b-AP15

Catalog No.S4920 Synonyms: NSC687852

For research use only.

b-AP15 (NSC687852) is a deubiquitinases inhibitor for 19S proteasomes activity of Ub-AMC cleavage with IC50 of 2.1 μM.

b-AP15 Chemical Structure

CAS No. 1009817-63-3

Selleck's b-AP15 has been cited by 14 publications

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Biological Activity

Description b-AP15 (NSC687852) is a deubiquitinases inhibitor for 19S proteasomes activity of Ub-AMC cleavage with IC50 of 2.1 μM.
Features Not a general deubiquitinase inhibitor. Has minimal inhibition on recombinant and cytosolic nonproteasomal cysteine deubiquitinases.
Targets
USP14 [1] UCHL5 [1]
2.1 μM
In vitro

b-AP15 inhibits the activity of two 19S regulatory-particle-associated deubiquitinases, ubiquitin C-terminal hydrolase 5 (UCHL5) and ubiquitin-specific peptidase 14 (USP14), resulting in accumulation of polyubiquitin. b-AP15 results in a dose-dependent accumulation of the UbG76V-YFP reporter with IC50 of 0.8 μM, indicating impaired proteasome degradation. b-AP15 (1 μM) results in rapid accumulation of polyubiquitinated proteins in human colon carcinoma HCT-116 cells. b-AP15 (2.2 μM) increases the amounts of the cyclin-dependent kinases CDKN1A and CDKNIB and the tumor suppressor TP53 in a dose-dependent manner without altering the amounts of ornithine decarboxylase 1 (ODC1) in HCT-116 cells. b-AP15 (1 μM) results in G2/M phase cell-cycle arrest in HCT-116 cells, consistent with the accumulation of cell-cycle inhibitors. b-AP15 treatment increases the number of hypodiploid cells and is associated with increased amounts of apoptotic markers, including activated caspase-3, caspase-cleaved poly-ADP ribose polymerase (PARP) and cytokeratin-18 (CK18). b-AP15 is more toxic to HCT-116 cells as compared to immortalized epithelial cells (hTERT-RPE1) or peripheral blood mononuclear cells. b-AP15 inhibits deubiquitinating activity using a variety of substrates, including Ub-AMC, Ub-GFP22, ubiquitinated p53-binding protein homolog (HDM2), and K48- and K63-linked ubiquitin tetramer chains. [1] b-AP15 is an inhibitor of the UPS that induced cell death via induction of the lysosomal apoptosis pathway in a cathepsin-D dependent manner. b-AP15 elicits characteristic UPS defects including the accumulation of ubiquitin conjugates and cell cycle inhibitors such as p21, p27 and the tumor suppressor p53. b-AP15 inhibits the deubiquitinase activity of both cysteine DUBs, with USP14 being slightly more sensitive than UCHL5. b-AP15 induces apoptosis in cells over-expressing the anti-apoptotic Bcl-2 protein and in cells lacking the p53 gene. [2] b-AP15 (1 μM) inhibits ATP-induced IL-1β release from LPS-primed peritoneal macrophages. b-AP15 (1 μM) reduces the levels of cell death induced by nigericin treatment in THP-1 cells. b-AP15 (1 μM) significantly reduces the numbers of ASC specks formed after nigericin treatment in LPS-primed THP-1 cells. [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
P388 cells NEDnN45EgXSxdH;4bYNqfHliYYPzZZk> MVXDfZRwfG:6aXPpeJkh[WejaX7zeEBufXKrbnWgVFM5QCClZXzsd{whUUN3ME2wMlA2KM7:TR?= M2TpXVEyOTdyNkS4
human HSC2 NH\JO|REgXSxdH;4bYNqfHliYYPzZZk> NGDVOHhEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBJW0N{IHL5JG1VXCCvZYToc4QtKEOFNUC9NE4xQTRizszN M2nnTlE4PDl7OEi1
HL60 cells M1vQXmN6fG:2b4jpZ4l1gSCjc4PhfS=> MUTDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDIUFYxKGOnbHzzJIlvKHC{ZYPlcoNmKG:oIGLQUWkyPjRyIHPvcpRicW6rbnegNVAmKG[ndHHsJIJwfmmwZTDz[ZJ2dSCkeTD0dplx[W5iYnz1[UBmgGOudYPpc44hfGW|dDygR2M2OD1yLkGzJO69VQ>? MVmxO|Q6QTh6NR?=
Molt 4/C8 cells MYnDfZRwfG:6aXPpeJkh[XO|YYm= MoPFR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUY9tfCB2L1O4JINmdGy|LDDJR|UxRTBwMUWg{txO M2TxOlEyOTdyNkS4
CEM cells NH3ZNGNEgXSxdH;4bYNqfHliYYPzZZk> NHfXTWJEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBETU1iY3XscJMtKEmFNUC9NE4zPiEQvF2= MoLQNVk5OTlzM{W=
L1210 cells MX3DfZRwfG:6aXPpeJkh[XO|YYm= NYf3UGJUS3m2b4TvfIlkcXS7IHHnZYlve3RibYXybY5mKExzMkGwJINmdGy|LDDJR|UxRTBwNEKg{txO MnGyNVEyPzB4NEi=
HSC4 cells M4XBeGN6fG:2b4jpZ4l1gSCjc4PhfS=> MVnDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDIV2M1KGOnbHzzJIJ6KE2WVDDt[ZRpd2RuIFPDOVA:OC53NjFOwG0> NX2wW2REOTd2OUm4PFU>
In vivo b-AP15 (5 mg/kg) shows significant antitumor activity in severe combined immunodeficiency (SCID) mice with FaDu squamous carcinoma xenografts. b-AP15 (5 mg/kg) significantly delays tumor onset in mice with HCT-116 colon carcinoma xenografts. [1]

Protocol (from reference)

Animal Research:

[1]

  • Animal Models: mice with HCT-116 colon carcinoma xenografts
  • Dosages: 5 mg/kg
  • Administration: intraperitoneal injection

Solubility (25°C)

In vitro

DMSO 48 mg/mL warmed
(114.45 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
4% DMSO+corn oil
For best results, use promptly after mixing.

1mg/mL

Chemical Information

Molecular Weight 419.39
Formula

C22H17N3O6

CAS No. 1009817-63-3
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C=CC(=O)N1CC(=CC2=CC=C(C=C2)[N+](=O)[O-])C(=O)C(=CC3=CC=C(C=C3)[N+](=O)[O-])C1

In vivo Formulation Calculator (Clear solution)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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