients.

10 Nov 2023·ACS Infectious Diseases

Bcl-2 Antagonist Obatoclax Reactivates Latent HIV-1 via the NF-κB Pathway and Induces Latent Reservoir Cell Apoptosis in Latently Infected Cells

Article

Author: Ma, Chengnuo ; Wu, Ziyao ; Li, Axing ; Zhou, Chenliang ; Zhou, Ruijing ; Duan, Heng ; Li, Ting ; Zhong, Xuelin ; Peng, Jie ; Rashid, Huba Khamis ; Xia, Muye ; Zhang, Xuanxuan ; Li, Lin

The implementation of combined antiretroviral therapy (cART) has rendered HIV-1 infection clinically manageable and efficiently improves the quality of life for patients with AIDS. However, the persistence of a latent HIV-1 reservoir is a major obstacle to achieving a cure for AIDS. A "shock and kill" strategy aims to reactivate latent HIV and then kill it by the immune system or cART drugs. To date, none of the LRA candidates has yet demonstrated effectiveness in achieving a promising functional cure. Interestingly, the phosphorylation and activation of antiapoptotic Bcl-2 protein induce resistance to apoptosis during HIV-1 infection and the reactivation of HIV-1 latency in central memory CD4⁺ T cells from HIV-1-positive patients. Therefore, a Bcl-2 antagonist might be an effective LRA candidate for HIV-1 cure. In this study, we reported that a pan-Bcl-2 antagonist obatoclax induces HIV-1 reactivation in latently infected cell lines in vitro and in PBMCs/CD4⁺ T cells of HIV-infected individuals ex vivo. Obatoclax promotes HIV-1 transcriptional initiation and elongation by regulating the NF-κB pathway. Obatoclax activates caspase 8 and does not induce the phosphorylation of the antiapoptotic protein Bcl-2 in latent HIV-1 infected cell lines. More importantly, it preferentially induces apoptosis in latently infected cells. In addition, obatoclax exhibited potent anti-HIV-1 activity on target cells. The abilities to reactivate latent HIV-1 reservoirs, inhibit HIV-1 infection, and induce HIV-1 latent cell apoptosis make obatoclax worth investigating for development as an ideal LRA for use in the "shock and kill" approach.

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
Follicular Lymphoma	Phase 3	US	Gemin X Biotechnologies	-
Small Cell Lung Cancer	Phase 3	HU	Gemin X Biotechnologies	-
Small Cell Lung Cancer	Phase 3	CA	Gemin X Biotechnologies	-
Small Cell Lung Cancer	Phase 3	US	Gemin X Biotechnologies	-
Small Cell Lung Cancer	Phase 3	BG	Gemin X Biotechnologies	-
Systemic Mastocytosis	Phase 3	US	Gemin X Biotechnologies	-
Extensive stage Small Cell Lung Cancer	Phase 2	-	Cephalon, Inc.	01 Aug 2012
Small Cell Lung Cancer	Preclinical	GB	Gemin X Biotechnologies	-
Follicular Lymphoma	Discovery	US	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


NCT00413114 (Pubmed \| Clin Lymphoma Myeloma Leuk)	Phase 2	Anemia \| Thrombocytopenia \| Myelodysplastic Syndromes First line	24	Obatoclax mesylate 60 mg	(hfrrxmdfpb) = 21% (5 patients) uvlzdnatsz (svjitidwap ) View more	Negative	01 Dec 2014
NCT00682981 (Pubmed \| Lung Cancer)	Phase 2	Extensive stage Small Cell Lung Cancer	155	Carboplatin/etoposide with obatoclax mesylate	(phphhxukza) = jdwswjnwce avwetbbdnv (ihrunxbvar ) View more	Negative	01 Sep 2014
NCT00682981 (Pubmed \| Lung Cancer)	Phase 2	Extensive stage Small Cell Lung Cancer	155	Carboplatin/etoposideCarboplatin/etoposide	(phphhxukza) = dkjytnmyad avwetbbdnv (ihrunxbvar ) View more	Negative	01 Sep 2014
NCT00684918 (Pubmed \| J Biol Chem)	Phase 1/2	Acute Myeloid Leukemia	18	Obatoclax 30 mg/day (3 h × 3 d)	vqpwnnvwvm(hmbundvoxq) = two of three patients receiving obatoclax 30 mg/day (3 h × 3 d) experienced grade 3 neurologic DLTs (confusion, ataxia, and somnolence) ghoozbmbbs (zghyqtxdjt ) View more	-	01 Jan 2014
NCT00684918 (Pubmed \| J Biol Chem)	Phase 1/2	Acute Myeloid Leukemia	18	Obatoclax 20 mg/day (3 h × 3 d)		-	01 Jan 2014
NCT00719901 (CTgov)	Phase 1/2	Relapse multiple myeloma \| Plasma cell myeloma refractory	11	laboratory biomarker analysis+obatoclax mesylate+bortezomib	vfrjoaratc(llcopmaxzk) = hcuhqmivps oyyumrcquf (iqmatkpjhn, mubjvgmwel - fwjsudyvil) View more	-	09 Dec 2013
ASCO2012	Phase 1	Relapse multiple myeloma	11	Obatoclax mesylate	(jpduntwdkt) = 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 gxemplmlxz (toqipnknyy ) View more	-	20 May 2012
NCT00521144 (Pubmed \| Lung Cancer)	Phase 2	Small Cell Lung Cancer	22	Obatoclax mesylate plus topotecan	(svppuyjdvd) = 11% dxissiroyf (cfeuixngjs ) View more	Negative	01 Dec 2011
NCT00918931 (CTgov)	Phase 2	Systemic Mastocytosis \| Leukemia	3	Obatoclax Mesylate	ebocabkcsf(auvuwierle) = edrzasnvfq lzjqxetdqj (tvcejpvjdn, ddeqasokhk - nskskrlunw) View more	-	25 Apr 2011