PD 0325901 Chemical Properties

Melting point:

112-114°C

Density 

1.817±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: soluble20mg/mL, clear

form 

White to off-white solid

pka

13.45±0.20(Predicted)

color 

white to off-white

optical activity

[α]/D -1.8 to -3.5°, c = 1 mg/mL in methanol

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months.

InChI

InChI=1S/C16H14F3IN2O4/c17-11-3-2-10(16(25)22-26-7-9(24)6-23)15(14(11)19)21-13-4-1-8(20)5-12(13)18/h1-5,9,21,23-24H,6-7H2,(H,22,25)/t9-/m1/s1

InChIKey

SUDAHWBOROXANE-SECBINFHSA-N

SMILES

C(NOC[C@H](O)CO)(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F

Safety Information

Hazard Codes 

T,N

Risk Statements 

25-48-50

Safety Statements 

22-36/37/39-61

RIDADR 

UN 2811 6.1 / PGIII

WGK Germany 

3

HazardClass 

IRRITANT

HS Code 

29242990

PD 0325901 Usage And Synthesis

Description

PD 325901 (391210-10-9) is a selective non-ATP competitive MEK inhibitor (IC50 = 0.33 nM).1 Inhibits growth and/or proliferation of a variety of cancer cells.2 Enhances self-renewal of embryonic stem cells.3 In combination with vitamin C, synergistically induces hypomethylation of mouse embryonic stem cells.4 In combination with CHIR-99021 and A83-01 induces generation of ground state iPS cells from human and rat somatic cells.5

Chemical Properties

White to Off-White Solid

Uses

PD 0325901 has been used as an inhibitor in extracellular signal-regulated kinase (ERK) inhibition assay in primed induced pluripotent stem cells, RKO colorectal cancer cell line and human embryonic stem cells(hESCs).

Uses

The mitogenic extracellular kinase 1/2 (MEK1/2) inhibitor

Definition

ChEBI: A hydroxamic acid ester that is benzhydroxamic acid (N-hydroxybenzamide) in which the hydroxamic acid group has been converted to the corresponding 2,3-dihydroxypropyl ester and in which the benzene ring has been substituted at position by a (2-fluoro-4-iodophenyl)amino group and at positions 3 and 4 by fluorines (the R enantiomer).

Biochem/physiol Actions

PD 0325901 is a potent MKK1 (MEK1) and MKK2 (MEK2) inhibitor. The Ki is 1.1 and 0.79 nM for MEK1 and MEK2, respectively. PD 0325901 was inactive against a panel of 27 other kinases. PD 0325901 inhibited C26 tumor pERK by 75% when dosed at 25 mg/kg in mice.

storage

-20°C

Background

PD 0325901 is a potent and selective non-ATP competitive MEK inhibitor. This small molecule is highly effective at inhibiting cell growth and proliferation in various cancer cells. The potency of PD 0325901 has been illustrated by the inhibition of ERK phosphorylation in mouse and human cell models with an IC50 of 0.33 nM and between 20-50 nM, respectively. PD 0325901 increases the self-renewal of mouse embryonic stem cells by enhancing the expression of pluripotency genes and acts as an antagonist for retinoic acid induced cell differentiation.

References

[1] The biological profile of PD0325901: A second generation analog of CI-1040 with improved pharmaceutical potential
[2] LUDOVICA CIUFFREDA . Growth-Inhibitory and Antiangiogenic Activity of the MEK Inhibitor PD0325901 in Malignant Melanoma with or without BRAF Mutations[J]. Neoplasia, 2009, 11 8: Pages 720-731, W1-W6. DOI:10.1593/neo.09398
[3] ZHIYING AI. Maintenance of Self-Renewal and Pluripotency in J1 Mouse Embryonic Stem Cells through Regulating Transcription Factor and MicroRNA Expression Induced by PD0325901[J]. Stem Cells International, 2015, 2016 1. DOI:10.1155/2016/1792573
[4] CUIPING LI. MEK inhibitor PD0325901 and vitamin C synergistically induce hypomethylation of mouse embryonic stem cells.[J]. Oncotarget, 2016: 39730-39739. DOI:10.18632/oncotarget.9452
[5] WENLIN LI. Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors.[J]. Cell stem cell, 2009, 4 1: 16-19. DOI:10.1016/j.stem.2008.11.014

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