Delving into the Latest Updates on ENMD-2076 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

ENMD 2076, ENMD-981693, MKC-1693

Target

Aurora A x CSF-1R x FGFRs x FLT3 x VEGFR x c-Kit

Action

inhibitors, antagonists

Mechanism

Aurora A inhibitors(Serine/threonine-protein kinase Aurora-A inhibitors), CSF-1R antagonists(Colony stimulating factor 1 receptor antagonists), FGFRs antagonists(Fibroblast growth factor receptors antagonists)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication

ER positive, PR positive, HER2 positive breast cancerTriple Negative Breast Cancer

Inactive Indication

Acute Lymphoblastic LeukemiaAcute Myeloid LeukemiaAdvanced cancer+ [13]

Originator Organization

CASI Pharmaceuticals, Inc.

Active Organization

CASI Pharmaceuticals, Inc.

Alcami Carolinas Corp.

Inactive Organization-

License Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC25H31N7O6

InChIKeyKGWWHPZQLVVAPT-STTJLUEPSA-N

CAS Registry1453868-32-0

主要目的：通过三阴性乳腺癌受试者口服一定剂量的ENMD-2076，观察不良事件（AEs）发生的频率和严重程度，评估ENMD-2076的安全性和耐受性，在中国患者人群中确定合适剂量, 进而确定Ⅱb期临床试验治疗剂量。次要目的: 观察肿瘤变化和疾病进展，评价治疗的临床受益率。通过对肿瘤组织标本和血液样品进行基因外显子全序列的分析，评价其与ENMD-2076的药效相关性。

[Translation]

Primary purpose: To observe the frequency and severity of adverse events (AEs) by oral administration of a certain dose of ENMD-2076 to subjects with triple-negative breast cancer, evaluate the safety and tolerability of ENMD-2076, determine the appropriate dose in the Chinese patient population, and then determine the treatment dose for the Phase IIb clinical trial. Secondary purpose: To observe tumor changes and disease progression and evaluate the clinical benefit rate of treatment. By analyzing the full sequence of gene exons in tumor tissue specimens and blood samples, evaluate their correlation with the efficacy of ENMD-2076.

Start Date24 Mar 2015

Sponsor / Collaborator

Alcami Carolinas Corp.

[+2]

NCT01914510

/ CompletedPhase 2IIT

Phase II Study of Oral ENMD-2076 Administered to Patients With Ovarian Clear Cell Carcinomas

This is a phase 2 study to see how useful, safe, and tolerable an investigational drug called ENMD-2076 is in treating patients with ovarian clear cell carcinomas.
ENMD-2076 is an oral drug that works by blocking certain enzymes called Aurora A and tyrosine kinase from working. These enzymes are needed for cells to divide including cancer cells. ENMD-2076 also works by stopping the growth of new blood vessels which would provide the tumor with nutrients for it to grow. It is believed that by blocking Aurora A and tyrosine kinase enzymes from working and stopping new blood vessels from growing, the tumors may stop growing or shrink.

Start Date01 Sep 2013

Sponsor / Collaborator

University Health Network

100 Clinical Results associated with ENMD-2076

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100 Translational Medicine associated with ENMD-2076

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100 Patents (Medical) associated with ENMD-2076

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55

Literatures (Medical) associated with ENMD-2076

11 Sep 2025·JOURNAL OF MEDICINAL CHEMISTRY

Optimization of Novel Quinazolines as Potent Aurora Kinase Inhibitors for Triple-Negative Breast Cancer Treatment

Article

Author: Long, Zijie ; Cheng, Bao ; Zhai, Hongjin ; Lu, Gui ; Tu, Zhengchao ; Zhou, Huihao ; Long, Liang ; Liu, Quentin ; Peng, Wei ; Zhang, Bin ; Pan, Yujia

This work describes the discovery of a new series of Aurora kinase inhibitors based on quinazoline skeleton derived from ENMD-2076, as well as the first X-ray cocrystal structure complexes of vinyl-quinazoline 9h with Aurora A. Replacing pyrimidine with quinazoline improved anticancer activity and facilitated cocrystal formation. Compounds 9a and 9h showed excellent Aurora A kinase inhibition, with IC₅₀ values of 6.0 and 2.8 nM, respectively. 9h demonstrated superior activity against TNBC MDA-MB-231 cells with an IC₅₀ value of 48 nM and achieved 59% tumor growth inhibition in xenograft models, vs ENMD-2076's 33% with no observable toxicity. Mechanistic studies using immunoblotting, immunofluorescence staining, and flow cytometry showed that 9h outperforms ENMD-2076 in inhibiting Aurora A kinase activation, preventing spindle formation, arresting the cell cycle, and inducing cell apoptosis. Thus, 9h has the potential for further optimization and is a promising anticancer drug candidate.

01 Dec 2024·Letters in Drug Design & Discovery

Unlocking Therapeutic Potential: Molecular Docking Insights into Aurora Kinase A Inhibitors Patented and Published from 2011-2020 for Innovative Anticancer Drug Design

Author: Mazumder, Avijit ; Gupta, Manish K. ; Rani, Ketki ; Arora, Tripti

Background::

Enzymes belonging to the kinase family have been extensively implicated in cancer. Aurora A (AURKA) is crucial in regulating the cell cycle. AURKA's significant role in the formation of abnormal mitotic spindles and the failure of cytokinesis positions it as a promising target for anticancer treatments. Notably, AURKA is observed to be overexpressed in various cancer types, making its inhibition a compelling strategy for the development of anticancer agents.

Objective::

In this study, we set out to investigate a novel de novo design strategy aimed at developing and optimizing potent inhibitors for Aurora Kinase A. Given Aurora Kinase A's critical role in cell cycle regulation and its overexpression in various cancers, it presents a promising target for therapeutic intervention. Our goal was to create a new library of compounds, building on existing inhibitors known for their selectivity and potency against Aurora Kinase A. By making strategic modifications to these lead molecules, we aimed to improve their binding affinity and inhibitory effectiveness. This research was focused on identifying and refining compounds with enhanced drug-like properties and robust inhibitory potential, contributing to the advancement of effective anticancer therapies.

Methods::

A compound library based on known inhibitors having Aurora Kinase A selectivity and IC50 value in the nanomolar range was designed by modification in the lead molecules identified by analyzing the binding mode of the molecules in the catalytic site of the enzyme. A molecular docking study was performed in GOLD 2020. Drug-likeness ADME parameters (molecular weight, H-bond acceptors, H-bond donors, LogP, and the number of rotatable bonds) of designed molecules were calculated using SwissADME, pkCSM, and ProToxII web servers.

Results::

The docking study, utilizing GOLD 2020 software on Aurora Kinase A (PDB: 3W2C), successfully identified inhibitors that hindered the enzyme's activity by occupying its catalytic site. This inhibition mechanism, consistent across all cases, involves crucial interactions with residues such as Ala213, Asp274, and Phe144. A detailed analysis of the compounds guided the design of new analogs, aiming to enhance the lead compound's affinity for the receptor. Subsequent derivatization of M1 and M15 resulted in molecules (M1_46, M1_49, M1_50, M15_21, M15_14, and M15_43) showing a notable 10-15% increase in the Chemscore fitness scoring function compared to their parent molecules. This improvement correlated with a rise in the number of hydrogen bond interactions in the complexes, guiding further development.

Conclusion::

This computational assessment lays a foundation for further in-vitro and in-vivo studies in drug development, suggesting these derivatives as promising candidates for cancer treatment.

01 Dec 2024·Molecular diversity

Ligand-based pharmacophore modeling and machine learning for the discovery of potent aurora A kinase inhibitory leads of novel chemotypes

Article

Author: Safa Daoud ; Mutasem Omar Taha ; Rajaa Banat

Aurora-A (AURKA) is serine/threonine protein kinase involved in the regulation of numerous processes of cell division. Numerous studies have demonstrated strong association between AURKA and cancer. AURKA is overexpressed in many cancers, such as colon, breast and prostate cancers. Consequently, AURKA has emerged as promising target for therapeutic intervention in cancer management. Herein, we describe a computational workflow for the discovery of novel anti-AURKA inhibitory leads starting with ligand-based assessment of the pharmacophoric space of six diverse sets of inhibitors. Subsequently, machine learning/QSAR modeling was coupled with genetic function algorithm to search for the best possible combination of machine learner, ligand-based pharmacophore(s) and molecular descriptors capable of explaining variation in anti-AURKA bioactivities within a collected list of inhibitors. Two learners succeeded in achieving acceptable structure/activity correlations, namely, random forests and extreme gradient boosting (XGBoost). Three pharmacophores emerged in the successful ML models. These were then used as 3D search queries to mine the National Cancer Institute database for novel anti-AURKA leads. Top-ranking 38 hits were assessed in vitro for their anti-AURKA bioactivities. Among them, three compounds exhibited promising dose-response curves, demonstrating experimental IC₅₀ values ranging from sub-micromolar to low micromolar values. Remarkably, two of these compounds are of novel chemotypes.

2

News (Medical) associated with ENMD-2076

05 Feb 2010

·www.biospace.com

EntreMed, Inc. Raises Additional $2.5 Million In Registered Direct Offering

ROCKVILLE, Md., Feb. 4 /PRNewswire-FirstCall/ -- EntreMed, Inc. today announced that it completed a registered direct offering of 3,846,154 shares of its common stock, at a purchase price of $0.65 per share, to a single accredited institutional investor. The sale resulted in gross proceeds to the Company of $2.5 million. The terms of the purchase were set forth in a stock purchase agreement entered into by the parties on February 3, 2010. The per share purchase price reflects a 10% discount to the five-day average closing sale price ending on February 2, 2010. EntreMed plans to use the net proceeds of the offering, which are expected to be approximately $2.3 million after deducting the placement agent's fee and estimated offering expenses payable by EntreMed, to further clinical development of its Aurora A/angiogenic kinase inhibitor, ENMD-2076, and for other general corporate purposes. This press release does not and shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities, nor shall there be any sale of the securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any state. About EntreMed EntreMed, Inc. is a clinical-stage pharmaceutical company committed to developing primarily ENMD-2076, a selective angiogenic kinase inhibitor, for the treatment of cancer. ENMD-2076 is currently in Phase 1 studies in advanced cancers, multiple myeloma, and leukemia. The Company's other therapeutic candidates include MKC-1, an oral cell-cycle regulator with activity against the mTOR pathway currently in multiple Phase 2 clinical trials for cancer, and ENMD-1198, a novel antimitotic agent currently in Phase 1 studies in advanced cancers. The Company also has an approved IND application for Panzem(R) in rheumatoid arthritis. Additional information about EntreMed is available on the Company's web site at and in various filings with the Securities and Exchange Commission. CONTACT: Ginny Dunn, Associate Director, Corporate Communications & Investor Relations of EntreMed, Inc., +1-240-864-2643 Web site:

16 Oct 2007

·www.biospace.com

EntreMed, Inc. Appoints Senior Vice President of Research and Development Dr. Kenneth W. Bair Joins Senior Management Team

ROCKVILLE, Md., Oct. 16 /PRNewswire-FirstCall/ -- EntreMed, Inc. , a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, today announced that Kenneth W. Bair, Ph.D. has been appointed its Senior Vice President, Research and Development. Dr. Bair has also been elected an executive officer of EntreMed by the Board of Directors, reporting to James S. Burns, President & CEO. (Logo: ) Dr. Bair brings to EntreMed over 25 years of management experience in oncology drug discovery, development and chemistry. Prior to joining EntreMed, Dr. Bair served as Senior Vice President and Head, BioPharmaceuticals Research at Chiron Corporation in Emeryville, California. Prior to joining Chiron Corporation in 2003, Dr. Bair was Vice President, Discovery Oncology at Pharmacia Corporation in Peapack, New Jersey. From 1982 until joining Pharmacia, Dr. Bair held positions of increasing responsibility within the pharmaceutical industry, including Unit Head of Oncology at Novartis Pharmaceuticals Corporation and Executive Director and Head, Oncology Research Program, Sandoz Pharmaceuticals Corporation; and various oncology research positions at Burroughs Wellcome, Research Triangle Park, North Carolina. Dr. Bair received his Ph.D. in organic chemistry from Brandeis University, Waltham, Massachusetts, and was a Postdoctoral Fellow at the Massachusetts Institute of Technology, Cambridge, Massachusetts. Dr. Bair commented on his appointment at EntreMed, "I am delighted to be joining the EntreMed team. The Company has extensive scientific expertise in angiogenesis, cell cycle regulation, kinase inhibition and inflammation, which provide a strong foundation for building a leading oncology franchise. EntreMed's pipeline of HIF-1 alpha and kinase inhibitors fit well with my background and research interests. I look forward to leading the advancement of EntreMed's mechanism-based drugs for the treatment of cancer and inflammatory diseases." James S. Burns, EntreMed President & CEO commented, "I am very pleased to welcome Ken to EntreMed's leadership team. Ken joins EntreMed with a strong oncology research and development background in large pharmaceutical and biotech companies, experience that will be instrumental in leading EntreMed into its next phase of development." Mr. Burns continued, "Ken has a solid track record in identifying and developing oncology compounds. As Senior Vice President of Research and Development, Ken will play a critical role in leading the development of our ongoing research programs, prioritizing the existing portfolio, and identifying new compounds for our pipeline in order to select the best programs based on the strength of the data and their prospective competitive position." About EntreMed EntreMed, Inc. is a clinical-stage pharmaceutical company developing therapeutic candidates primarily for the treatment of cancer and inflammation. Panzem(R) NCD (2-methoxyestradiol or 2ME2) is currently in multiple Phase 2 clinical trials for cancer. MKC-1, an oral cell-cycle regulator, is in multiple Phase 1 and 2 studies for cancer. ENMD-1198, a novel tubulin-binding agent, is in Phase 1 studies in advanced cancers. Panzem(R) is also in preclinical development for rheumatoid arthritis, and ENMD-2076, a dual-acting Aurora-angiogenesis inhibitor, is in preclinical development for cancer. EntreMed's goal is to develop and commercialize new compounds based on the Company's expertise in angiogenesis, cell-cycle regulation and inflammation - processes vital to the treatment of cancer and other diseases, such as rheumatoid arthritis. Additional information about EntreMed is available on the Company's web site at and in various filings with the Securities and Exchange Commission. Forward Looking Statements This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act with respect to the outlook for expectations for future financial or business performance (including the timing of royalty revenues and future R&D expenditures), strategies, expectations and goals. Forward-looking statements are subject to numerous assumptions, risks and uncertainties, which change over time. Forward-looking statements speak only as of the date they are made, and no duty to update forward-looking statements is assumed. Actual results could differ materially from those currently anticipated due to a number of factors, including those set forth in Securities and Exchange Commission filings under "Risk Factors," including risks relating to the need for additional capital and the uncertainty of additional funding; variations in actual sales of Thalomid(R), risks associated with the Company's product candidates; the early-stage products under development; results in preclinical models are not necessarily indicative of clinical results, uncertainties relating to preclinical and clinical trials; success in the clinical development of any products; dependence on third parties; future capital needs; and risks relating to the commercialization, if any, of the Company's proposed products (such as marketing, safety, regulatory, patent, product liability, supply, competition and other risks). CONTACT: Ginny Dunn, Associate Director, Corporate Communications & Investor Relations of EntreMed, Inc., +1-240-864-2643 Web site:

100 Deals associated with ENMD-2076

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Hepatocellular Carcinoma	Phase 2	United States	CASI Pharmaceuticals, Inc.	01 Oct 2015
Fibrolamellar Hepatocellular Carcinoma	Phase 2	United States	CASI Pharmaceuticals, Inc.	01 Oct 2015
ER positive, PR positive, HER2 positive breast cancer	Phase 2	China	CASI Pharmaceuticals, Inc.	24 Mar 2015
ER positive, PR positive, HER2 positive breast cancer	Phase 2	China	Alcami Carolinas Corp.	24 Mar 2015
Triple Negative Breast Cancer	Phase 2	United States	CASI Pharmaceuticals, Inc.	01 Jul 2012
Triple Negative Breast Cancer	Phase 2	China	CASI Pharmaceuticals, Inc.	01 Jul 2012
Fallopian Tube Carcinoma	Phase 2	United States	CASI Pharmaceuticals, Inc.	01 Apr 2010
Fallopian Tube Carcinoma	Phase 2	Canada	CASI Pharmaceuticals, Inc.	01 Apr 2010
Peritoneal Neoplasms	Phase 2	United States	CASI Pharmaceuticals, Inc.	01 Apr 2010
Peritoneal Neoplasms	Phase 2	Canada	CASI Pharmaceuticals, Inc.	01 Apr 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02234986 (CTgov)	Phase 2	Advanced Hepatocellular Carcinoma \| Fibrolamellar Hepatocellular Carcinoma	35	ENMD-2076	evqajmczyq(qovipfpbdw) = fluwlaiezv gliztvofnr (roqrmbeojn, lywiqytena - abjrszpqxt) View more	-	18 Apr 2025
NCT02234986 (Pubmed \| Oncologist)	Phase 2	Fibrolamellar Hepatocellular Carcinoma DNAJB1-PRKACA gene fusion transcript RNA \| Aurora kinase A	35	ENMD-2076	gykcnuszdc(mduvtrkirb) = usfunabljk cyernalqhi (pkjelukhbm ) View more	Negative	01 Dec 2020
NCT01914510 (CTgov)	Phase 2	Ovarian clear cell adenocarcinoma	40	ENMD-2076	hklpjjhpnk = phpanknwpu tlrvmogkaf (pjjvywyuse, ylggpigkai - jvytfjowzh) View more	-	13 Dec 2019
NCT01719744 (Pubmed \| Sci Rep) Manual	Phase 2	Locally Advanced Soft Tissue Sarcoma First line PTPRB Mutation	25	ENMD-2076	htoledrttp(xbunfrmozf) = neehchpqul zhpgdwcggg (spicxtfgat, 3.2 - 38.4) View more	Negative	14 May 2019
NCT01639248 (Pubmed \| Clin Cancer Res \| Breast Cancer Res) Manual	Phase 2	Triple Negative Breast Cancer Second line triple-negative	41	ENMD-2076	yocleohdep(zymutxcawj) = qfpgskvycy nymyijuqvr (vaewhlukxs, 6 - 32.8)	Positive	02 Aug 2018
PD3-16 (SABCS2018)	Phase 2	Triple Negative Breast Cancer	41	ENMD-2076 250 mg	vdpfbovppt(irdyvtnzzz) = rmykzoprgq glcsotbvwz (mgzimlaiuv, 6% - 32.8%)	Positive	15 Feb 2018
NCT01719744 (CTgov)	Phase 2	Metastatic Soft Tissue Sarcoma	25	ENMD-2076	jfyyytjnhu = dyxkrkekbw jvktgztjmx (uwdynudnny, otxeieezlh - actjeqwwgl) View more	-	07 Nov 2017
NCT01914510 (ASCO2017)	Phase 2	Ovarian clear cell carcinoma	40	ENMD-2076	ggfpkcbijn(yqolrlbtja) = gftkljajga ozmxlmmgob (xutwfsdvgv, 3.4 - 4.4)	-	30 May 2017
Pubmed \| Invest New Drugs Manual	Phase 1	Acute Myeloid Leukemia \| Chronic Myelomonocytic Leukemia	27	ENMD-2076	jfhopbimrd(ugscjvagok) = 225 mg orally once daily zmrvzoskmk (abxuphaxbh ) View more	Positive	01 Oct 2016
NCT01914510 (ASCO2016)	Phase 2	Recurrent Ovarian Clear Cell Adenocarcinoma	32	ENMD-2076 275 mg	yrcqtktrio(zmqdcpaopa) = Drug-related adverse events (AEs) occurred in 24/28 (86%) evaluable pts, the most common being Grade (Gr) 1/2 fatigue, nausea/vomiting, hypertension and diarrhea. Gr ≥ 3 AEs were reported in 46% of pts. AE resulted in dose reductions in 11 pts (39%) and led to treatment discontinuation in 3. lpujwagori (nszdtktroo )	Positive	20 May 2016