1. Apoptosis
  2. RIP kinase
  3. RIPA-56

RIPA-56 

Cat. No.: HY-101032 Purity: 99.86%
Handling Instructions

RIPA-56 is a highly potent, selective, and metabolically stable inhibitor of receptor-interacting protein 1 (RIP1) with an IC50 of 13 nM.

For research use only. We do not sell to patients.

RIPA-56 Chemical Structure

RIPA-56 Chemical Structure

CAS No. : 1956370-21-0

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 66 In-stock
Estimated Time of Arrival: December 31
10 mg USD 60 In-stock
Estimated Time of Arrival: December 31
50 mg USD 156 In-stock
Estimated Time of Arrival: December 31
100 mg USD 276 In-stock
Estimated Time of Arrival: December 31
200 mg USD 468 In-stock
Estimated Time of Arrival: December 31
500 mg   Get quote  
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  • Biological Activity

  • Protocol

  • Technical Information

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  • References

Description

RIPA-56 is a highly potent, selective, and metabolically stable inhibitor of receptor-interacting protein 1 (RIP1) with an IC50 of 13 nM.

IC50 & Target

IC50: 13 nM (RIP1)[1]

In Vitro

RIPA-56 has a half-life of 128 min in human liver microsomal stability assays and an EC50 of 28 nM in TSZ-induced HT-29 necrosis assay. RIPA-56 also demonstrates potency in protection of murine L929 cells from TZ-induced necrosis (EC50=27 nM). RIPA-56 shows efficient inhibition of RIP1 kinase activity, with an IC50 of 13 nM and no inhibition of RIP3 kinase activity at a 10 μM concentration. RIPA-56 could form tight hydrophobic interactions with RIP1 through both the phenyl group and the 2,2-dimethylbutyl group, and form two important hydrogen bonds[1].

In Vivo

In the SIRS mice disease model, RIPA-56 efficiently reduces tumor necrosis factor alpha (TNFα)-induced mortality and multi-organ damage. Compared to known RIP1 inhibitors, RIPA-56 is potent in both human and murine cells, is much more stable in vivo, and is efficacious in animal model studies. RIPA-56 has an impressive PK profile in mice with a 3.1 h half-life, 22% oral bioavailability (P.O.), and 100% bioavailability from intraperitoneal injection (I.P.)[1].

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : ≥ 100 mg/mL (451.88 mM)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 4.5188 mL 22.5938 mL 45.1875 mL
5 mM 0.9038 mL 4.5188 mL 9.0375 mL
10 mM 0.4519 mL 2.2594 mL 4.5188 mL
*Please refer to the solubility information to select the appropriate solvent.
In Vivo:
  • 1.

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2.5 mg/mL (11.30 mM); Clear solution

  • 2.

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.5 mg/mL (11.30 mM); Clear solution

  • 3.

    Add each solvent one by one:  10% DMSO    90% corn oil

    Solubility: ≥ 2.5 mg/mL (11.30 mM); Clear solution

*All of the co-solvents are provided by MCE.
References
Kinase Assay
[1]

The RIP1 kinase assay is performed in white 384-well plate. RIP1 is first incubated with RIPA-56 or DMSO control for 15 min, then ATP/MBP substrate mixture is added to initiate the reaction. The final concentration of ATP is 50 μM, and MBP 20 μM. After 90 min reaction at room temperature, the ADP-Glo reagent and detection solution are added. The RIP3 kinase assay conditions are almost identical to that of RIP1 assay, except the assay buffer contained 5 mM MgCl2 instead of 20 mM MgCl2 and 12.5 mM MnCl2. The luminescence is measured on PerkinElmer Enspire[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

Cell necrosis assay is performed in 96-well cell culture plate. 3,000 cells are plated in each well and cultured at 37°C overnight. HT-29 cells are treated with 20 ng/mL TNFα/100 nM Smac Mimetics/20 μM z-VAD-FMK and RIPA-56 for 24 h. L929 cells are treated with 20 ng/mL TNFα/20 μM z-VAD-FMK and RIPA-56 for 6 h. The cell survival ratio is determined using the Cell Titer-Glo Luminescent Cell Viability Assay kit[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

Mice: Following intraveneous (IV), intraperitoneal (IP), or oral administration (PO) of RIPA-56 to C57BL/6 mice (n=3), blood is sampled through eye puncture at various time points. Compound concentrations in the plasma samples are analyzed by LCMS/MS. Pharmacokinetic parameters are determined from individual animal data using noncompartmental analysis in phoenix 64[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

221.30

Formula

C₁₃H₁₉NO₂

CAS No.

1956370-21-0

SMILES

CCC(C)(C)C(N(CC1=CC=CC=C1)O)=O

Shipping

Room temperature in continental US; may vary elsewhere

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Product Name:
RIPA-56
Cat. No.:
HY-101032
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RIPA-56

Cat. No.: HY-101032