Delving into the Latest Updates on R-(-)-Gossypol Acetic Acid with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

AT-101 (Ascenta Therapeutics), AT101, AT101(Ascenta Therapeutics)

Target

Bcl-2

Action

inhibitors, stimulants

Mechanism

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

Therapeutic Areas

Urogenital DiseasesNeoplasmsHemic and Lymphatic Diseases

Active Indication

EndometriosisAcute Myeloid Leukemia

Inactive Indication

Advanced Lung Non-Small Cell CarcinomaCastration-Resistant Prostatic CancerChronic Lymphocytic Leukemia+ [15]

Originator Organization

University of Michigan College of Engineering

Active Organization

Xian Epang Place Pharmaceutical Co. Ltd.The First Affiliated Hospital of Xiamen University

Inactive Organization

Ascenta Therapeutics, Inc.

Jiangsu Yasheng Pharmaceutical Development Co. Ltd.

3SBio, Inc.

+ [2]

License Organization

Ascentage Pharma Group International Co., Ltd.

Ascenta Therapeutics, Inc.

Drug Highest PhaseApproved

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC32H34O10

InChIKeyNIOHNDKHQHVLKA-UHFFFAOYSA-N

CAS Registry866541-93-7

主要目的：评估AT-101治疗复发GBM患者的安全性。次要目的：评估AT-101治疗复发性GBM患者的总生存期（OS）；评估AT-101治疗复发性GBM患者的无进展生存期（PFS）；评估AT-101治疗复发性GBM患者的总体客观缓解率（ORR）（完全缓解（CR）+部分缓解（PR））、疾病控制率（DCR）（CR+PR+SD ≥ 6周)、疗效持续时间（DOR）。探索性目的：探索Bcl-2家族蛋白表达状态、MGMT基因甲基化状态与临床疗效的相关性。

[Translation]

Primary objective: To evaluate the safety of AT-101 in the treatment of patients with recurrent GBM. Secondary objectives: To evaluate the overall survival (OS) of patients with recurrent GBM treated with AT-101; To evaluate the progression-free survival (PFS) of patients with recurrent GBM treated with AT-101; To evaluate the overall objective response rate (ORR) (complete response (CR) + partial response (PR)), disease control rate (DCR) (CR+PR+SD ≥ 6 weeks), and duration of efficacy (DOR) of patients with recurrent GBM treated with AT-101. Exploratory objective: To explore the correlation between the expression status of Bcl-2 family proteins and the methylation status of the MGMT gene and clinical efficacy.

Start Date20 Oct 2017

Sponsor / Collaborator

Jiangsu Yasheng Pharmaceutical Development Co. Ltd.

CTR20150541

/ TerminatedPhase 2

AT-101联合利妥昔单抗治疗复发或难治性慢性淋巴细胞白血病（CLL）患者的一项开放性、多中心II期临床研究

[Translation] An open-label, multicenter phase II clinical study of AT-101 combined with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia (CLL)

主要目的：评估AT-101联合利妥昔单抗治疗复发或难治性CLL患者的客观缓解率。次要目的：评估AT-101联合利妥昔单抗治疗复发或难治性CLL患者的安全性。评估AT-101联合利妥昔单抗治疗复发或难治性CLL患者的无进展生存期（PFS）和缓解持续时间（DOR）。评估AT-101联合利妥昔单抗治疗复发或难治性CLL患者的生活质量（QoL，FACT-BRM问卷）（部分入组受试者）。

[Translation]

Primary objective: To evaluate the objective response rate of AT-101 combined with rituximab in patients with relapsed or refractory CLL. Secondary objectives: To evaluate the safety of AT-101 combined with rituximab in patients with relapsed or refractory CLL. To evaluate the progression-free survival (PFS) and duration of response (DOR) of AT-101 combined with rituximab in patients with relapsed or refractory CLL. To evaluate the quality of life (QoL, FACT-BRM questionnaire) of AT-101 combined with rituximab in patients with relapsed or refractory CLL (part of the enrolled subjects).

Start Date03 Aug 2017

Sponsor / Collaborator

Jiangsu Yasheng Pharmaceutical Development Co. Ltd.

NCT02697344

/ CompletedPhase 1IIT

Phase I/II Trial of AT-101 in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed Symptomatic Multiple Myeloma

This phase I trial studies the side effects and best dose of R-(-)-gossypol acetic acid when given together with lenalidomide and dexamethasone and to see how well it works in treating patients with multiple myeloma, also known as plasma cell myeloma, that has come back after a period of improvement or has gotten worse after treatment. R-(-)-gossypol acetic acid may stop the growth of cancer cells by recognizing certain proteins and stimulating programmed cell death. Lenalidomide may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving R-(-)-gossypol acetic acid with lenalidomide and dexamethasone may work better in treating patients with multiple myeloma.

Start Date14 Apr 2016

Sponsor / Collaborator

Mayo Clinic

100 Clinical Results associated with R-(-)-Gossypol Acetic Acid

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100 Translational Medicine associated with R-(-)-Gossypol Acetic Acid

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100 Patents (Medical) associated with R-(-)-Gossypol Acetic Acid

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123

Literatures (Medical) associated with R-(-)-Gossypol Acetic Acid

01 Aug 2025·ANNALS OF SURGICAL ONCOLOGY

AT101 Suppresses Gastrointestinal Stromal Tumor Growth and Promotes Apoptosis via YAP/TAZ–CCND1 and FBXW7–MCL1 Axes

Article

Author: Wu, Xiyu ; Zhang, Weiliyun ; Yamashita, Kohei ; Baba, Hideo ; Iwatsuki, Masaaki ; Matsumoto, Chihiro ; Lou, Meiyue

BACKGROUND:

Imatinib (IM), a tyrosine kinase inhibitor (TKI), is the first-line treatment for patients with gastrointestinal stromal tumors (GISTs). However, its efficacy is limited due to acquired resistance induced by secondary KIT mutations in most patients with GIST. Furthermore, new challenges have emerged following the clarification that KIT-independent GISTs exhibit strong resistance to small molecule inhibitors targeting KIT/ platelet-derived growth factor receptor alpha (PDGFRA). Therefore, investigating the underlying therapeutic targets for imatinib-resistant GISTs is urgently necessitated.

PATIENTS AND METHODS:

Through both in vitro and in vivo experiments, along with the analysis of alterations in the FBXW7-MCL1 axis and the YAP/TAZ-CCND1 pathway in patients with GISTs, before and after IM treatment.

RESULTS:

MCL1 overexpression and activation of the YAP/TAZ-CCND1 pathway are induced in IM-resistant GIST cells and post-IM GIST samples. AT101, a BCL-2 inhibitor, exerts a pro-apoptotic effect on GIST cells by suppressing MCL1 overexpression, and the combination therapy of AT101 and IM exerts a stronger pro-apoptotic effect through modulation of IM activity regulated by the FBXW7-MCL1 axis. Furthermore, the suppression of AT101 on GIST growth and metastasis, by targeting the YAP/TAZ-CCND1 pathway, was confirmed through xenograft and metastasis mouse models. Notably, the antitumor activity of AT101 is maintained regardless of the IM sensitivity of GIST cells, whereas AT101 enhances and restores IM activities in both GIST-T1 and IM-resistant GIST cells.

CONCLUSIONS:

AT101 exerts a strong antitumor activity by targeting both the FBXW7-MCL1 axis and the YAP/TAZ-CCND1 pathway, suggesting that AT101 monotherapy, and its combination with IM, are worth further investigating in clinical trials.

02 Jan 2025·Nanomedicine

The anti-glypican 1 AT101 antibody as targeting agent to effectively deliver chitosan nanobubbles to glioblastoma cells

Article

Author: Di Cintio, Federica ; Scomparin, Anna ; Toffoli, Giuseppe ; Mangogna, Alessandro ; Capolla, Sara ; Cavalli, Roberta ; Macor, Paolo ; Dal Bo, Michele ; Sblattero, Daniele ; Argenziano, Monica ; Steffè, Aharon ; Busato, Davide

BACKGROUND:

Recently, we developed AT101, an IgM-class mouse monoclonal antibody directed against glypican-1 (GPC1), a proteoglycan that can be considered as useful target for glioblastoma multiforme (GBM) treatment being specifically and highly expressed on GBM cell surface. Here, we proposed the use of AT101 as targeting agent in a drug delivery nanoplatfom to effectively deliver chitosan nanobubbles (NBs) for GBM treatment.

METHODS:

Chitosan NBs were prepared and conjugated with AT101 or left unconjugated as control.

RESULTS:

The ability of AT101 to bind the GPC1 protein was demonstrated by flow cytometry and immunofluorescence analysis in the "GBM-like" GPC1-expressing cell lines U-87 MG and T98G. AT101 was shown to bind GPC1-expressing GBM tumor samples by immunofluorescence. In-vivo experiments in the U-87 MG xenograft model showed that AT101 was able to bind GPC1 on cell surface and accumulate in U-87 MG tumor masses (p = 0.0002 respect to control). Moreover, in-vivo experiments showed that AT101 is able to target GPC1 when conjugated to chitosan NBs, thus increasing their specific deliver to GPC1-expressing cells of U-87 MG tumor, as compared to chitosan NBs not conjugated to AT101 (p = 0.02).

CONCLUSIONS:

AT101 is an useful targeting agent for the development of drug delivery nanoplatforms for GBM treatment.

01 Oct 2024·BIOORGANIC CHEMISTRY

Discovery and development of thiazolidine-2,4-dione derivatives as Bcl-2/Mcl-1 dual inhibitors

Article

Author: Chen, Hongjuan ; Long, Jiabing ; Deng, Ritian ; Wan, Yichao ; Wang, Jie ; Yan, Zixue ; Tang, Zilong ; Zhou, Le

Increasing the levels of antiapoptotic Bcl-2 proteins is an important way that cancer cells utilize to get out of apoptosis, underscoring their significance as promising targets for anticancer therapies. Lately, a primary compound 1 bearing thiazolidine-2,4-dione was discovered to exhibit comparable Mcl-1 inhibitory activity in comparison to WL-276. Herein, thirty-nine thiazolidine-2,4-dione analogs were yielded through incorporating different biphenyl moieties (R₁), amino acid side chains (R₂) and sulfonamides (R₃) on 1. The findings indicated that certain compounds exhibited favorable inhibitory effects against Bcl-2/Mcl-1, while demonstrating limited or negligible binding affinity towards Bcl-xL. In particular, compounds 16 and 20 exhibited greater Bcl-2/Mcl-1 inhibition compared to AT-101, WL-276 and 1. Moreover, they demonstrated notable antiproliferative effects and significantly induced apoptosis in U937 cells. The western blot and co-immunoprecipitation assays confirmed that 20 could induce alterations in the expression of apoptosis-associated proteins to result in apoptosis through on-target Bcl-2 and Mcl-1 inhibition. In addition, 20 exhibited favorable stability profiles in both rat plasma and rat liver microsomes. In total, 20 could be used as a promising compound to discover Bcl-2/Mcl-1 dual inhibitors with favorable therapeutic properties.

2

News (Medical) associated with R-(-)-Gossypol Acetic Acid

13 Jan 2025

·www.prnewswire.com

A28 Therapeutics and GATC Health Announce Comprehensive AI-Powered Analysis, Predicting Efficacy, Safety, and Potential Off-Target Effects of A28's AT-101 Cancer Drug Candidate

The analysis provides detailed insights to optimize clinical trial strategy, accelerate development, and de-risk decision-making. SAN FRANCISCO, Jan. 13, 2025 /PRNewswire/ -- A28 Therapeutics, Inc., a clinical stage biopharmaceutical company developing a novel platform technology for the treatment of multiple cancer types, today announced during the J.P. Morgan Healthcare Conference the completion of a comprehensive activity analysis for its AT-101 cancer drug candidate. This AI analysis by GATC Health Corp, a leader in AI-driven drug discovery, not only validates the potential of AT-101 but also provides A28 Therapeutics with a powerful tool to optimize its clinical trial strategy. By accurately assessing efficacy, safety, and potential off-target effects, the analysis provides actionable insights for reducing development risks, accelerating timelines, and lowering costs, paving the way for a more efficient path to clinical success. Continue Reading "GATC has set the standard in leveraging advanced AI to objectively analyze drug compounds to provide valuable insight into key endpoints, like mechanisms of action and toxicity, while exposing non-obvious areas of risk," explained Dr. Stanley Lewis, CEO of A28. "As an advisory board member since 2022, I have had direct access to the GATC team and understanding of the powerful toolset GATC uses to greatly de-risk research, development and financial decisions. This analysis provides an objective assessment of how our AT-101 drug candidate will perform in our next clinical trial." The analysis provides insights to optimize clinical trial strategy, accelerate development, and de-risk decision-making. Post this GATC's Multiomics Advanced Technology™ (MAT) AI platform performed in-silico experiments to determine the safety, efficacy and side-effect profile for A28's asset. Specifically, the MAT platform generated predictions for primary pharmacokinetics, bioaccumulation, toxicology, ADME considerations, adverse event analysis, side effects, endpoint matching, efficacy ratios, mechanisms of action, and immune response. "GATC Health's work with A28 demonstrates our ability to quickly provide deep insights and value into clinical-stage drug candidates utilizing the same technologies we employ for therapeutic discovery and early-stage development that can save years and tens of millions of dollars compared to traditional methods," noted Jayson Uffens, co-founder and CTO. "This collaboration showcases our value to empower leaders and researchers in biotech to accelerate their pre-clinical development and de-risk their clinical and fundraising efforts." A28 Therapeutics, Inc. A28 Therapeutics is a clinical stage biotechnology company developing first in class targeted oncolytic peptides (TOPs), for treatment of cancer. A28's lead candidate, AT-101, is currently being developed to treat hepatocellular carcinoma (HCC) leveraging its unique biodistribution that results in prolonged exposure in the liver. The immunologically favorable mechanism of tumor elimination provides for synergy with existing oncology medications including immune checkpoint inhibitors. To date, AT-101 has been tested in more than 75 patients where it demonstrated tolerability and remarkable anti-cancer activity. The A28 TOPs platform has produced a pipeline of products targeting multiple cancer types and cell receptors. For more information, please visit About GATC Health GATC Health Corp is a technology company revolutionizing drug discovery and development through its transformative AI platform and approach. The company's validated and proprietary Multiomics Advanced Technology™ (MAT) simulates human biochemistry's billions of interactions to rapidly create novel therapeutics, identify and confirm targets, accelerate development, and de-risk drug pipelines by predicting efficacy, safety, and off-target effects. For more information, please visit gatchealth.com SOURCE GATC Health; A28 Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

28 Jul 2023

·www.sciencedaily.com

Research points to potential new medical therapy for Lyme disease

A medical therapy that inhibits the growth of cancer cells may one day be effective at treating Lyme disease, according to new research study. A medical therapy that inhibits the growth of cancer cells may one day be effective at treating Lyme disease, according to new research by a University of Massachusetts Amherst team at the New England Regional Center of Vector-borne Diseases (NEWVEC). "It's a long way from something you're going to pick up at CVS, but these early findings are very encouraging," says vector-borne disease expert Stephen Rich, professor of microbiology, executive director of NEWVEC and senior author of the study published in the journal Pathogens. Lyme disease is the most common vector-borne disease in the U.S., spread by infected deer ticks. The potentially debilitating illness, which is diagnosed in about 476,000 people each year in the U.S., doesn't always respond to antibiotics. "There are people who have cases of Lyme disease that go on and on," Rich says. "So there's always interest in finding new therapies or new ways to inhibit the growth of the bacterium. And based on what we're seeing in the lab, this may be one of those ways." The discovery began with an "aha" moment by then-Ph.D. candidate Patrick Pearson, who was working in Rich's lab, along with graduate student Adam Lynch. Pearson, co-author of the paper, is now a NEWVEC post-doctoral researcher at UMass Amherst. Lynch, lead author, is now a research fellow in the Department of Veterinary and Animal Sciences. Tumor cells and Borrelia burgdorferi, the corkscrew-shaped bacterium that causes Lyme disease, share an unusual feature about the way they grow, Pearson noted and pondered. "It turns out that cancer cells and Borrelia both rely solely on glycolysis for their metabolism," Rich explains. Glycolysis, in turn, is dependent on one molecule called lactate dehydrogenase, or LDH. Pearson wondered whether LDH inhibitors, which are used as drug therapies to target certain cancers, might also be an effective strategy against Lyme disease. "It was a very clever idea," Rich says. "In principle, we thought these LDH inhibitors should work well to inhibit the growth of Lyme disease bacteria." And in fact, in in vitro experiments, they did. "…a range of commercially available LDH inhibitors with various mechanisms of action and origins were tested on Borrelia in Culture," the paper states. "Of these inhibitors, gossypol, AT-101, and oxamate substantially impacted B. burgdorferigrowth in vitro and represent promising candidates against Borrelia infections in vivo." Rich says the research will continue at NEWVEC, which was funded by the Centers for Disease Control and Prevention last year with a $10 million award to prevent and reduce tick- and mosquito-borne diseases in New England. NEWVEC aims to bring together academic communities, public health practitioners, residents and visitors across the Northeast, where Lyme infections are concentrated. "These experiments were done outside of hosts. Now we need to carry this out in mouse models and, eventually, in people," Rich says. The researchers note that this drug therapy may also be effective against another tick-borne disease, babesiosis, a malaria-like infection. "This has the potential to kill two birds with one stone," Rich says. "And that makes this discovery even more tantalizing."

100 Deals associated with R-(-)-Gossypol Acetic Acid

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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Endometriosis	China	Xian Epang Place Pharmaceutical Co. Ltd.	-

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glioblastoma Multiforme	Phase 2	China	Jiangsu Yasheng Pharmaceutical Development Co. Ltd.	20 Oct 2017
Non-Small Cell Lung Cancer	Phase 2	China	Ascentage Pharma Group International Co., Ltd.	02 Jun 2012
Non-Small Cell Lung Cancer	Phase 2	China	3SBio, Inc.	02 Jun 2012
Laryngeal Neoplasms	Phase 2	United States	Ascenta Therapeutics, Inc.	31 Mar 2012
Recurrent Squamous Cell Carcinoma of the Head and Neck	Phase 2	United States	Rogel Cancer Center: University of Michigan	01 Jun 2010
Advanced Lung Non-Small Cell Carcinoma	Phase 2	United States	Ascenta Therapeutics, Inc.	01 Sep 2009
Glioma	Phase 2	United States	Ascenta Therapeutics, Inc.	28 Feb 2009
Recurrent Non-Small Cell Lung Cancer	Phase 2	United States	Ascenta Therapeutics, Inc.	01 Sep 2007
Recurrent Non-Small Cell Lung Cancer	Phase 2	Russia	Ascenta Therapeutics, Inc.	01 Sep 2007
Recurrent Non-Small Cell Lung Cancer	Phase 2	Ukraine	Ascenta Therapeutics, Inc.	01 Sep 2007

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASH2023	Phase 1	B-cell lymphoma refractory	12	AT101	glzoujabqd(ewbgfelzbd) = pqmnteiaye wjnagfqbts (uujdrumgdt )	-	09 Dec 2023
NCT01003769 (CTgov)	Phase 1/2	Recurrent Chronic Lymphoid Leukemia	5	Lenalidomide	iztqoeqohh(mmhrauszxi) = hnbbqzknlw msipinancw (yjkyislfqk, nlhgozjyfu - qczecfeigu) View more	-	16 Jun 2020
NCT00891072 (Pubmed \| Invest New Drugs) Manual	Phase 1	Solid tumor	24	paclitaxel+carboplatin+AT-101	ceofpclvlp(wocllhzlmi) = the MTD was not determined pwppxsnyzw (jdekjfkdye )	Negative	01 Jun 2020
NCT02697344 (ASH 12019 \| ASH 22019) Manual	Phase 1	Relapse multiple myeloma	10	Lenalidomide+Dexamethasone+at-101	vxvqvxvgzo(tvneqeeckd) = at 20 mg daily dose of AT-101 with 25 mg of R and 40 mg weekly ：1 pt with febrile neutropenia and neutropenia lasting 9 days and 1 pt with thrombocytopenia lasting 8 days zesxvpbgis (fvbbxovrhk ) View more	Positive	13 Nov 2019
NCT00848016 (Pubmed \| Invest New Drugs) Manual	Phase 2	Adrenocortical Carcinoma	29	AT-101	aanqpdgfzn(duevrfozzo) = rcnivoaotv kvgonaxijx (hykbacvkls )	Negative	01 Aug 2019
NCT00540722 (CTgov)	Phase 2	Glioblastoma Multiforme \| Gliosarcoma \| Recurrent Glioblastoma	56	laboratory biomarker analysis+R-(-)-gossypol acetic acid	rconogdfbq(baplqgommz) = saewqnkstn qfacvechkz (pqawhmsokk, brvjysuuwc - eyguhqgfdc) View more	-	12 Jul 2017
NCT00988169 (CTgov)	Phase 2	Advanced Lung Non-Small Cell Carcinoma	6	erlotinib+AT-101	djukntfszm = linvbwigfr ewocsycwqz (imlqrckmyd, qsiapcxbdu - pfpzrbkxsh) View more	-	20 Nov 2015
NCT01285635 (CTgov)	Phase 2	Recurrent Squamous Cell Carcinoma of the Head and Neck	35	AT-101+Docetaxel	iqjvqznjzz = ajjqjwomcs rywexfzxbn (wpgqhgzpii, gkucgdocar - oinurhwmfj) View more	-	23 Jul 2015
NCT00666666 (CTgov)	Phase 2	Metastatic Prostate Carcinoma \| Adenocarcinoma of prostate	55	LHRH agent+AT-101+bicalutamide	ewerjgfuuz = lfzhdwutwx adyjbedvpv (aeqplgpcaw, captrctntf - wfcxigmvnd) View more	-	18 Dec 2014
NCT00848016 (CTgov)	Phase 2	Adrenocortical Carcinoma	29	R-(-)-gossypol acetic acid	pmjykqgsah = jdgosdqmbi rxmygmgwud (qqsmgqbenw, njcenewnzw - scruglawgq) View more	-	21 Feb 2014