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+ [4]

Active Indication-

Inactive Indication

Acute Lymphoblastic LeukemiaAcute Myeloid LeukemiaAdvanced Malignant Solid Neoplasm+ [29]

Originator Organization

Teva Pharmaceutical Industries Ltd.

Active Organization-

Inactive Organization

Gemin X BiotechnologiesGemin X Pharmaceuticals US, Inc.

National Cancer Institute

+ [1]

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationOrphan Drug (US)

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

NCT00918931 / TerminatedPhase 2IIT

Evaluation of Obatoclax Mesylate as Therapy for Patients With Systemic Mastocytosis

The goal of this clinical research study is to learn if obatoclax mesylate can help to control systemic mastocytosis. The safety of this drug will also be tested.

Start Date01 Jun 2009

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+1]

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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238

Literatures (Medical) associated with Obatoclax mesylate

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: Wu, Ziyao ; Ma, Chengnuo ; Li, Axing ; Zhou, Chenliang ; Zhou, Ruijing ; Duan, Heng ; Li, Ting ; Peng, Jie ; Zhong, Xuelin ; 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.

01 Oct 2023·iScience

Development of novel cytoprotective small compounds inhibiting mitochondria-dependent cell death

Article

Author: Matsuyama, Shigemi ; Scott-McKean, Jonah ; Matsuyama, Mieko ; Adams, Drew ; Ortega, Joseph T ; Greenlee, William ; Buck, Matthias ; Muller-Greven, Jeannie ; Jastrzebska, Beata ; Fedorov, Yuri

We identified cytoprotective small molecules (CSMs) by a cell-based high-throughput screening of Bax inhibitors. Through a medicinal chemistry program, M109S was developed, which is orally bioactive and penetrates the blood-brain/retina barriers. M109S protected retinal cells in ocular disease mouse models. M109S directly interacted with Bax and inhibited the conformational change and mitochondrial translocation of Bax. M109S inhibited ABT-737-induced apoptosis both in Bax-only and Bak-only mouse embryonic fibroblasts. M109S also inhibited apoptosis induced by staurosporine, etoposide, and obatoclax. M109S decreased maximal mitochondrial oxygen consumption rate and reactive oxygen species production, whereas it increased glycolysis. These effects on cellular metabolism may contribute to the cytoprotective activity of M109S. M109S is a novel small molecule protecting cells from mitochondria-dependent apoptosis both in vitro and in vivo. M109S has the potential to become a research tool for studying cell death mechanisms and to develop therapeutics targeting mitochondria-dependent cell death pathway.

01 Oct 2023·Toxicological research

Atg5 knockout induces alternative autophagy via the downregulation of Akt expression.

Article

Author: Ro, Myeong-Han ; Lee, Michael ; Kim, Hye-Gyo

Autophagy play contradictory roles in cellular transformation. We previously found that the knockout (KO) of autophagy-related 5 (Atg5), which is essential for autophagy, leads to the malignant transformation of NIH 3T3 cells. In this study, we explored the mechanism by which autophagy contributes to this malignant transformation using two transformed cell lines, Atg5 KO and Ras-NIH 3T3. Monomeric red fluorescent protein-green fluorescent protein-light chain 3 reporter and Cyto-ID staining revealed that Ras-NIH 3T3 cells exhibited higher basal autophagy activity than NIH 3T3 cells. Additionally, transformed cells, regardless of their Atg5 KO status, were more sensitive to autophagy inhibitors (SBI-0206965, chloroquine, and obatoclax) than the untransformed NIH 3T3 cells, suggesting that the transformed cells are more autophagy-dependent than the normal cells. Loss of Atg5 improved the cell viability and mobility, especially in Ras-NIH 3T3 cells. Furthermore, we discovered that autophagy was alternatively induced in a Rab9-dependent manner in Ras-NIH 3T3 and NIH 3T3/Atg5 KO cells. In particular, Atg5 KO cells showed reduced mTOR-mediated phosphorylation of Akt (pAkt S473), indicating the mTOR-independent occurrence of alternative autophagy in Atg5 KO cells. Therefore, our study provides evidence that alternative autophagy may contribute to tumorigenesis in cells with an impaired Atg5-dependent autophagy pathway.Supplementary InformationThe online version contains supplementary material available at 10.1007/s43188-023-00191-3.

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
Chronic Lymphocytic Leukemia	Phase 3	CA	Gemin X Biotechnologies	-
Chronic Lymphocytic Leukemia	Phase 3	US	Gemin X Biotechnologies	-
Primary Myelofibrosis	Phase 3	CA	Gemin X Biotechnologies	-
Chronic Lymphocytic Leukemia	Phase 2	CA	Gemin X Biotechnologies	-
Primary Myelofibrosis	Phase 2	US	Gemin X Biotechnologies	-
Primary Myelofibrosis	Phase 2	CA	Gemin X Biotechnologies	-
Primary Myelofibrosis	Phase 2	US	Gemin X Biotechnologies	-
Chronic Lymphocytic Leukemia	Phase 1	US	Gemin X Biotechnologies	-
Extensive stage Small Cell Lung Cancer	Preclinical	-	Cephalon, Inc.	01 Aug 2012
Extensive stage Small Cell Lung Cancer	Discovery	-	Cephalon, Inc.	01 Aug 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2009	Phase 1	Small cell lung cancer recurrent \| Solid tumor	14	Obatoclax mesylate	(mjgqizlpwy) = sxadzakcfw upvvaxdjih (vjzltihqkg )	-	20 May 2009
NCT00521144 (Pubmed \| Lung Cancer)	Phase 2	Small Cell Lung Cancer	22	Obatoclax mesylate plus topotecan	(zjuthvybpr) = 11% nbvmfkqirk (wwqjbnrksw ) View more	Negative	01 Dec 2011
ASCO2006	Phase 1	Solid tumor \| Lymphoma	15	GX15-070	(oezegquznd) = dbrinqlvzs fwdkrtroee (liszssxatb ) View more	-	20 Jun 2006
NCT00413114 (Pubmed \| Clin Lymphoma Myeloma Leuk)	Phase 2	Anemia \| Thrombocytopenia \| Myelodysplastic Syndromes First line	24	Obatoclax mesylate 60 mg	(bgfsrxtmcd) = 21% (5 patients) akiuftebgs (efhofmujch ) View more	Negative	01 Dec 2014
AACR2011	Not Applicable	Thymic Epithelial Tumor CDKN2A-negative	-	Gx15-070	fqabdonhjy(epcdrxrheq) = srahofmjai xvcxtvjcoj (lxowikhvhh )	-	15 Apr 2011
NCT00682981 (Pubmed \| Lung Cancer)	Phase 2	Extensive stage Small Cell Lung Cancer	155	Carboplatin/etoposide with obatoclax mesylate	(gwnjyshzxj) = vtzpufmzfn rlirgbamnm (invhlqipcx ) View more	Negative	01 Sep 2014
NCT00682981 (Pubmed \| Lung Cancer)	Phase 2	Extensive stage Small Cell Lung Cancer	155	Carboplatin/etoposideCarboplatin/etoposide	(gwnjyshzxj) = djmbbdghdp rlirgbamnm (invhlqipcx ) 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)	aqrtudxbuc(hvvgitrhzg) = two of three patients receiving obatoclax 30 mg/day (3 h × 3 d) experienced grade 3 neurologic DLTs (confusion, ataxia, and somnolence) ywvcbfssoj (fzzxdjvkib ) 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
NCT00521144 (CTgov)	Phase 1/2	Advanced Malignant Solid Neoplasm \| Small cell lung cancer recurrent	22	Obatoclax Mesylate+Topetecan (Phase I; Level 1: Obatoclax Mesylate + Topetecan)	(jcerdsspaj) = vhsuvpsuyc kyfdwnabll (bzxgipgkio, ljftfspcsc - ehciodfwve)	-	22 Jul 2014
NCT00521144 (CTgov)	Phase 1/2		22	Obatoclax Mesylate+Topetecan (Phase I; Level 2: Obatoclax Mesylate + Topetecan)	(jcerdsspaj) = wvyeqillqr kyfdwnabll (bzxgipgkio, trtcbffwdh - lhctoecbtu)	-	22 Jul 2014
NCT00719901 (CTgov)	Phase 1/2	Plasma cell myeloma refractory \| Relapse multiple myeloma	11	laboratory biomarker analysis+obatoclax mesylate+Bortezomib	ndbngwdojd(jbhnuxhtmd) = beqjxyvxcg gzmmwnhfbd (ybnwqkmsxo, kzekscaodd - obetzdqfor) View more	-	09 Dec 2013
ASCO2012	Phase 1	Relapse multiple myeloma	11	Obatoclax mesylate	(yjvmtelchy) = 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 elnnewabid (hstdljyudh ) View more	-	20 May 2012