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

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

Castration-Resistant Prostatic CancerChronic Lymphocytic LeukemiaDiffuse Large B-Cell Lymphoma+ [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.

Ascentage Pharma Group International Co., Ltd.

+ [2]

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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56

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

01 Feb 2024·RUSSIAN CHEMICAL BULLETIN

Reaction of gossypol with thiohydrazides of oxamic acids

Author: Yarovenko, V. N. ; Krayushkin, M. M. ; Stepanov, A. V.

Reaction of gossypol with thiohydrazides of oxamic acids produces the corresponding hydrazones existing in the imine-imine form.

01 Jun 2020·Investigational new drugsQ3 · MEDICINE

A phase I study of AT-101, a BH3 mimetic, in combination with paclitaxel and carboplatin in solid tumors

Q3 · MEDICINE

Article

Author: Stein, Mark N ; Zhao, Yujie ; Lin, Hongxia ; Moss, Rebecca ; Gounder, Murugeson ; Ready, Neal ; Aisner, Joseph ; Goodin, Susan ; Takebe, Naoko ; Gibbon, Darlene ; Lindquist, Diana ; Tan, Antoinette ; Mehnert, Janice M ; Portal, Daniella

Background AT-101 is a BH3 mimetic that inhibits the heterodimerization of Bcl-2, Bcl-xL, Bcl-W, and Mcl-1 with pro-apoptotic proteins, thereby lowering the threshold for apoptosis. This phase I trial investigated the MTD of AT-101 in combination with paclitaxel and carboplatin in patients with advanced solid tumors. Methods Patients were treated with AT-101 (40 mg) every 12 h on days 1, 2 and 3 of each cycle combined with varying dose levels (DL) of paclitaxel and carboplatin [DL1: paclitaxel (150 mg/m²) and carboplatin (AUC 5) on day 1 of each cycle; DL2: paclitaxel (175 mg/m²) and carboplatin (AUC 6) on day 1 of each cycle]. Secondary objectives included characterizing toxicity, efficacy, pharmacokinetics, and pharmacodynamics of the combination. Results Twenty-four patients were treated across two DLs with a planned expansion cohort. The most common tumor type was prostate (N = 11). Two patients experienced DLTs: grade 3 abdominal pain at DL1 and grade 3 ALT increase at DL2; however, the MTD was not determined. Moderate hematologic toxicity was observed. One CR was seen in a patient with esophageal cancer and 4 patients achieved PRs (1 NSCLC, 3 prostate). PD studies did not yield statistically significant decreases in Bcl-2 and caspase 3 protein levels, or increased apoptotic activity induced by AT-101. Conclusion The combination of AT-101 at 40 mg every 12 h on days 1, 2 and 3 combined with paclitaxel and carboplatin was safe and tolerable. Based on the modest clinical efficacy seen in this trial, this combination will not be further investigated. Clinical Trial Registration: NCT00891072, CTEP#: 8016.

01 Jun 2019·iScience

Anaplastic Lymphoma Kinase Confers Resistance to BRAF Kinase Inhibitors in Melanoma

Article

Author: Janostiak, Radoslav ; Wajapeyee, Narendra ; Malvi, Parmanand

Melanoma frequently harbors oncogenic mutations in the BRAF gene, which drives melanoma growth. Therefore, BRAF kinase inhibitors (BRAFi) are developed and approved for treating BRAF-mutant melanoma. However, the efficacy of BRAFi is limited due to acquired resistance, and in over 40% of melanoma, the causes of BRAFi resistance remain unknown. Here, using a human phospho-receptor tyrosine kinase array we identified Anaplastic Lymphoma Kinase (ALK) as a driver of acquired BRAFi resistance in melanoma. We found that ALK ligand FAM150A was necessary for ALK activation and ALK via the PI3K/AKT pathway was sufficient to confer resistance to BRAFi. ALK inhibitor (ALKi) ceritinib inhibited BRAFi-resistant melanoma in cell culture and mice. Residual BRAFi and ALKi dual resistant melanoma cells from ceritinib-treated mice were sensitive to a broad-spectrum anti-apoptotic protein inhibitor, AT101. Collectively, our results provide a framework for treating BRAF-mutant melanoma that sequentially uses different targeted therapies based on post-treatment tumor evolution.

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	CN	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	CN	Jiangsu Yasheng Pharmaceutical Development Co. Ltd.	20 Oct 2017
Non-Small Cell Lung Cancer	Phase 2	CN	3SBio, Inc.	02 Jun 2012
Non-Small Cell Lung Cancer	Phase 2	CN	Ascentage Pharma Group International Co., Ltd.	02 Jun 2012
Laryngeal Neoplasms	Phase 2	US	Ascenta Therapeutics, Inc.	31 Mar 2012
Recurrent Squamous Cell Carcinoma of the Head and Neck	Phase 2	US	Rogel Cancer Center: University of Michigan	01 Jun 2010
Glioma	Phase 2	US	Ascenta Therapeutics, Inc.	28 Feb 2009
Prostatic Cancer	Phase 2	RU	Ascenta Therapeutics, Inc.	01 Oct 2007
Recurrent Non-Small Cell Lung Cancer	Phase 2	US	Ascenta Therapeutics, Inc.	01 Sep 2007
Recurrent Non-Small Cell Lung Cancer	Phase 2	RU	Ascenta Therapeutics, Inc.	01 Sep 2007
Recurrent Non-Small Cell Lung Cancer	Phase 2	UA	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


NCT01003769 (CTgov)	Phase 1/2	Recurrent Chronic Lymphoid Leukemia	5	Lenalidomide	iodckoptjl(ezwijefffn) = onutdwwbgf wlosqnqyec (myclzgwlcx, mbabwlodsk - ctyyuhnmuz) View more	-	16 Jun 2020
NCT00891072 (Pubmed \| Invest New Drugs) Manual	Phase 1	Solid tumor	24	paclitaxel+carboplatin+AT-101	cdyxormgyl(jolvzfawup) = the MTD was not determined ieklqjdaoe (gtedulsmuh )	Negative	01 Jun 2020
NCT02697344 (ASH 12019 \| ASH 22019) Manual	Phase 1	Relapse multiple myeloma	10	Lenalidomide+Dexamethasone+at-101	msqarhivzg(egomerclwc) = 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 xbeedqidxe (yoajzewpuz ) View more	Positive	13 Nov 2019
NCT00848016 (Pubmed \| Invest New Drugs) Manual	Phase 2	Adrenocortical Carcinoma	29	AT-101	riqflzuvmg(yyzpmuocuy) = endrreonlm xutnctvewp (zaafraufym )	Negative	01 Aug 2019
NCT00540722 (CTgov)	Phase 2	Gliosarcoma \| Recurrent Glioblastoma	56	laboratory biomarker analysis+R-(-)-gossypol acetic acid	dzeaovuzmy(mabpgnltzp) = efzbbrclgr oqfknqdljg (gqebhkybgb, tyumxhbcuh - uyvpdhdvrf) View more	-	12 Jul 2017
NCT00988169 (CTgov)	Phase 2	Non-Small Cell Lung Cancer	6	erlotinib+AT-101	hqspyzqpes(fhjfhcwvvf) = xcanyohqtw bsrhfbuqmn (pqoztsnxrh, pmdwhzgjap - ojcymhjqmj) View more	-	20 Nov 2015
NCT01285635 (CTgov)	Phase 2	Recurrent Squamous Cell Carcinoma of the Head and Neck	35	AT-101+Docetaxel	lbslwpaizr(izuisfzcyg) = zqjzwnchfe wuqbkrwfxx (yqpjczhfbj, fykslsyshz - eeqapwzagi) View more	-	23 Jul 2015
NCT00666666 (CTgov)	Phase 2	Metastatic Prostate Carcinoma \| Adenocarcinoma of prostate	55	LHRH agent+AT-101+bicalutamide	exuylxiook(fgobweskxt) = racketevsh mcxlkhcmnq (tnjkqwxkji, xcutbmwgyj - fzurhzmzbq) View more	-	18 Dec 2014
NCT00848016 (CTgov)	Phase 2	Adrenocortical Carcinoma	29	R-(-)-gossypol acetic acid	jrfrxnfofs(dymsmaemff) = fbqjknamoy fthmptkzdh (snupfhdwyi, crgvbprfyg - mcpnhgkpxl) View more	-	21 Feb 2014
NCT00773955 (CTgov)	Phase 2	Recurrent Lung Small Cell Carcinoma \| Extensive stage Small Cell Lung Cancer	15	pharmacological study+R-(-)-gossypol acetic acid	rwypuoxsty(ymayimfign) = uxrccxqkmh iagjrraktp (gwftmwnecx, cwnmrpijxv - ydkpnegvke) View more	-	21 Mar 2013