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Merck
CN

SML4109

PDK4-IN-1

≥98% (HPLC)

Synonym(s):

1-(1-(Piperidin-4-yl)-1H-pyrazol-4-yl)anthracene-9,10-dione hydrochloride, 1-[1-(4-Piperidinyl)-1H-pyrazol-4-yl]-9,10-anthracenedione hydrochloride

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About This Item

Empirical Formula (Hill Notation):
C22H19N3O2·HCl
CAS Number:
Molecular Weight:
393.87
MDL number:
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Quality Level

Assay

≥98% (HPLC)

form

powder

storage condition

desiccated

color

white to beige

solubility

H2O: 2 mg/mL, clear (Warmed)

storage temp.

-10 to -25°C

SMILES string

Cl.[n]2(ncc(c2)c3c4c(ccc3)C(=O)c5c(cccc5)C4=O)C1CCNCC1

InChI key

ZIMLKZKPNALXKK-UHFFFAOYSA-N

Biochem/physiol Actions

Potent, orally active PDK4 inhibitor with antidiabetic and anticancer efficacy.

PDK4-IN-1 (PDK4i-8c) is a cell-penetrating anthraquinone derivative that has been identified as an allosteric inhibitor of pyruvate dehydrogenase kinase 4 (PDK4), whis is binding to its lipoamide binding site with a high affinity (IC50 = 84 nM). PDK4-IN-1 is orally available, demonstrates excellent metabolic stability, and exhibits a promising pharmacokinetic profile in rat studies. Moreover, PDK4-IN-1 substantially enhances glucose tolerance in mice with diet-induced obesity and mitigates allergic reactions in a passive cutaneous anaphylaxis mouse model. The in vivo data support its effectiveness as a potential treatment for diabetes. Additionally, PDK4-IN shows notable anticancer properties by regulating cell proliferation, transformation, and apoptosis.

Disclaimer

Hygroscopic

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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Dahye Lee et al.
Journal of medicinal chemistry, 62(2), 575-588 (2019-01-10)
Pyruvate dehydrogenase kinase 4 (PDK4) activation is associated with metabolic diseases including hyperglycemia, insulin resistance, allergies, and cancer. Structural modifications of hit anthraquinone led to the identification of a new series of allosteric PDK4 inhibitors. Among this series, compound 8c
Mohammad Kasim Fatmi et al.
Aging cell, 22(4), e13800-e13800 (2023-02-18)
Ischemic heart disease (IHD) is the leading cause of death, with age range being the primary factor for development. The mechanisms by which aging increases vulnerability to ischemic insult are not well understood. We aim to use single-cell RNA sequencing
Xuefeng Dou et al.
Nature metabolism, 5(11), 1887-1910 (2023-10-31)
Senescent cells remain metabolically active, but their metabolic landscape and resulting implications remain underexplored. Here, we report upregulation of pyruvate dehydrogenase kinase 4 (PDK4) upon senescence, particularly in some stromal cell lines. Senescent cells display a PDK4-dependent increase in aerobic

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