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Chemical Structure| 2569009-58-9 Chemical Structure| 2569009-58-9

Structure of PF-9363
CAS No.: 2569009-58-9

Chemical Structure| 2569009-58-9

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PF-9363 (CTx-648) is a highly efficient and selective KAT6A/KAT6B inhibitor. It can be used in cancer research.

Synonyms: CTx-648

4.5 *For Research Use Only !

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Product Citations

Product Citations

Shuling Han ; Zhuo Chen ; Chang Hong ; Tianjiao Dang ; Futing Bai ; Yuli Ruan , et al.

Abstract: The tumor microenvironment of colorectal cancer (CRC) exhibits a highly immunosuppressive phenotype, contributing to resistance against immunotherapy and poor prognosis in patients. Lysine acetyltransferase 6A (KAT6A) is significant in immune regulation and advanced breast cancer treatment. However, its mechanistic involvement in regulating immune responses in CRC remains unclear. Using clinical CRC cohorts, we evaluated KAT6A expression levels and their clinical significance in this study. We investigated its functional role through subcutaneous and metastatic in mice. Our findings demonstrate that KAT6A is overexpressed in CRC and correlates with poor prognosis. Mass cytometry (CyTOF) and ATAC-seq analyses revealed that KAT6A knockdown enhanced CD8+ T cell infiltration by activating interferon (IFN) signaling pathways. Gene Set Enrichment Analysis (GSEA) and immunofluorescence assays confirmed that KAT6A knockdown activates the cGAS-STING pathway, subsequently inducing IFN-mediated immune responses. Mechanistically, knockdown of KAT6A relieves c-MYC/DNMT1-mediated repression of cGAS. We also evaluated the therapeutic effects of a KAT6A inhibitor alone and its combination with anti-PD-1 in microsatellite stable (MSS) and microsatellite instability-high (MSI-H) mouse models, demonstrating synergistic efficacy in combination therapy. Furthermore, in a cohort of CRC patients receiving immunotherapy, we showed that high KAT6A expression correlated with impaired treatment response, manifested by lower objective response rates, shorter progression-free survival (PFS), and decreased overall survival (OS). Importantly, this study reveals KAT6A’s pivotal role in modulating CRC immune evasion via regulating endogenous IFN response of tumor cells, thereby establishing its potential as a therapeutic target for enhancing immunotherapy efficacy in CRC.

Keywords: Colorectal cancer ; KAT6A inhibitor ; Innate immunity ; CD8+ T cells ; Immunotherapy resistance

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Product Details of PF-9363

CAS No. :2569009-58-9
Formula : C20H20N4O6S
M.W : 444.46
SMILES Code : O=S(C1=C(OC)C=CC=C1OC)(NC2=NOC3=C2C(OC)=CC(CN4N=CC=C4)=C3)=O
Synonyms :
CTx-648
MDL No. :N/A

Safety of PF-9363

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Related Pathways of PF-9363

epigenetics

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
mouse SCLC cell line 1014 100 nM 6 days Inhibit KAT6A/KAT6B activity and evaluate the effect on NEUROD1 expression Nat Cell Biol. 2023 Sep;25(9):1346-1358.

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2.25mL

0.45mL

0.22mL

11.25mL

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1.12mL

22.50mL

4.50mL

2.25mL

 

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