866405-64-3

Basic information

• Product Name: 6-[4-(2-PIPERIDIN-1-YLETHOXY)PHENYL]-3-PYRIDIN-4-YLPYRAZOLO[1,5-A]PYRIMIDINE
• Synonyms: AMPK INHIBITOR;6-[4-(2-PIPERIDIN-1-YLETHOXY)PHENYL]-3-PYRIDIN-4-YLPYRAZOLO[1,5-A]PYRIMIDINE;COMPOUND C;AMPK Inhibitor, Compound C, Dorsomorphin;BML-275;Dorsomorphin;6-[4-[2-(1-Piperidinyl)ethoxy]phenyl]-3-(4-pyridinyl)-pyrazolo[1,5-a]pyrimidinedihydrochloride;Dorsomorphin dihydrochloride
• CAS NO: 866405-64-3
• Molecular Formula: C24H25N5O
• Molecular Weight: 399.4882
• Product Categories: Inhibitors
• Mol File: 866405-64-3.mol
• Article Data: 1

Chemical Properties

• Appearance: white to beige/
• Density: 1.255 g/cm³
• Refractive Index: 1.67
• Storage Temp.: 2-8°C
• Solubility: DMSO: >2mg/mL (warmed)
• PKA: 8.53±0.10(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: 6-[4-(2-PIPERIDIN-1-YLETHOXY)PHENYL]-3-PYRIDIN-4-YLPYRAZOLO[1,5-A]PYRIMIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: 6-[4-(2-PIPERIDIN-1-YLETHOXY)PHENYL]-3-PYRIDIN-4-YLPYRAZOLO[1,5-A]PYRIMIDINE(866405-64-3)
• EPA Substance Registry System: 6-[4-(2-PIPERIDIN-1-YLETHOXY)PHENYL]-3-PYRIDIN-4-YLPYRAZOLO[1,5-A]PYRIMIDINE(866405-64-3)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22
• Safety Statements: 36/37
• WGK Germany: 3
• Hazardous Substances Data: 866405-64-3(Hazardous Substances Data)

Usage

Description

Dorsomorphin (866405-64-3) is a potent, selective and ATP-competitive inhibitor of AMP-activated protein kinase (AMPK) (Ki = 109 nM).1 It displays no significant inhibition of ZAPK, SYK, PKCT, PKA and JAK3. It inhibits bone morphogenetic protein (BMP) type I receptors (ALK2, ALK3 and ALK6).2 Dorsomorphin has been shown to promote cardiomyogenesis in mouse embryonic stem cells (ESCs) in vitro.3 Dorsomorphin also induces autophagy in cancer cell lines via a mechanism independent of AMPK inhibition.4

Uses

Different sources of media describe the Uses of 866405-64-3 differently. You can refer to the following data:
1. Dorsomorphin has been used:as an inhibitor of adenosine monophosphate-activated protein kinase (AMPK) to find the effects of trans-resveratrol on lipid mobilization in 3T3-L1 (a murine cell line of adipocytes) cellsas an AMPK inhibitor, to indicate the involvement of AMPK/mTOR (mammalian target of rapamycin) pathway in LRG (liraglutide) -induced autophagyin the induction step, employed in in vitro differentiation of Friedreich′s ataxia (FRDA) and induced pluripotent stem cells (iPSCs) to neurospheres and neurons using ES (embryonic stem cell) media
2. A potent inhibitor of AMPK and fatty acid biosynthesis.

Definition

ChEBI: A pyrazolopyrimidine that is pyrazolo[1,5-a]pyrimidine which is substituted at positions 3 and 6 by pyridin-4-yl and p-[2-(piperidin-1-yl)ethoxy]phenyl groups, respectively. It is a potent, selective, reversible, and ATP-competiti e inhibitor of AMPK (AMP-activated protein kinase, EC 2.7.11.31) and a selective inhibitor of bone morphogenetic protein (BMP) signaling.

General Description

A cell-permeable pyrrazolopyrimidine compound that inhibits against KDR/VEGFR2, ALK2/BMPR-I, AMPK kinase activity (IC50 = 25.1, 148, and 234.6 nM, respectively), while exhibiting much reduced or little effect toward ALK5/TGFβR-I, ZAPK, Syk, PKCθ, PKA, or JAK3. Shown to block both BMP pathway-dependent dorsoventral development (EC100 = 2.5 μM) and VEGF signaling-dependent intersomitic vessel formation (EC50 = 5 μM) in zebrafish embryo in vivo. Commonly used in combination with AMPK activators AICAR (Cat. No. 123040) and/or Metformin (Cat. No. 317240) for studying AMPK-dependent cellular events in vitro and physiological responses in animals in vivo.

Biological Activity

Potent and selective inhibitor of AMP-activated protein kinase (AMPK) (K i = 109 nM). Displays no significant activity on several structurally related kinases including ZAPK, SYK, PKC θ , PKA and JAK3. Inhibits AMPK activation induced by AICAR and metformin. Also inhibits bone morphogenic protein (BMP) type I receptors (ALK2, ALK3 and ALK6). Promotes cardiomyogenesis in mouse embryonic stem cells (ESCs) in vitro .

Biochem/physiol Actions

Target IC50: 25.1, 148, and 234.6 nM, against KDR/VEGFR2, ALK2/BMPR-I, AMPK kinase activity, respectively

References

1) Zhou et al. (2001) Role of AMP-activated protein kinase in mechanism of metformin action; J. Clin. Invest. 108 1167 2) Yu et al. (2008) Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism; Nat. Chem. Biol. 4 33 3) Hao et al. (2008) Dorsomorphin, a selective small molecule inhibitor of BMP signaling, promotes cardiomyogenesis in embryonic stem cells; PLoS ONE, 3 2904 4) Vucicevic et al. (2011) Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway; Autophagy 7 40

InChI:InChI=1/C24H25N5O/c1-2-12-28(13-3-1)14-15-30-22-6-4-19(5-7-22)21-16-26-24-23(17-27-29(24)18-21)20-8-10-25-11-9-20/h4-11,16-18H,1-3,12-15H2

Upstream product

• 2008-75-5 N-chloroethylpiperidine hydrochloride 
• 515880-87-2 6-(4-hydroxyphenyl)-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidine 
• 216661-58-4 3-(pyridin-4-yl)-6-(4-methoxyphenyl)-pyrazolo(1,5-A)pyrimidine 
• 65192-28-1 2-(4-methoxyphenyl)malondialdehyde 
• 100-09-4 4-methoxybenzoic acid 
• 216661-87-9 5-amino-4-(pyridin-4-yl)-1H-pyrazole 
• 103851-89-4 3-(dimethylamino)-2-(4-pyridyl)prop-2-enenitrile 
• 10445-91-7 4-(Chloromethyl)pyridine 
• 13121-99-8 pyridin-4-ylacetonitrile 

Relevant articles and documents

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