1448189-80-7

Basic information

• Product Name: (2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride
• Synonyms: (2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride;Protein degrader 1 (hydrochloride);ULM-1;MDK7526 HCl;(2S,4R)-1-((S)-2-Amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine;ULM-1(MDK7526HCL);VHL Ligand 1 (hydrochloride)
• CAS NO: 1448189-80-7
• Molecular Formula: C₂₂H₃₀N₄O₃S*ClH
• Molecular Weight: 467.02454
• EINECS: 604-604-1
• Mol File: 1448189-80-7.mol
• Article Data: 19

Chemical Properties

• Appearance: /
• Storage Temp.: 2-8°C
• CAS DataBase Reference: (2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: (2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride(1448189-80-7)
• EPA Substance Registry System: (2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride(1448189-80-7)

Safety Data

• Hazardous Substances Data: 1448189-80-7(Hazardous Substances Data)

Usage

Description

VHL ligand 1 is a building block in the synthesis of proteolysis-targeting chimera technologies (PROTACs). It is the von Hippel-Lindau (VHL) E3 ligase binding portion of some VHL-based PROTACs, including BET PROTAC MZ1 (Item No. 21622).

Uses

Different sources of media describe the Uses of 1448189-80-7 differently. You can refer to the following data:
1. (2S,4R)-1-((S)-2-Amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide Hydrochloride acts as a reagent in the synthesis of PROTAC compounds that mediated the degration of oncogenic c-ABL and BCR-ABL.
2. (S,R,S)-AHPC (HCl salt) is a ligand used in the recruitment of the von Hippel-Lindau (VHL) protein for targeted protein degradation and PROTAC (proteolysis-targeting chimeras) technology. This (S,R,S) conformation is the active variant, and (S,S,S) is the inactive derivative (cat#901487) used as a negative control.

Upstream product

• 13726-69-7 (2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid 
• 3959-07-7 4-Bromobenzylamine 
• 1448189-89-6 tert-butyl (2S,4R)-2-[(4-bromophenyl)methylcarbamoyl]-4-hydroxypyrrolidine-1-carboxylate 
• 1448191-54-5 tert‐butyl (2S,4R)‐4‐hydroxy‐2‐({[4‐(4‐methyl‐1,3‐thiazol‐5‐yl)phenyl]methyl}carbamoyl)pyrrolidine‐1‐carboxylate 
• 1448189-45-4 (2S,4R)-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide 
• 2044838-29-9 1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methanamine hydrochloride 
• 68819-84-1 tert-butyl N-(4-bromobenzyl)carbamate 
• 122957-57-7 4-(4-methyl-1,3-thiazol-5-yl)benzonitrile 
• 623-00-7 4-bromobenzenecarbonitrile 
• 1448189-30-7 1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methaneamine 
• 1448189-29-4 2-(trimethylsilyl)ethyl 4-(4-methylthiazol-5-yl)benzylcarbamate 
• 1448189-28-3 2-(trimethylsilyl)ethyl 4-bromobenzylcarbamate 
• 1448189-98-7 tert‐butyl N‐[(2S)‐1‐[(2S,4R)‐4‐hydroxy‐2‐({[4‐(4‐methyl‐1,3‐thiazol‐5‐yl)phenyl]methyl}carbamoyl)pyrrolidin‐1‐yl]‐3,3‐dimethyl‐1‐oxobutan‐2‐yl]carbamate 
• 1448189-90-9 (2S,4R)-4-hydroxy-N-{ [4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide hydrochloride 

Downstream Products

• 1618678-49-1 (2S,4R)-1-((S)-2-(tert-butyl)-18-((7R,8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-7-yl)-4-oxo-6,9,12-trioxa-3-azaoctadecan-1-oyl)-4-hydroxy-N-( 4-( 4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide 
• 1618678-50-4 (2S,4R)-1-((S)-2-(2-(2-(2-(4-(4-((7R,8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-7-yl)butyl)-2-oxopiperazin-1-yl)ethoxy)ethoxy)acetamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide 
• 1618678-51-5 (2S,4R)-1-((S)-2-(2-(4-((7R,8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-7-yl)butoxy)acetamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide 
• 1448189-27-2 (2S,4R)-1-((S)-2-(tert-butyl)-21-((7R,8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-7-yl)-16-methyl-4-oxo-7,10,13-trioxa-3,16-diazahenicosan-1-oyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide 
• 1618678-45-7 (2S,4R)-1-((S)-2-(tert-butyl)-14-(4-(5-((7R,8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-7-yl)pentyl)piperazin-1-yl)-4-oxo-6,9,12-trioxa-3-azatetradecan-1-oyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide 
• 1618678-46-8 (2S,4R)-1-((S)-2-(tert-butyl)-20-((7R,8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-7-yl)-15-methyl-4-oxo-6,9,12-trioxa-3,15-diazaicosan-1-oyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide 
• 1448189-04-5 (2S,4R)-1-((S)-2-(tert-butyl)-19-((7R,8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-7-yl)-4-oxo-6,9,12,15-tetraoxa-3-azanonadecan-1-oyl)-4-hydroxy-N-( 4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide 
• 1448189-17-0 (2S,4R)-1-((S)-22-((7R,8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-7-yl)-2-isopropyl-4-oxo-6,9,12,15,18-pentaoxa-3-azadocosan-1-oyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide 
• 2064292-52-8 (2S,4R)-1-[(2S)-2-(14-amino-3,6,9,12-tetraoxatetradecanamido)-3,3-dimethylbutanoyl]-4-hydroxy-N-[ [4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide 

Relevant articles and documents

BIFUNCTIONAL COMPOUNDS

The invention provides a bifunctional compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein said Targeting Ligand, Linker and Degron are as described herein.

TAU-PROTEIN TARGETING COMPOUNDS AND ASSOCIATED METHODS OF USE

The present disclosure relates to bifunctional compounds, which find utility as modulators of tan protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tan protein, such that tan protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tan. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tan protein. Diseases or disorders that result from aggregation or accumulation of tan protein are treated or prevented with compounds and compositions of the present disclosure.

COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE 1 PROTEINS

The present invention relates to compounds comprising an interleukin-1 receptor-associated kinase 1 (IRAK1) protein binding moiety and a Von Hippel-Lindau (VHL) E3 ubiquitin ligase binding moiety, and associated methods of use. The compounds are useful as modulators of targeted ubiquitination, especially with respect to IRAK1, which is degraded by the compounds according to the invention.