Author: Hoang, Dinh Hoa ; Pirrotte, Patrick ; Kuo, Ya-Huei ; Pathak, Khyatiben ; Valerio, Melissa ; Graff, William ; Chen, Fang ; Kang, HyunJun ; Horne, David ; Marcucci, Guido ; Estrella, Katrina ; Zhang, Bin ; Xie, Jun ; Buettner, Ralf ; Nguyen, Le Xuan Truong ; Li, Zhuo ; Zhang, Lianjun

This is the first report on antileukemic activity of OST-01, a novel NP extracted from Baccharis coridifolia , on AML ′′ bulk " and LSC-enriched blasts.OST-01 treatment on dose dependent for 24 h significantly inhibits proliferation and colony formation and induces apoptosis in representative AML cell lines (MV-4-11, KG-1a, Kasumi-1 and HL-60), primary CD34 + CD38- blasts (enriched for LSCs; see Table S1 for mol. features), but not normal CD34 + CD38- mononuclear cells (MNCs) [enriched for hematopoietic stem cells (HSC)] (Fig. 1 A, B, Fig. S1), suggesting that OST-01 was cytotoxic to AML blasts, but spared normal HSCs.The oncogene MYC was among the top five downregulated genes and the gene set enrichment anal. (GSEA) indicated down-regulation of gene sets enriched for c-Myc targets, ribonucleoprotein complex, and ribosome biogenesis in OST-01 treated cells (Fig. S2A-D).A twenty-four-hour exposure to OST-01 resulted in a significantly decreased levels of c-Myc and o ther nucleolar proteins i.e., NPM1, nucleostemin and nucleolin, (Fig. 1 D, E and Fig. S2E) and disruption of the normal nucleolar architecture in HL-60 cells and CD34+CD38- AML blasts (Fig.1F and Fig. S2F).Accordingly, USP36 knock-down increased c-Myc and NPM1 ubiquitination (Fig. 1I). In contrast, USP36 overexpression rescued OST-01-induced c-Myc and NPM1 ubiquitination (Fig. 1J).To test OST-01 in vivo, 0.5 x 10 6 luciferase-expressing FLT3-ITD + Molm-13 AML cells (Luc-Molm13 cells) was injected into immunode fi cient NSG mice and treated them with either OST-01 or vehicle (ethanol) [1 μL/g, oral gavage, BID] until they achieved a euthanized endpoint (Fig. S4A).OST-01-treated mice demonstrated a significant reduction of the leukemia burden (Fig. 2 A) and increase of survival compared with vehicle-treated mice (Fig. S4B; p < 0.0001).They next tested the activity of OST-01 in combination with venetoclax (VEN), a selective BCL-2 inhibitor broadly used in combination with hypomethylating agents or other chemotherapeutics in AML patients [ 13 ], in CD34 + CD38- AML blasts.Compared with VEN or OST-01 alone, OST-01/VEN had synergistic antileukemic effects, as demonstrated by inhibition of proliferation and colony forming and increasing apoptosis (Fig. S7A-C).

Journal of Hematology & Oncology

Pharmacological activity of OST-01, a natural product from baccharis coridifolia, on breast cancer cells

Article

Author: Zhang, Bin ; Hoang, Dinh Hoa ; Pathak, Khyatiben ; Mortimer, Joanne ; Wu, Jun ; LeVee, Alexis ; Frankhouser, David ; Marcucci, Guido ; Valerio, Melissa ; LaBarge, Mark A ; Kang, HyunJun ; Nguyen, Le Xuan Truong ; Pirrotte, Patrick ; Rockne, Russell C ; Graff, William

AbstractNatural products have long been a viable source of therapeutic agents, providing unique structures and mechanisms that may be beneficial for cancer treatment. Herein we first report on the anticancer activity OST-01, a natural product from Baccharis Coridifolia, on breast cancer cells, including triple-negative breast cancer (TNBC). OST-01 significantly inhibited cell proliferation and oncogenic activities of TNBC cells in vitro. OST-01 also markedly inhibited TNBC tumor growth in vivo, with > 50% reduction in tumor size compared to vehicle control treatment in different in vivo models, i.e., cell line-derived (CDX), patient-derived (PDX), and mammary fat pad xenografts. Mechanistically, OST-01 induces ferroptosis by downregulating LRP8-regulated selenoproteins, i.e., GPX4. A shift from a basal-mesenchymal to a luminal-epithelial state of breast cancer stem cells (BCSCs) as supported by the downregulation of stemness (e.g., CD44) and mesenchymal (e.g., FN1 and vimentin) markers, along with the upregulation of differentiation markers (e.g., CD24) and luminal-epithelial markers (e.g., CK19), was also observed.

News (Medical) associated with OST-01

31 May 2023

·www.biospace.com

Ostentus Therapeutics, Inc., and City of Hope to Continue Studies of Novel OST Natural Products for Treatment of Leukemia and Other Cancers

NEWPORT BEACH, Calif.--(BUSINESS WIRE)-- Ostentus Therapeutics, Inc., announced today that it has entered into a second Sponsored Research Agreement with City of Hope, one of the largest cancer research and treatment organizations in the United States, to conduct preclinical research on OST compounds, which could be used as future therapies for leukemia and other cancers. OST compounds are natural products derived from plants native of tropical and subtropical America, which have been used in alternative and traditional medicine. At City of Hope, these compounds will undergo rigorous pharmacologic and preliminary toxicologic testing at specialized laboratories. The compounds’ active principles will be investigated individually and in combination to identify their mechanisms of action and anticancer activity. Guido Marcucci, M.D., director of City of Hope’s Gehr Family Center for Leukemia Research, chair of the Department of Hematologic Malignancies Translational Science, part of City of Hope’s Comprehensive Cancer Center, and chief of its Division of Leukemia Research, will lead the research, which is expected to culminate in a first-in-human clinical trial. “Ostentus is honored to continue working with City of Hope and Dr. Marcucci on this exciting new phase in the journey of bringing OST proprietary compounds to the market as a potential anti-cancer therapy,” said William Graff, Ostentus co-founder and director. “We have been pleased working with Ostentus on this exciting project and the potential application of the OST natural products (OST-01) to our personalized therapeutic approaches for cancer and leukemia patients,” Marcucci added. The anti-cancer activity of OST-01 has now been demonstrated in leukemia, glioblastoma, lung, colorectal, triple negative breast, ovarian, and pancreatic cancers both in vitro and in vivo. The mechanism of action through which OST-01 significantly inhibits cancer cells has also been explored broadly. These results provide strong evidence that OST-01 targets both leukemic and cancer stem cells by suppressing predominant upregulated “stemness” signaling. Importantly, OST-01 safety has been demonstrated by the lack of non-toxic and non-adverse health effects on both normal and cancer mouse models. Ostentus is making important progress in identifying the principal molecule(s) with anti-cancer activity in the OST-01 plant extract. By employing analytical chromatography [e.g., high-performance liquid chromatography (HPLC), liquid chromatography ultraviolet and mass spectrometry (LC-UV and LC-MS)], the bioactive fractions of OST-01 have been isolated and are undergoing rigorous evaluation to confirm their individual anti-cancer activity. About Ostentus Therapeutics Ostentus Therapeutics, Inc. is a biotechnology company investigating the activity, efficacy and safety of novel natural compounds in the treatment of different types of cancer and leukemia through rigorous pharmacological testing. View source version on businesswire.com: Contacts William Graff 714.658.8866 w.graff@ostentustherapeutics.com Source: Ostentus Therapeutics, Inc. View this news release online at:

100 Deals associated with OST-01

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Colorectal Cancer	Preclinical	United States	Ostentus Therapeutics, Inc.	31 May 2023
Glioblastoma	Preclinical	United States	Ostentus Therapeutics, Inc.	31 May 2023
Leukemia	Preclinical	United States	Ostentus Therapeutics, Inc.	31 May 2023
Lung Cancer	Preclinical	United States	Ostentus Therapeutics, Inc.	31 May 2023
Ovarian Cancer	Preclinical	United States	Ostentus Therapeutics, Inc.	31 May 2023
Triple Negative Breast Cancer	Preclinical	United States	Ostentus Therapeutics, Inc.	31 May 2023

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

OST-01

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation