Kdm4-IN-4
[CAS# 2230475-63-3]

Identification

• Classification: Biochemical >> Amino acids and their derivatives >> Lysine derivative
• Name: Kdm4-IN-4
• Synonyms: (1R,2S,3R,4S)-3-[(dimethylamino)methyl]-1-phenylbicyclo[2.2.1]heptan-2-ol
• Molecular Formula: C₁₆H₂₃NO
• Molecular Weight: 245.36
• CAS Registry Number: 2230475-63-3
• SMILES: CN(C)C[C@H]1[C@H]2CC[C@](C2)([C@H]1O)C3=CC=CC=C3

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 356.2±25.0 ºC 760 mmHg (Calc.)^*
• Flash point: 159.9±21.8 ºC (Calc.)^*
• Index of refraction: 1.579 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Discovory and Applicatios

Kdm4-IN-4 is a small-molecule inhibitor targeting the lysine demethylase 4 (KDM4) family of enzymes, which are part of the Jumonji C (JmjC) domain-containing histone demethylases. KDM4 enzymes play a key role in epigenetic regulation by demethylating specific lysine residues on histone proteins, particularly histone H3 on lysines 9 and 36 (H3K9me3/me2 and H3K36me3/me2). This demethylation modulates chromatin structure and gene expression, impacting various cellular processes including DNA repair, cell proliferation, and differentiation.

The discovery of Kdm4-IN-4 stems from a growing interest in epigenetic regulators as therapeutic targets for cancer and other diseases involving aberrant gene expression. Dysregulation of KDM4 activity has been linked to tumor progression, metastasis, and poor prognosis in multiple cancers, making selective inhibitors like Kdm4-IN-4 valuable tools for both research and potential clinical applications.

Kdm4-IN-4 exhibits high potency and selectivity toward KDM4 isoforms, effectively blocking their demethylase activity. By inhibiting KDM4 enzymes, Kdm4-IN-4 promotes accumulation of methyl marks on histones, leading to altered transcriptional profiles that can suppress oncogenic pathways. Preclinical studies have demonstrated that Kdm4-IN-4 can induce cell cycle arrest and apoptosis in cancer cell lines dependent on KDM4 activity.

In addition to oncology, Kdm4-IN-4 serves as an important chemical probe to dissect the biological roles of KDM4 enzymes in normal physiology and disease states. Its use in cellular and animal models has expanded understanding of how histone methylation dynamics influence chromatin remodeling and gene regulation.

The development of Kdm4-IN-4 reflects the broader strategy of targeting epigenetic modifiers for therapeutic intervention. Its pharmacological profile includes favorable potency, selectivity, and cellular activity, supporting further evaluation in disease models where KDM4 contributes to pathogenesis.

Kdm4-IN-4 represents a promising lead compound for epigenetic drug discovery and offers a valuable tool for investigating the therapeutic potential of KDM4 inhibition in cancer and possibly other disorders characterized by epigenetic dysregulation.

References

2022. Recent Advances with KDM4 Inhibitors and Potential Applications. Journal of Medicinal Chemistry, 65(14).
DOI: 10.1021/acs.jmedchem.2c00680