Delving into the Latest Updates on CUDC-101 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

EGFR x HDACs x HER2

Action

antagonists, inhibitors

Mechanism

EGFR antagonists(Epidermal growth factor receptor erbB1 antagonists), HDAC inhibitors(Histone deacetylase inhibitors), HER2 antagonists(Receptor protein-tyrosine kinase erbB-2 antagonists)

Therapeutic Areas

NeoplasmsDigestive System DisordersRespiratory Diseases+ [1]

Active Indication-

Inactive Indication

Advanced Malignant Solid NeoplasmBreast CancerHead and Neck Neoplasms+ [4]

Originator Organization

Curis, Inc.

Active Organization-

Inactive Organization

Curis, Inc.

Drug Highest PhaseDiscontinuedPhase 1

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC24H26N4O4

InChIKeyPLIVFNIUGLLCEK-UHFFFAOYSA-N

CAS Registry1012054-59-9

The main purpose of this study is to determine the safety and tolerability of orally administered CUDC-101 in cancer patients, and to determine a dose for further testing. This study will also determine how well CUDC-101 is absorbed into the blood after being given orally, assess CUDC-101 blood levels and what happens to the study drug in the body, and study how the body reacts to the study drug and what effects it has on tumors. CUDC-101 has been administered to cancer patients as an intravenous (IV) infusion in other research studies, but has not been studied when given orally.

Start Date01 Sep 2012

Sponsor / Collaborator

Curis, Inc.

NCT01384799

/ CompletedPhase 1

A Phase I Dose Escalation Study to Investigate the Safety and Pharmacokinetics of Intravenous CUDC-101 With Concurrent Cisplatin and Radiation Therapy in Subjects With Locally Advanced Head and Neck Cancer

This is a phase I dose escalation study of CUDC-101 in combination with concurrent cisplatin and radiation therapy in patients with locally advanced head and neck cancer. CUDC-101 is a multi-targeted agent designed to inhibit epidermal growth factor receptor (EGFR), human epidermal growth factor receptor Type 2 (Her2) and histone deacetylase (HDAC). The study is designed to establish the safety, tolerability and maximum tolerated dose (MTD) of CUDC-101 when administered in combination with concurrent cisplatin and radiation over an 8-week treatment course, consisting of a one week run-in period of CUDC-101 administered alone, followed by seven weeks of combination treatment with CUDC-101, cisplatin and radiation therapy.

Start Date01 Nov 2011

Sponsor / Collaborator

Curis, Inc.

100 Clinical Results associated with CUDC-101

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100 Translational Medicine associated with CUDC-101

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100 Patents (Medical) associated with CUDC-101

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125

Literatures (Medical) associated with CUDC-101

01 Mar 2025·Virology

A high-throughput, microplate reader-based method to monitor in vitro HIV latency reversal in the absence of flow cytometry

Article

Author: Tietjen, Ian ; Liang, Kimberly ; Cassel, Joel ; Ntie-Kang, Fidele ; Montaner, Luis J ; Salvino, Joseph M ; Nkwelle, Chantal Emade ; Stephens, Unique ; Ndip, Roland N ; Esemu, Seraphine N

J-Lat cells are derivatives of the Jurkat CD4⁺ T cell line that contain a non-infectious, inducible HIV provirus with a GFP tag. While these cells have substantially advanced our understanding of HIV latency, their use by many laboratories in low and middle-income countries is restricted by limited access to flow cytometry. To overcome this barrier, we describe a modified J-Lat assay using a standard microplate reader that detects HIV-GFP expression following treatment with latency-reversing agents (LRAs). We show that HIV reactivation by control LRAs like prostratin and romidepsin is readily detected with dose dependence and with significant correlation and sensitivity to standard flow cytometry. For example, 10 μM prostratin induced a 20.1 ± 3.3-fold increase in GFP fluorescence in the microplate reader assay, which corresponded to 64.2 ± 5.0% GFP-positive cells detected by flow cytometery. Similarly, 0.3 μM prostratin induced a 1.7 ± 1.2-fold increase compared to 8.7 ± 5.7% GFP-positive cells detected. Using this method, we screen 79 epigenetic modifiers and identify CUDC-101, molibresib, and quisinostat as novel LRAs. This microplate reader-based method offers accessibility to researchers in resource-limited regions to work with J-Lat cells and more actively participate in global HIV cure research efforts.

05 Sep 2024·Journal of Computational Chemistry

GraphEGFR: Multi‐task and transfer learning based on molecular graph attention mechanism and fingerprints improving inhibitor bioactivity prediction for EGFR family proteins on data scarcity

Article

Author: Kinchagawat, Jiramet ; Rungrotmongkol, Thanyada ; Prommin, Chanatkran ; Yamprasert, Nattawin ; Kaewnuratchadasorn, Pawit ; Boonyarit, Bundit ; Nutanong, Sarana

AbstractThe proteins within the human epidermal growth factor receptor (EGFR) family, members of the tyrosine kinase receptor family, play a pivotal role in the molecular mechanisms driving the development of various tumors. Tyrosine kinase inhibitors, key compounds in targeted therapy, encounter challenges in cancer treatment due to emerging drug resistance mutations. Consequently, machine learning has undergone significant evolution to address the challenges of cancer drug discovery related to EGFR family proteins. However, the application of deep learning in this area is hindered by inherent difficulties associated with small‐scale data, particularly the risk of overfitting. Moreover, the design of a model architecture that facilitates learning through multi‐task and transfer learning, coupled with appropriate molecular representation, poses substantial challenges. In this study, we introduce GraphEGFR, a deep learning regression model designed to enhance molecular representation and model architecture for predicting the bioactivity of inhibitors against both wild‐type and mutant EGFR family proteins. GraphEGFR integrates a graph attention mechanism for molecular graphs with deep and convolutional neural networks for molecular fingerprints. We observed that GraphEGFR models employing multi‐task and transfer learning strategies generally achieve predictive performance comparable to existing competitive methods. The integration of molecular graphs and fingerprints adeptly captures relationships between atoms and enables both global and local pattern recognition. We further validated potential multi‐targeted inhibitors for wild‐type and mutant HER1 kinases, exploring key amino acid residues through molecular dynamics simulations to understand molecular interactions. This predictive model offers a robust strategy that could significantly contribute to overcoming the challenges of developing deep learning models for drug discovery with limited data and exploring new frontiers in multi‐targeted kinase drug discovery for EGFR family proteins.

01 Mar 2024·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

Raltitrexed induces apoptosis through activating ROS-mediated ER stress by impeding HSPA8 expression in prostate cancer cells

Article

Author: Li, Lanlan ; Sun, Jiaping ; Zhang, Jing ; Lu, Lanpeng ; Ma, Jialong ; Wang, Zhiping ; Fu, Shengjun ; Ma, Ruicong ; Tao, Yan ; Fu, Beitang ; Lu, Jianzhong ; Zhang, Shuni ; Liu, Shanhui

Prostate cancer is the most common malignant tumor in males, which frequently develops into castration-resistant prostate cancer (CRPC). CRPC metastasis is the main reason for its high mortality rate. At present, it lacks effective treatment for patients with CRPC. Raltitrexed (RTX) has been shown to be effective in the treatment of colorectal cancer. However, the effect of RTX on prostate cancer and the underlying mechanism remain unknown. In the current study, we found that RTX could dose-dependently inhibit proliferation, migration, colony formation and induce apoptosis in DU145 and PC-3 cells. RTX also increased ROS generation in prostate cancer cells. Pretreatment with N-acetyl-L-cysteine (NAC) significantly prevented RTX-induced cell apoptosis and endoplasmic reticulum (ER) stress signaling activation in prostate cancer cells. Additionally, we found RTX-induced ROS generation and ER stress activation depended on the expression of heat shock protein family A member 8 (HSPA8). Over-expression of HSPA8 could alleviate RTX-induced cell apoptosis, ROS generation and ER stress signaling activation. Finally, our study also showed that RTX attenuated the tumor growth of prostate cancer in the DU145 xenograft model and significantly downregulated HSPA8 expression and activated ER stress signaling pathway in tumor tissues. Our study is the first to reveal that RTX induces prostate cancer cells apoptosis through inhibiting the expression of HSPA8 and further inducing ROS-mediated ER stress pathway action. This study suggests that RTX may be a novel promising candidate drug for prostate cancer therapy.

100 Deals associated with CUDC-101

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12174

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Locally Advanced Malignant Neoplasm	Phase 1	United States	Curis, Inc.	01 Nov 2011
Breast Cancer	Phase 1	United States	Curis, Inc.	01 Jul 2010
Head and Neck Neoplasms	Phase 1	United States	Curis, Inc.	01 Jul 2010
Liver Cancer	Phase 1	United States	Curis, Inc.	01 Jul 2010
Non-Small Cell Lung Cancer	Phase 1	United States	Curis, Inc.	01 Jul 2010
Stomach Cancer	Phase 1	United States	Curis, Inc.	01 Jul 2010
Advanced Malignant Solid Neoplasm	Phase 1	United States	Curis, Inc.	01 Aug 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASTRO2013	Not Applicable	Glioblastoma Multiforme \| Breast Cancer	-	CUDC-101 0.5Î¼M	feezjkulpi(uqehljpeqd) = bjhrugdumz hmqigaekkc (cxfsnzihwh ) View more	-	01 Oct 2013
				CUDC-101 1.0Î¼M	feezjkulpi(uqehljpeqd) = bjddseclkn hmqigaekkc (cxfsnzihwh )