958025-66-6

Basic information

• Product Name: MPC3100
• Synonyms: MPC3100;(2S)-1-[4-[2-[6-Amino-8-[(6-bromo-1,3-benzodioxol-5-yl)thio]-9H-purin-9-yl]ethyl]-1-piperidinyl]-2-hydroxy-1-propanone
• CAS NO: 958025-66-6
• Molecular Formula: C₂₂H₂₅BrN₆O₄S
• Molecular Weight: 549.4407
• EINECS: 200-258-5
• Mol File: 958025-66-6.mol
• Article Data: 3

Chemical Properties

• Appearance: /
• Solubility: Soluble in DMSO
• CAS DataBase Reference: MPC3100(CAS DataBase Reference)
• NIST Chemistry Reference: MPC3100(958025-66-6)
• EPA Substance Registry System: MPC3100(958025-66-6)

Safety Data

• Hazardous Substances Data: 958025-66-6(Hazardous Substances Data)

Usage

Uses

MPC-3100 is a recently discovered fully synthetic purine-based Hsp90 Inhibitor exhibiting anticancer properties

Biological Activity

mpc-3100 is a purine-based inhibitor of hsp90 with ic50 value of 60nm [1].mpc-3100 targets the n-terminal atp-binding site of hsp90 and blocks the activity of atpase. in the her2-luciferase degradation assay, mpc-3100 reduces this client protein of hsp90 with ic50 value of 60nm. in hct-116 cell lines, mpc-3100 inhibits cell proliferation with ic50 value of 540nm. besides that, mpc-3100 shows a broad spectrum anti-proliferative activity against various cancer cell lines, such as nci-n87 and du-145. mpc-3100 also inhibits tumor growth in the nci-n87 gastric cancer xenograft mode. moreover, pk studies show that mpc-3100 displays a superior oral pk profile, good overall exposure and a reasonable hepatic clearance rate. phase i clinical studies demonstrate mpc-3100 is safe and tolerated when administered at doses below 600 mg per day [1].

references

[1] kim sh, bajji a, tangallapally r, markovitz b, trovato r, shenderovich m, baichwal v, bartel p, cimbora d, mckinnon r, robinson r, papac d, wettstein d, carlson r, yager km. discovery of (2s)-1-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9h-purin-9-yl}ethyl)piperidin-1-yl]-2-hydroxypropan-1-one (mpc-3100), a purine-based hsp90 inhibitor. j med chem. 2012 sep 13;55(17):7480-501.

Upstream product

• 1156468-55-1 tert-butyl 4-[2-(6-amino-9H-purin-9-yl)ethyl]piperidine-1-carboxylate 
• 36394-75-9 (S)-2-acetoxypropanoyl chloride 
• 169457-73-2 tert-butyl 4-(2-bromoethyl)piperidine-1-carboxylate 
• 66224-66-6 adenine 
• 147699-19-2 tert-butyl 4-{2-[(methylsulfonyl)oxy]ethyl}piperidine-1-carboxylate 
• 1396789-93-7 C₁₈H₂₆O₄S 
• 1289181-45-8 2-ethylhexyl 3-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-propanoate 
• 2635-13-4 1,2-(methylenedioxy)-4-bromobenzene 
• 1156468-58-4 tert-butyl 4-[2-(6-amino-8-bromo-9H-purin-9-yl)ethyl]piperidine-1-carboxylate 
• 89151-44-0 4-(2-hydroxyethyl)piperidine-1-carboxylic acid tert-butyl ester 
• 622-26-4 4-(2-Hydroxyethyl)piperidine 
• 5279-32-3 5,6-dibromo-1,3-benzodioxole 
• 7390-62-7 8-mercaptoadenine 
• 852030-25-2 8-(7-bromo-2,3-dihydro-benzo[1,4]dioxin-6-ylsulfanyl)adenine 

Downstream Products

• 1404475-90-6 C₃₃H₃₈BrN₆O₉PS 
• 1404473-96-6 (2S)-1-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-oxopropan-2-yl 3-(phosphonooxy)benzoate 
• 1404473-71-7 (2S)-1-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-oxopropan-2-yl hydrogen sulfate sodium salt 

Relevant articles and documents

Discovery of an l-alanine ester prodrug of the Hsp90 inhibitor, MPC-3100

Various types of Hsp90 inhibitors have been and continue to undergo clinical investigation. One development candidate is the purine-based, synthetic Hsp90 inhibitor 1 (MPC-3100), which successfully completed a phase I clinical study. However, further clin

Discovery of (2 S)-1-[4-(2-{6-amino-8-[(6-bromo-1,3-benzodioxol-5-yl) sulfanyl]-9 H-purin-9-yl}ethyl)piperidin-1-yl]-2-hydroxypropan-1-one (MPC-3100), a purine-based Hsp90 inhibitor

Modulation of Hsp90 (heat shock protein 90) function has been recognized as an attractive approach for cancer treatment, since many cancer cells depend on Hsp90 to maintain cellular homeostasis. This has spurred the search for small-molecule Hsp90 inhibitors. Here we describe our lead optimization studies centered on the purine-based Hsp90 inhibitor 28a containing a piperidine moiety at the purine N9 position. In this study, key SAR was established for the piperidine N-substituent and for the congeners of the 1,3-benzodioxole at C8. These efforts led to the identification of orally bioavailable 28g that exhibits good in vitro profiles and a characteristic molecular biomarker signature of Hsp90 inhibition both in vitro and in vivo. Favorable pharmacokinetic properties along with significant antitumor effects in multiple human cancer xenograft models led to the selection of 28g (MPC-3100) as a clinical candidate.