Table 1.
The preclinical research related to THZ1 in the treatment of different types of cancers.
| Authors & year | Cancer type | Investigation methods | Proposed mechanisms |
|---|---|---|---|
| Kwiatkowski et al. 20146 | T-ALL | Resazurin based assay; GO term enrichment analysis; ChIP-seq analysis; bioluminescent images; gene set enrichment analysis; in vitro & in vivo assay | Downregulation of the RUNX1-driven transcriptional program |
| Chipumuro et al. 201426 | NB | Cell-cycle analysis; apoptosis analysis; immunohistochemical analysis; immunoblot analysis; qRT-PCR analysis; ChIP-qPCR analysis; ChIP-seq analysis; in vitro & in vivo assay | THZ1 targets the expression of both MYCN and MYCN-driven transcription amplification |
| Christensen et al. 201443 | SCLC | High-throughput small-molecule screen; MRI quantification; immunoblot analysis; proliferation assay; GO term enrichment analysis; ChIP-seq analysis; in vitro & in vivo assay | Downregulation of ASCL1, INSM1 and other oncogenetic transcription factors |
| Wang et al. 201550 | TNBC | Cell viability assay; immunoblot analysis; chemical molecular modification; drug in vivo stability analysis; H&E staining of tissue sections; gene set enrichment analysis; microarray expression analysis; quantitative PCR analysis; CRISPR/Cas9-mediated gene editing; in vitro & in vivo assay | Inhibition of CDK7 downregulates super-enhancer mediated oncogene transcription |
| Cayrol et al. 201754 | PTCL | Immunohistochemical analysis; immunoblot analysis; cell viability assay (Resazurin based); gene set enrichment analysis; Q-ChIP analysis; qRT-PCR analysis; response-surface analysis; RNA sequencing; in vitro & in vivo assay | THZ1 downregulates STAT-signaling dependent actively transcribed genes |
| Zeng et al. 201820 |
Ovarian cancer | CRISPR/Cas9-mediated gene editing; immunoblot analysis; qRT-PCR analysis; gene set enrichment analysis; cell proliferation assays; RNA sequencing; in vitro & in vivo assay | Downregulation of MYC and MCL1 which requires both CDK7 and CDK 12/13 inhibition |
| Cheng et al. 201846 | NSCLC | Cell proliferation assay; wound-healing assay; qRT-PCR analysis; immunoblot analysis; cell-cycle analysis; apoptosis analysis | THZ1 induced cell cycle arrest; blocked the glycolysis pathway; promoted ubiquitination and degradation of NUDT21 |
| Ning et al. 201967 | Cervical cancer and retinoblastoma | Cell-cycle analysis; apoptosis analysis; RT-PCR analysis; Immunoblot analysis; RNA sequencing; In vitro & in vivo assay | THZ1 prevents TGFβ2-induced EMT in human LECs;THZ1 inactivates the MAPK, ERK1/2 and PI3K/AKT signaling pathways; THZ1 caused cell-cycle arrest |
| Lu et al. 201968 | PDAC | Cell viability assay; apoptosis analysis; cell-cycle analysis; immunoblot analysis; immunohistochemical analysis; H&E staining of tissue sections; GO term enrichment analysis; RNA sequencing; in vitro & in vivo assay | THZ1 caused cell-cycle arrest; THZ1 inhibites TNF/NF-κB signaling pathway; THZ1 downregulates Hippo, MAPK signaling pathways |
T-ALL: T-cell acute lymphoblastic leukaemia; GO: gene ontology; ChIP-seq: chromatin immunoprecipitation coupled with high-throughput sequencing; RUNX1: Runt-related transcription factor 1; NB: neuroblastoma; qRT-PCR: quantitative real-time polymerase chain reaction; PCR: polymerase chain reaction; CHIP-qPCR: chromatin Immunoprecipitation-quantitative PCR; SCLC: small-cell lung cancer; MRI: magnetic resonance imaging; ASCL1: achaete-scute homolog 1; INSM1: insulinoma-associated 1; TNBC: triple-negative breast cancer; H & E: hematoxylin-eosin; CRISPR: clusters of regularly interspaced short palindromic repeats; Cas9: CRISPR associated protein 9; CDK7: cyclin-dependent kinase 7; PTCL: peripheral T-cell lymphomas; Q-ChIP: fast chromatin immunoprecipitation assay; RT-PCR: real-time PCR; RNA: ribonucleic acid; STAT: signal transducers and activators of transcription; NSCLC: non-small-cell lung cancer; NUDT21: nudix-type motif 21; RT-PCR: real-time PCR; TGFβ2: transforming growth factor beta 2; EMT: epithelial-to-mesenchymal transition; LECs: lens epithelial cells; ERK1/2: extracellular signal-regulated kinase1/2; PI3K: phosphatidylinositol 3-kinases; AKT: protein kinase B; PDAC: pancreatic ductal adenocarcinoma; TNF: tumor necrosis factor; NF-κB: nuclear factor-κB; MAPK: mitogen-activated protein kinase.