912999-49-6

Basic information

• Product Name: (2,4-dihydroxy-5-isopropylphenyl)(5-((4-Methylpiperazin-1-yl)Methyl)isoindolin-2-yl)Methanone
• Synonyms: (2,4-dihydroxy-5-isopropylphenyl)(5-((4-Methylpiperazin-1-yl)Methyl)isoindolin-2-yl)Methanone;4-({5-[(4-Methylpiperazin-1-yl)Methyl]-2,3-dihydro-1H-isoindol-2-yl}carbonyl)-6-(propan-2-yl)benzene-1,3-diol;[1,3-Dihydro-5-[(4-methyl-1-piperazinyl)methyl]-2H-isoindol-2-yl][2,4-dihydroxy-5-(1-methylethyl)phenyl]methanone;Onalespib;Onalespib (AT13387);[1,3-Dihydro-5-[(4-methyl-1-piperazinyl)methyl]-2H-isoindol-2-yl][2,4-dihydroxy-5-(1-methylethyl)phenyl]methanone AT13387;AT13387, >=98%;Onalespib Lactate
• CAS NO: 912999-49-6
• Molecular Formula: C₂₄H₃₁N₃O₃
• Molecular Weight: 409.52124
• Product Categories: Inhibitor;Inhibitors
• Mol File: 912999-49-6.mol
• Article Data: 10

Chemical Properties

• Boiling Point: 605.7±55.0 °C(Predicted)
• Appearance: /
• Density: 1.237
• Solubility: insoluble in H2O; ≥13.25 mg/mL in DMSO; ≥47.7 mg/mL in EtOH with ultrasonic
• PKA: 8.50±0.48(Predicted)
• CAS DataBase Reference: (2,4-dihydroxy-5-isopropylphenyl)(5-((4-Methylpiperazin-1-yl)Methyl)isoindolin-2-yl)Methanone(CAS DataBase Reference)
• NIST Chemistry Reference: (2,4-dihydroxy-5-isopropylphenyl)(5-((4-Methylpiperazin-1-yl)Methyl)isoindolin-2-yl)Methanone(912999-49-6)
• EPA Substance Registry System: (2,4-dihydroxy-5-isopropylphenyl)(5-((4-Methylpiperazin-1-yl)Methyl)isoindolin-2-yl)Methanone(912999-49-6)

Safety Data

• Hazardous Substances Data: 912999-49-6(Hazardous Substances Data)

Usage

Description

Onalespib is a selective inhibitor of Hsp90 (IC50 = 18 nM). It induces the degradation of specific Hsp90 client proteins, including mutant EGFR, for up to seven days in tumor cell lines in vitro and up to three days in vivo. Onalespib is retained in tumor xenografts and is efficacious in a range of xenograft models.

Upstream product

• 912999-93-0 5-(4-methyl-piperazin-1-ylmethyl)-2,3-dihydro-1H-isoindole 
• 912545-09-6 2,4-bis(benzyloxy)-5-(prop-1-en-2-yl)benzoic acid 
• 912545-15-4 benzyl 2,4-bis(benzyloxy)-5-(prop-1-en-2-yl)benzoate 
• 89-86-1 4-hydroxysalicylic acid 
• 121903-70-6 benzyl 2,4-bis(benzyloxy)benzoate 
• 912545-14-3 benzyl 2,4-bis(benzyloxy)-5-bromobenzoate 
• 1415742-78-7 7-hydroxy-6-iso-propyl-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one 
• 109-01-3 1-methyl-piperazine 
• 1015484-22-6 1-methyl-4-((trifluoro-λ⁴-boranyl)methyl)piperazine potassium 
• 201940-08-1 5-bromo-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester 
• 6941-75-9 5-Bromoisoindoline-1,3-dione 
• 127168-84-7 5-bromoisoindoline 
• 913000-35-8 (2,4-bis-benzyloxy-5-isopropyl-phenyl)-[5-(4-methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindol-2-yl]-methanone 
• 1019890-25-5 (2,4-dihydroxy-5-(2-hydroxyprop-2-yl)-phenyl)-[5-(4-methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindol-2-yl]-methanone 

Downstream Products

• 1019889-35-0 (2,4-dihydroxy-5-isopropyl-phenyl)-[5-(4-methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindol-2-yl]-methanone L-lactate salt 
• 1191108-43-6 carbonic acid 5-tert-butoxycarbonyloxy-4-isopropyl-2-[5-(4-methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindole-2-carbonyl]-phenyl ester tert-butyl ester 
• 1191108-29-8 diethyl-carbamic acid 5-diethylcarbamoyloxy-2-isopropyl-4-[5-(4-methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindole-2-carbonyl]-phenyl ester 

Relevant articles and documents

The succinct synthesis of AT13387, a clinically relevant Hsp90 inhibitor

AT13387 is an orally bioavailable clinical candidate developed to inhibit heat shock protein 90 (Hsp90). This article describes a modified synthetic route for the multi-gram production of AT13387 in 46% overall yield. The modified synthetic route is short

Total synthesis of resorcinol amide Hsp90 inhibitor AT13387

The synthesis of C-5-substituted resorcinol amide AT13387, a known Hsp90 inhibitor currently in clinical trials, is reported without the use of phenolic protection in an overall yield of 13.4%. Biomimetic aromatization and Suzuki-Miyaura cross coupling ap

Discovery of (2,4-Dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1- ylmethyl)-1,3-dihydroisoindol-2-yl]methanone (AT13387), a novel inhibitor of the molecular chaperone Hsp90 by fragment based drug design

Inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) are currently generating significant interest in clinical development as potential treatments for cancer. In a preceding publication (DOI: 10.1021/jm100059d) we describe Astex's approach to screening fragments against Hsp90 and the subsequent optimization of two hits into leads with inhibitory activities in the low nanomolar range. This paper describes the structure guided optimization of the 2,4-dihydroxybenzamide lead molecule 1 and details some of the drug discovery strategies employed in the identification of AT13387 (35), which has progressed through preclinical development and is currently being tested in man.