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Merck
CN

SML4130

PFI-90

≥98% (HPLC)

Synonym(s):

2-Pyridinecarboxylic acid 2-(2-pyridinyl)hydrazide, KDM3B Inhibitor PFI-90, PAX3-FOXO1 transcriptional Inhibitor 90, N′-(Pyridin-2-yl)picolinohydrazide

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About This Item

Empirical Formula (Hill Notation):
C11H10N4O
CAS Number:
Molecular Weight:
214.22
MDL number:
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Quality Level

Assay

≥98% (HPLC)

form

powder

color

white to beige

solubility

DMSO: 2 mg/mL, clear

storage temp.

2-8°C

SMILES string

N(NC(=O)c2ncccc2)c1ncccc1
O=C(C1=NC=CC=C1)NNC2=NC=CC=C2

InChI

1S/C11H10N4O/c16-11(9-5-1-3-7-12-9)15-14-10-6-2-4-8-13-10/h1-8H,(H,13,14)(H,15,16)

InChI key

GCZPXNWBXDWHKM-UHFFFAOYSA-N

Biochem/physiol Actions

selective KDM3B inhibitor, disrupts PAX3-FOXO1 mediated transcription in FP-RMS.

PFI-90 directly targets and binds to metal ions in KDMs′ active sites, showing a strong preference for KDM3B (KD = 7.68 μM) while demonstrating minimal effect on other histone demethylases like KDM1A, KDM4B, KDM5A, KDM6B, HDAC1, HDAC2, HDAC3, and PRMT5. This selectivity leads to increased methylation at H3K4 and H3K9, disrupting the transcription of PAX3-FOXO1 oncogene targets in fusion-positive rhabdomyosarcoma (FP-RMS). PFI 90 effectively inhibits growth in PAX3-FOXO1 positive RMS cell lines (SCMC, RH4, RH30) with EC50 = 0.4, 0.9 and 3.2 µM, respectively. PFI-90 suppresses PAX3-FOXO1 function, inducing apoptosis and reducing RNA Pol2 activity without affecting PAX3-FOXO1 protein levels or DNA binding. Its treatment hampers FP-RMS tumor growth in vivo, offering a promising therapeutic avenue by selectively targeting KDM3B to combat FP-RMS.

Storage Class Code

11 - Combustible Solids

WGK

WGK 3

Flash Point(F)

Not applicable

Flash Point(C)

Not applicable

Regulatory Information

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KDM3B inhibitors disrupt the oncogenic activity of PAX3-FOXO1 in fusion-positive rhabdomyosarcoma
Nature Communications, 15(1), 1703-1703 (2024)

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