531088 VCP Inhibitor III, NMS-873 - CAS 1418013-75-8 - Calbiochem

531088
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      Overview

      Replacement Information

      Key Specifications Table

      Empirical FormulaCAS #
      C₂₇H₂₈N₄O₃S₂ 1418013-75-8

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          Glass bottle 10 mg
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          Description
          OverviewA cell-permeable triazolylpyridine compound that potently inhibits VCP ATPase activity in a non-ATP-competitive manner (IC50/[ATP] = 20 nM/1 mM & 30 nM/60 µM; [wt hVCP] = 10 nM) via an allosteric mechanism where the inhibitor targets the lateral tunnel formed by the D1 & D2 domains of one VCP protomer together with the D1 from the adjacent VCP molecule in the hexamer, effectively locking the protomer in a rigid conformation and thereby preventing the release of bound ADP for successful propagation of interprotomer ATP hydrolysis cycle, while being ineffective against a panel of 53 kinases or the ATPase activities of 4 other AAA (ATPase Associated with diverse/various cellular Activities) ATPases (NSF, SPATAS, VPS4B, and cdc6) and Hsp90 (by <15% at 10 µM). In agreement with siRNA-mediated VCP knockdown, NMS-873 is shown to prevent VCP from extracting ubiquitinated client proteins, including cyclin E & Mcl-1, for proteasomal degradation, resulting in cellular UPR (unfold protein response) activation, autophagy induction, and eventual apoptosis in HCT-116 cultures in a dose- and time-dependent manner (0.5 to 5 µM; 8 to 72 h). Anti-cancer studies using a panel of 40 various hematological and solid tumor lines reveal wide-spread sensitivities to NMS-873-induced killings (IC50 from 80 nM to 2 µM), differing in degrees than those observed with the proteasome inhibitor Bortezomib (Cat. No. Cat. No. 504314). Exhibits high clearance and low bioavailability in in vivo studies.

          Please note that the molecular weight for this compound is batch-specific due to variable water content.
          Catalogue Number531088
          Brand Family Calbiochem®
          SynonymsERAD Inhibitor III, NMS873, 3-(3-(Cyclopentylthio)-5-((2-methyl-4ʹ-(methylsulfonyl)biphenyl-4-yloxy)methyl)-4H-1,2,4-triazol-4-yl)pyridine, 3-(3-Cyclopentylsulfanyl-5-(4ʹ-methanesulfonyl-2-methyl-biphenyl-4-yloxymethyl)-[1,2,4]triazol-4-yl)-pyridine, Valosin-containing Protein Inhibitor III, p97 Inhibitor III
          References
          ReferencesMagnaghi, P., et al. 2013. Nat. Chem. Biol. 9, 548.
          Polucci, P., et al. 2013. J. Med. Chem. 56, 437.
          Product Information
          CAS number1418013-75-8
          FormLight beige powder
          Hill FormulaC₂₇H₂₈N₄O₃S₂
          Chemical formulaC₂₇H₂₈N₄O₃S₂
          ReversibleY
          Applications
          Biological Information
          Primary TargetVCP
          Purity≥98% by HPLC
          Physicochemical Information
          Cell permeableY
          Dimensions
          Materials Information
          Toxicological Information
          Safety Information according to GHS
          Safety Information
          Product Usage Statements
          Storage and Shipping Information
          Ship Code Ambient Temperature Only
          Toxicity Standard Handling
          Storage +2°C to +8°C
          Protect from Light Protect from light
          Do not freeze Ok to freeze
          Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
          Packaging Information
          Packaged under inert gas Packaged under inert gas
          Transport Information
          Supplemental Information
          Specifications

          Documentation

          VCP Inhibitor III, NMS-873 - CAS 1418013-75-8 - Calbiochem SDS

          Title

          Safety Data Sheet (SDS) 

          References

          Reference overview
          Magnaghi, P., et al. 2013. Nat. Chem. Biol. 9, 548.
          Polucci, P., et al. 2013. J. Med. Chem. 56, 437.
          Data Sheet

          Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.

          Revision31-July-2014 JSW
          SynonymsERAD Inhibitor III, NMS873, 3-(3-(Cyclopentylthio)-5-((2-methyl-4ʹ-(methylsulfonyl)biphenyl-4-yloxy)methyl)-4H-1,2,4-triazol-4-yl)pyridine, 3-(3-Cyclopentylsulfanyl-5-(4ʹ-methanesulfonyl-2-methyl-biphenyl-4-yloxymethyl)-[1,2,4]triazol-4-yl)-pyridine, Valosin-containing Protein Inhibitor III, p97 Inhibitor III
          DescriptionA cell-permeable triazolylpyridine compound that potently inhibits VCP ATPase activity in a non-ATP-competitive manner (IC50/[ATP] = 20 nM/1 mM & 30 nM/60 µM; [wt hVCP] = 10 nM) via an allosteric mechanism where the inhibitor targets the lateral tunnel formed by the D1 & D2 domains of one VCP protomer together with the D1 from the adjacent VCP molecule in the hexamer, effectively locking the protomer in a rigid conformation and thereby preventing the release of bound ADP for successful propagation of interprotomer ATP hydrolysis cycle, while being ineffective against a panel of 53 kinases or the ATPase activities of 4 other AAA (ATPase Associated with diverse/various cellular Activities) ATPases (NSF, SPATAS, VPS4B, and cdc6) and Hsp90 (by <15% at 10 µM). In agreement with siRNA-mediated VCP knockdown, NMS-873 is shown to prevent VCP from extracting ubiquitinated client proteins, including cyclin E & Mcl-1, for proteasomal degradation, resulting in cellular UPR (unfold protein response) activation, autophagy induction, and eventual apoptosis in HCT-116 cultures in a dose- and time-dependent manner (0.5 to 5 µM; 8 to 72 h). Anti-cancer studies using a panel of 40 various hematological and solid tumor lines reveal wide-spread sensitivities to NMS-873-induced killings (IC50 from 80 nM to 2 µM), differing in degrees than those observed with the proteasome inhibitor Bortezomib (Cat. No. Cat. No. 504314). Exhibits high clearance and low bioavailability in in vivo studies.
          FormLight beige powder
          Intert gas (Yes/No) Packaged under inert gas
          CAS number1418013-75-8
          Chemical formulaC₂₇H₂₈N₄O₃S₂
          Purity≥98% by HPLC
          Storage +2°C to +8°C
          Protect from light
          Do Not Freeze Ok to freeze
          Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
          Toxicity Standard Handling
          ReferencesMagnaghi, P., et al. 2013. Nat. Chem. Biol. 9, 548.
          Polucci, P., et al. 2013. J. Med. Chem. 56, 437.