1616077-51-0

Basic information

• Product Name: 1616077-51-0
• Synonyms: (2S)-1-Amino-3-(1,2,3,4-tetrahydroisoquinolin-2-yl)propan-2-ol
• CAS NO: 1616077-51-0
• Molecular Formula: C₁₂H₁₈N₂O
• Molecular Weight: 206.28412
• Mol File: 1616077-51-0.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 364.2±32.0 °C(Predicted)
• Appearance: /
• Density: 1.127±0.06 g/cm3(Predicted)
• PKA: 12.35±0.35(Predicted)
• CAS DataBase Reference: 1616077-51-0(CAS DataBase Reference)
• NIST Chemistry Reference: 1616077-51-0(1616077-51-0)
• EPA Substance Registry System: 1616077-51-0(1616077-51-0)

Safety Data

• Hazardous Substances Data: 1616077-51-0(Hazardous Substances Data)

Usage

Family

Amino acid

Usage

Synthesis of pharmaceutical products and other organic molecules

Chemical structure

Six-carbon chain with a methyl group and an amino group attached to a central carbon atom

Potential applications

Development of new drugs and biologically active molecules

Ongoing research

Evaluation of potential uses and properties

Upstream product

• 1616064-77-7 (R)-2-(oxiran-2-ylmethyl)-1,2,3,4-tetrahydroisoquinoline 
• 91-21-4 1,2,3,4-tetrahydroisoquinoline 

Downstream Products

• 1616392-22-3 GSK-3326595 
• 1616391-87-7 GSK591 
• 1616246-32-2 (S)-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-3-((tetrahydro-2H-pyran-4-yl)amino)benzamide 
• 1616246-07-1 (S)-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-3-(pyridin-2-yl)benzamide 

Relevant articles and documents

Discovery of First-in-Class Protein Arginine Methyltransferase 5 (PRMT5) Degraders

The aberrant expression of protein arginine methyltransferase 5 (PRMT5) has been associated with multiple cancers. Using the proteolysis targeting chimera technology, we discovered a first-in-class PRMT5 degrader 15 (MS4322). Here, we report the design, synthesis, and characterization of compound 15 and two structurally similar controls 17 (MS4370) and 21 (MS4369), with impaired binding to the von Hippel-Lindau E3 ligase and PRMT5, respectively. Compound 15, but not 17 and 21, effectively reduced the PRMT5 protein level in MCF-7 cells. Our mechanism studies indicate that compound 15 degraded PRMT5 in an E3 ligase-and proteasome-dependent manner. Compound 15 also effectively reduced the PRMT5 protein level and inhibited growth in multiple cancer cell lines. Moreover, compound 15 was highly selective for PRMT5 in a global proteomic study and exhibited good plasma exposure in mice. Collectively, compound 15 and its two controls 17 and 21 are valuable chemical tools for exploring the PRMT5 functions in health and disease.

PRMT5 INHIBITORS AND USES THEREOF

Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.

Structure and Property Guided Design in the Identification of PRMT5 Tool Compound EPZ015666

The recent publication of a potent and selective inhibitor of protein methyltransferase 5 (PRMT5) provides the scientific community with in vivo-active tool compound EPZ015666 (GSK3235025) to probe the underlying pharmacology of this key enzyme. Herein, we report the design and optimization strategies employed on an initial hit compound with poor in vitro clearance to yield in vivo tool compound EPZ015666 and an additional potent in vitro tool molecule EPZ015866 (GSK3203591).