Bcl-2 inhibitors(Apoptosis regulator Bcl-2 inhibitors), Bcl-xl inhibitors(Apoptosis regulator Bcl-X inhibitors), Mcl-1 inhibitors(Induced myeloid leukemia cell differentiation protein Mcl-1 inhibitors)

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication

Prostatic Cancer

Inactive Indication-

Originator Organization

University of Michigan

Active Organization

National Institutes of Health

Georgetown University Medical Center

University of Michigan

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC33H35NO6S

InChIKeyPQAPVTKIEGUPRN-UHFFFAOYSA-N

CAS Registry877877-35-5

100 Clinical Results associated with TW-37

100 Translational Medicine associated with TW-37

100 Patents (Medical) associated with TW-37

Literatures (Medical) associated with TW-37

01 Nov 2023·Archiv der Pharmazie

Repurposing of investigational cancer drugs: Early phase discovery of dengue virus NS2B/NS3 protease inhibitors

Article

Author: Saleem, Hafiza N ; Saeed, Muhammad ; Faisal, Amir ; Sohail, Iqra ; Jiskani, Ammar Hassan ; Kousar, Summara

AbstractDengue fever is a neglected vector‐borne disease and is more prevalent in Asia. Currently, no specific treatment is available. Given the time and cost of de novo drug discovery and development, an alternative option of drug repurposing is becoming an effective tool. We screened a library of 1127 pharmacologically active, metabolically stable, and structurally diverse small anticancer molecules to identify inhibitors of the dengue virus (DENV) NS2B/NS3 protease. Enzyme kinetics and inhibition data revealed four B‐cell lymphoma 2 inhibitors, that is, ABT263, ABT737, AT101, and TW37, as potent inhibitors of DENV NS2B/NS3 protease, with IC50 values of 0.86, 1.15, 0.81, and 0.89 µM, respectively. Mode of inhibition experiments and computational docking analyses indicated that ABT263 and ABT737 are competitive inhibitors, whereas AT101 and TW37 are noncompetitive inhibitors of the protease. With further evaluation, the identified inhibitors of the DENV NS2B/NS3 protease have the potential to be developed into specific anti‐dengue therapeutics.

01 Sep 2023·Genomics

Epigenetic alternations and targeted therapy in intrauterine adhesion: A comparative study

Article

Author: Gao, Linzhi ; Liang, Enming ; Li, Nan ; Chen, Shu ; Zhang, Xian ; Zhang, Dong ; Jiang, Guifang ; Wang, Xiaoyu ; Shen, Yuan ; Zhang, Ying

Although intrauterine adhesion (IUA) has been well recognized as a critical factor in infertility, little information is available regarding the molecular mechanisms. We performed a high-throughput RNA sequencing in the endometrium of three IUA patients and three normal controls. And another two gene expression profiles (PMID34968168 and GSE160365) were analyzed together. A total of 252 DEGs were identified. Cell cycle, E2F target, G2M checkpoint, integrin3 pathway and H1F1 signaling were aberrantly regulated in the IUA endometrium. 10 hub genes (CCL2, TFRC, THY1, IGF1, CTGF, SELL, SERPINE1, HBB, HBA1, LYZ) were exhibited in PPI analysis. FOXM1, IKBKB and MYC were three common transcription factors of DEGs. Five chemicals (MK-1775, PAC-1, TW-37, BIX-01294, 3-matida) were identified as putative therapeutic agents for IUA. Collectively, a series of DEGs associated with IUA were disclosed. Five chemicals and ten hub genes may be further explored as potential drugs and targets for IUA treatment.

01 Aug 2023·Experimental Eye Research

Retinal pigment epithelium exhibits gene expression and phagocytic activity alterations when exposed to retinoblastoma chemotherapeutics

Article

Author: Parulekar, Manoj ; Rozanska, Agata ; Benvenisty, Nissim ; Cerna-Chavez, Rodrigo ; Lako, Majlinda ; Poretti, Giulia Lodovica

Retinoblastoma (Rb) is a rare malignant disorder affecting the developing retina of children under the age of five. Chemotherapeutic agents used for treating Rb have been associated with defects of the retinal pigment epithelium (RPE), such as hyperplasia, gliosis, and mottling. Herein, we have developed two pluripotent stem cell (PSC)-RPE models to assess the cytotoxicity of known Rb chemotherapeutics such as Melphalan, Topotecan and TW-37. Our findings demonstrate that these drugs alter the RPE by decreasing the monolayer barrier's trans-epithelial resistance and affecting the cells' phagocytic activity. Transcriptional analyses demonstrate an altered expression of genes involved in melanin and retinol processing, tight junction and apical-basal polarity pathways in both models. When applied within the clinical range, none of the drug treatments caused significant cytotoxic effects, changes to the apical-basal polarity, tight junction network or cell cycle. Together, our results demonstrate that although the most commonly used Rb chemotherapeutic drugs do not cause cytotoxicity in RPE, their application in vitro leads to compromised phagocytosis and strength of the barrier function, in addition to changes in gene expression that could alter the visual cycle in vivo. Our data demonstrate that widely used Rb chemotherapeutic drugs can have a deleterious impact on RPE cells and thus great care has to be exercised with regard to their delivery so the adjacent healthy RPE is not damaged during the course of tumor eradication.

100 Deals associated with TW-37

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Prostatic Cancer	Preclinical	US	University of Michigan	12 Sep 2006
Prostatic Cancer	Preclinical	US	National Institutes of Health	12 Sep 2006
Prostatic Cancer	Preclinical	US	Georgetown University Medical Center	12 Sep 2006

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