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391210-10-9 (PD0325901)

1

Identification

PD0325901 PD0325901
Name PD0325901
Formula C16H14F3IN2O4
MW 482.19
CAS No. 391210-10-9
EINECS
Smiles O=C(C1=CC=C(C(F)=C1NC2=CC=C(I)C=C2F)F)NOC[[email protected]](O)CO
Synonyms PD 0325901; PD325901; PD-0325901; (R)-N-(2,3-dihydroxypropoxy)-3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzamide
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
2

Introduction

PD0325901 (PD325901) is selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM. IC50 value: Target: MEK PD0325901 is a selective MEK1 and MEK2 inhibitor.

Background Information

Selective and non ATP-competitive MEK inhibitor ......by AOBIOUS INC

PD0325901 is a specific inhibitor of mitogen-activated protein kinase MEK. PD0325901 is a small molecular with the formula of C16H14F3IN2O4 and Molecular Weight of 482. MEK is a key component of the RAS/RAF/MEK/ERK signaling pathway that is frequently activated in human tumors, and MEK/ERK regulates cell proliferation, survival, and differentiation in response to extracellular signals. PD0325901 effectively reduces P-ERK levels and cell growth in vitro, and inhibits tumor growth in mouse model in vivo

References:
1. Noninvasive imaging of cell proliferation following mitogenic extracellular kinase inhibition by PD0325901. J Leyton, G Smith, M Lees, M Peruma. Molecular cancer Therapeutics. 2008
2. Targeting mitogen‐activated protein kinase kinase with the inhibitor PD0325901 decreases hepatocellular carcinoma growth in vitro and in mouse model. M Hennig, MT Yip‐Schneider, S Wentz, H Wu. Hepatology. 2010

......by Apexbio Technology LLC
PD-0325901 i a potent bioavailable and selective MEK inhibitor, which targets mitogen-activated protein kinase kinase (MAPK/ERK kinase or MEK) with potential antineoplastic activity. MEK inhibitor PD325901, a derivative of MEK inhibitor CI-1040, selective ......by BOC Sciences
PD0325901 is a selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM, roughly 500-fold more potent than CI-1040 on phosphorylation of ERK1 and ERK2. ......by MedChemexpress Co., Ltd.
PD-0325901 is a potent bioavailable and selective MEK inhibitor, which targets mitogen-activated protein kinase kinase (MAPK/ERK kinase or MEK) with potential antineoplastic activity. MEK inhibitor PD325901, a derivative of MEK inhibitor CI-1040, selectively binds to and inhibits MEK, which may result in the inhibition of the phosphorylation and activation of MAPK/ERK and the inhibition of tumor cell proliferation. The dual specific threonine/tyrosine kinase MEK is a key component of the RAS/RAF/MEK/ERK signaling pathway that is frequently activated in human tumors. ......by MedKoo Biosciences, Inc.
A selective, non ATP-competitive MEK inhibitor with IC50 of 0.33 nM; markedly inhibits ERK phosphorylation and growth of both BRAF mutant and wild-type melanoma cell lines with IC50 in the nanomolar range; significantly reduces the growth of papillary thyroid carcinoma cells in vitro and in vivo; orally active.Brain CancerPhase 2 Clinical ......by ProbeChem
PD0325901 is a selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM in cell-free assays, roughly 500-fold more potent than CI-1040 on phosphorylation of ERK1 and ERK2. Phase 2. ......by Selleck Chemicals LLC
PD0325901 (PD325901) is a selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM, roughly 500-fold more potent than CI-1040 on phosphorylation of ERK1 and ERK2. Phase 2. ......by Target Molecule Corp.
Potent MEK1 and MEK2 inhibitor. Inhibits MEK activity in mouse colon 26 cells (IC50 = 0.33 nM). Inhibits the growth of melanoma cell lines in vitro and in vivo; induces G1-phase cell cycle arrest and apoptosis in a mouse xenograft model. Also inhibits production of proangiogenic cytokines such as VEGF. Enhances generation of induced pluripotent stem cells (iPSCs). Orally active. ......by Tocris Bioscience Inc.
3

Protocol(Only for Reference)

Cell Experiment

Cell lines M14 (BRAFV600E) cells
Conditions 1 μM, 48 hours for cell cycle accumulation ≥100 nM, 72 hours for DNA decrease
Method PD0325901 caused a dose- and time-dependent cell cycle accumulation at the G1/S boundary and depletion of cells in the S-phase. It also caused a dose- and time-dependent increase in the percentage of cellswith sub-G1 DNA content, thus indicating induction of apoptosis. Compared with the kinetics and dose-response curve of cell cycle inhibition, DNA decrease to sub-G1 levels required longer times of exposure (72 hours) and higher concentrations of the drug (≥100 nM).
Source Apexbio Technology LLC
Cell lines PTC cells
Conditions 0.1 nM- 1 μM; 48 hours
Method PTC cells (1 × 104) are seeded in 24-well plates with 1 mL of medium for 4 days in a 37 °C incubator. MEK inhibitor PD0325901 at varying concentrations is added to the cells in triplicate on day 0. MTT dissolved in 0.8% NaCl solution at 5 mg/mL is added to each well (0.2 mL) on day 2 to test GI50 or every day for cell growth curves. The cells are incubated at 37 °C for 3 hours with MTT. The liquid is then aspirated from the wells and discarded. Stained cells are dissolved in 0.5 mL of DMSO and their absorption at 570 nm is measured using a Synergy HT multidetection microplate reader. For GI50, cell growth is calculated as 100 × (T − T0)/(C − T0), where T is the optical density of the wells treated with inhibitors after a 48-hour period, T0 is the optical density at time zero, and C is the control optical density with DMSO only.
Source Selleck Chemicals LLC

Animal Experiment

Animal Models Female CD-1 nude (nu/nu) mice injected with M14 (BRAFV600E) and ME8959 (wtBRAF) cells
Dosage Form Oral administration, 50 mg/kg per day for 21 days
Applications Daily oral treatment of established tumors with 50 mg/kg per day of PD0325901 significantly impaired in vivo tumor growth (60%-65% inhibition compared with controls at the end of a 21-day treatment cycle) in both M14 and ME8959 xenografts. The effects of PD0325901 were reversible, and tumors grew back after treatment interruption.
Source Apexbio Technology LLC
Animal Models Ncr-nu/nu mice bearing PTC cells
Dosage 20-25 mg/kg
Formulation 80 mM citric buffer (pH 7)
Administration Oral gavage
Source Selleck Chemicals LLC
4

Physical and Chemical Properties

Appearance:White to off-white solid EBNumber:EB000029104

Storage condition

Store at -20°C by Apexbio Technology LLC
Store at or below -20 oC. by LC Laboratoies
4°C by MedChemexpress Co., Ltd.

Solubility

Soluble in DMSO > 10 mM by Apexbio Technology LLC
DMSO: ≥ 20 mg/mL, H2O: < 1 mg/mL by CHEMSCENE, LLC
Soluble in DMSO at 12 mg/mL; soluble in ethanol at 6.3 mg/mL with slight warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 50-100 μM buffers, serum, or other additives may increase or decrease the aqueous so. by LC Laboratoies
DMSO: ≥ 20 mg/mL, H2O: < 1 mg/mL by MedChemexpress Co., Ltd.
(25°C) * In vitro DMSO 96 mg/mL (199.09 mM); Ethanol40 mg/mL (82.95 mM); Water<1 mg/mL (<1 mM); In vivo 30% PEG 400+5% Tween 80+ddH2O10mg/mL by Selleck Chemicals LLC
5

Mechanism and Indication

6

Clinical Information

Product Name Sponsor & Collaborators Indications Start Date End Date Phase
PD0325901 Pfizer Inc Non-small-cell lung cancer 2005/11/30 2007/3/23 Phase 2 Clinical
PD0325901 Pfizer Inc Stage IV melanoma 2004/2/29 2013/7/31 Phase 2 Clinical
PD0325901 Pfizer Inc Metastatic breast cancer 2004/2/29 2013/7/31 Phase 2 Clinical
PD0325901 Pfizer Inc Metastatic colon cancer 2004/2/29 2013/7/31 Phase 2 Clinical
PD0325901 Pfizer Inc Advanced solid tumor 2011/10/31 2014/11/30 Phase 1 Clinical
PD0325901 - Phase 2
7

Safety Data of PD0325901

Hazard Symbols : T,N
Risk Statements : 25-48-50
Safety Statements : 22-36/37/39-61
8

Spectral Information

9

Suppliers List

Company Price and Availability Country/Region
AOBIOUS INC 1mg/USD19() USA
AbMole BioScience USA
Adipogen Corporation USA
Apexbio Technology LLC USA
BOC Sciences 100mg/USD198(In stock)
Biochempartner Co., Ltd China
CHEMSCENE, LLC 5mg/USD60();10mg/USD108() USA
Cayman Chemical Company USA
Eastbang Pharmaceuticals Science &amp; Technology Co., Ltd CHINA
LC Laboratoies 5mg/USD44(In stock);10mg/USD67(In stock);25mg/USD122(In stock);50mg/USD188(In stock);100mg/USD292(In stock);200mg/USD479(In stock);500mg/USD972(In stock);1g/USD1440(In stock) USA
MedChemexpress Co., Ltd. 5mg/USD60();10mg/USD108() USA
MedKoo Biosciences, Inc. USA
ProbeChem
Selleck Chemicals LLC 5mg/USD70(In stock);10mg/USD120(In stock);10mM/1mLIn DMSO/USD140(In stock);25mg/USD270(In stock);100mg/USD770(In stock) USA
Shanghai Haoyuan Chemexpress Co., Ltd. 5mg/USD60();10mg/USD108() China
Target Molecule Corp. 5mg/USD78();10mg/USD102();25mg/USD144();50mg/USD198() USA
Tocris Bioscience Inc. USA
10

Related Products

Other Forms of 391210-10-9

Name CAS No Formula MW

Recommended Compounds in Autophagy MEK

Name CAS No Formula MW
Pirarubicin (Hydrochloride) 95343-20-7 C32H38ClNO12 664.1
Berberine (chloride) 633-65-8 C20H18ClNO4 371.8142
DMH-1 1206711-16-1 C24H20N4O 380.44
CB-839 1439399-58-2 C26H24F3N7O3S 571.57
H-89 (dihydrochloride) 130964-39-5 C20H22BrCl2N3O2S 519.2826
Shikonin 517-89-5 C16H16O5 288.3
H 89 127243-85-0 C20H20BrN3O2S 446.36
Eupatilin 22368-21-4 C18H16O7 344.32
Isoalantolactone 470-17-7 C15H20O2 232.32
Scutellarein 529-53-3 C15H10O6 286.24
Leonurine 24697-74-3 C14H21N3O5 311.33
Berbamine (dihydrochloride) 6078-17-7 C37H42Cl2N2O6 681.6452
Ruxolitinib (S enantiomer) 941685-37-6 C17H18N6 306.37
D-Glucosamine (Hydrochloride) 66-84-2 C6H14ClNO5 215.63
Schizandrin A 61281-38-7 C22H28O6 388.45
Schisandrol B 58546-54-6 C23H28O7 416.46
Schisandrol A 7432-28-2 C24H32O7 432.51
Icaritin 118525-40-9 C21H20O6 368.3799
Bicyclol 118159-48-1 C19H18O9 390.34
Azithromycin 83905-01-5 C38H72N2O12 748.9845

Recommended Compounds in Same Indication

Name CAS No Formula MW
OSI-930 728033-96-3 C22H16F3N3O2S 443.44
AT7867 857531-00-1 C20H20ClN3 337.85
Trametinib 871700-17-3 C26H23FIN5O4 615.39
NVP-BGJ398 872511-34-7 C26H31Cl2N7O3 560.48
BMS-599626 (Hydrochloride) 873837-23-1 C27H28ClFN8O3 567.01
RO4987655 874101-00-5 C20H19F3IN3O5 565.28
MGCD-265 analog 875337-44-3 C26H20FN5O2S2 517.5977
Crizotinib 877399-52-5 C21H22Cl2FN5O 450.34
Regorafenib (Hydrochloride) 835621-07-3 C21H16Cl2F4N4O3 519.28
Ostarine 841205-47-8 C19H14F3N3O3 389.33
AT9283 896466-04-9 C19H23N7O2 381.43
KX2-391 897016-82-9 C26H29N3O3 431.53
AT-101 90141-22-3 C30H30O8 518.55
MLN4924 905579-51-3 C21H25N5O4S 443.52
SNX-2112 908112-43-6 C23H27F3N4O3 464.48
IDO5L 914471-09-3 C9H7ClFN5O2 271.6356
ABC294640 915385-81-8 C23H25ClN2O 380.91
OTSSP167 1431697-89-0 C25H28Cl2N4O2 487.42
Dovitinib 405169-16-6 C21H21FN6O 392.43
SB-590885 405554-55-4 C27H27N5O2 453.54
11

Route of Synthesis

12

References

[1]. Barrett, Stephen D.; Bridges, Alexander J.; Dudley, David T.; The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901. Bioorganic & Medicinal Chemistry Letters (2008), 18(24), 6501-6504.

[2]. Barrett, Stephen D.; Bridges, Alexander J.; Dudley, David T.; The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901. Leyton, Julius; Smith, Graham; Lees, Mark; Perumal, Meg; Noninvasive imaging of cell proliferation following mitogenic extracellular kinase inhibition by PD0325901. Molecular Cancer Therapeutics (2008), 7(9), 3112-3121.

[3]. Torti VR, Wojciechowicz D, Hu W, John-Baptiste A, Evering W, Troche G, Marroquin LD, Smeal T, Yamazaki S, Palmer CL, Burns-Naas LA, Bagrodia S.Epithelial Tissue Hyperplasia Induced by the RAF Inhibitor PF-04880594 is Attenuated by a Clinically Well-Tolerated Dose of the MEK Inhibitor PD-0325901.Mol Cancer Ther. 2012 Jul 2.

[4]. Sheth PR, Liu Y, Hesson T, Zhao J, Vilenchik L, Liu YH, Mayhood TW, Le HV.Fully activated MEK1 exhibits compromised affinity for binding of allosteric inhibitors U0126 and PD0325901.Biochemistry. 2011 Sep 20;50(37):7964-76. Epub 2011 Aug 26.

[5]. Boasberg PD, Redfern CH, Daniels GA, Bodkin D, Garrett CR, Ricart AD.Pilot study of PD-0325901 in previously treated patients with advanced melanoma, breast cancer, and colon cancer.Cancer Chemother Pharmacol. 2011 Aug;68(2):547-52. Epub 2011 Apr 24.

Protocol Reference

[1] Ciuffreda L, Del Bufalo D, Desideri M, et al. Growth-inhibitory and antiangiogenic activity of the MEK inhibitor PD0325901 in malignant melanoma with or without BRAF mutations. Neoplasia, 2009, 11(8): 720-W6.

......by Apexbio Technology LLC
13

More Information

PD0325901

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