Name: Idasanutlin
Brand: BOC Sciences
Price: 399 USD
Availability: MadeToOrder

Purity

>98%

Appearance

Solid powder

Application

For research used only

Synonyms

RG7388; RG 7388; RG-7388; RO5503781; RO-5503781; RO 5503781

InChI Key

TVTXCJFHQKSQQM-LJQIRTBHSA-N

InChI

InChI=1S/C31H29Cl2F2N3O4/c1-30(2,3)14-24-31(15-36,19-10-9-17(32)13-21(19)34)25(18-6-5-7-20(33)26(18)35)27(38-24)28(39)37-22-11-8-16(29(40)41)12-23(22)42-4/h5-13,24-25,27,38H,14H2,1-4H3,(H,37,39)(H,40,41)/t24-,25-,27+,31-/m0/s1

Canonical SMILES

CC(C)(C)CC1C(C(C(N1)C(=O)NC2=C(C=C(C=C2)C(=O)O)OC)C3=C(C(=CC=C3)Cl)F)(C#N)C4=C(C=C(C=C4)Cl)F

Background Introduction

Idasanutlin is a potent, selective, small-molecule antagonist of the Murine Double Minute 2 (MDM2) protein. As part of the Nutlin family, Idasanutlin inhibits the MDM2-p53 protein-protein interaction, leading to reactivation of the p53 tumor suppressor pathway. Given its robust binding affinity and high selectivity, Idasanutlin is widely studied in oncology and increasingly leveraged in the design of innovative PROTAC molecules targeting the MDM2 E3 ligase system.

Mechanism

Idasanutlin functions by directly binding the p53-binding pocket on the MDM2 E3 ubiquitin ligase, thereby preventing the degradation of p53 mediated by MDM2. In a PROTAC context, Idasanutlin serves as a ligand for MDM2, recruiting this E3 ligase to the target protein of interest when linked via an appropriate chemical linker. This proximity enables ubiquitination of the target protein, leading to its selective proteasomal degradation. The use of Idasanutlin in PROTAC design facilitates the development of bifunctional molecules capable of modulating protein levels with high specificity.

Applications

Idasanutlin is widely used in the research and development of MDM2-based PROTACs, providing a viable E3 ligase recruitment strategy for targeted protein degradation. Its primary applications include:

• Design of bifunctional degraders for challenging or undruggable targets using MDM2 recruitment
• Mechanistic studies on p53 pathway modulation and E3 ligase-mediated TPD (targeted protein degradation)
• Screening platforms and drug discovery efforts focused on oncology and related therapeutic areas
• Optimization and SAR (structure-activity relationship) studies of MDM2 ligands as part of degrader and molecular glue libraries

Idasanutlin's robust performance and versatility make it a valuable tool for PROTAC research, chemical biology, and targeted therapeutics innovation.

• High-purity compound verified by HPLC, NMR, and LC-MS
• Consistent batch-to-batch reproducibility with complete QC documentation
• Supplied with COA, MSDS, and analytical data for traceability
• Reliable global shipping with stability-guaranteed packaging
• Dedicated technical support and optional custom synthesis service
• Demonstrates strong binding affinity to CRBN, VHL, or other E3 ligases
• Enables stable E3 ligase recruitment for targeted protein degradation
• Selective MDM2 inhibitor, making it an optimal warhead for PROTAC development targeting the p53-MDM2 interaction.
• High potency and well-characterized pharmacological profile facilitate efficient design of cancer-targeted therapeutics.

1.Antitumour activity of the glycoengineered type II anti-CD20 antibody obinutuzumab (GA101) in combination with the MDM2 selective antagonist idasanutlin (RG7388).

Herting F1, Herter S2, Friess T1, Muth G1, Bacac M2, Sulcova J2, Umana P2, Dangl M1, Klein C2. Eur J Haematol. 2016 Mar 19. doi: 10.1111/ejh.12756. [Epub ahead of print]

OBJECTIVES: To investigate whether the glycoengineered, type II anti-CD20 monoclonal antibody obinutuzumab (GA101) combined with the selective MDM2 antagonist idasanutlin (RG7388) offers superior efficacy to monotherapy in treating B-lymphoid malignancies in preclinical models METHODS: The combined effect of obinutuzumab or rituximab plus idasanutlin on direct cell death/apoptosis induction and antibody-dependent cellular cytotoxicity (ADCC) was evaluated using p53 wild-type Z-138 and DoHH-2 lymphoma cells. Furthermore, whole blood B-cell depletion was analysed, and tumour growth inhibition was evaluated in subcutaneous xenograft models RESULTS: Idasanutlin induced concentration-dependent death of Z-138 and DoHH-2 cells. At concentrations >10-100 nM, idasanutlin enhanced obinutuzumab-induced death of DoHH-2 and Z-138 cells without negatively impacting obinutuzumab-mediated ADCC, natural killer cell activation, or whole blood B-cell depletion.

2.Investigating the effect of autoinduction in cynomolgus monkeys of a novel anticancer MDM2 antagonist, idasanutlin, and relevance to humans.

Glenn KJ1,2, Yu LJ1, Reddy MB1,3, Fretland AJ1,4, Parrott N5, Hussain S1,6, Palacios M1,7, Vazvaei F1, Zhi J8, Tuerck D5. Xenobiotica. 2016 Aug;46(8):667-76. doi: 10.3109/00498254.2015.1110761. Epub 2015 Nov 19.

1. Idasanutlin (RG7388) is a potent p53-MDM2 antagonist currently in clinical development for treatment of cancer. The purpose of the present studies was to investigate the cause of marked decrease in plasma exposure after repeated oral administration of RG7388 in monkeys and whether the autoinduction observed in monkeys is relevant to humans. 2. In monkey liver and intestinal microsomes collected after repeated oral administration of RG7388 to monkeys, significantly increased activities of homologue CYP3A8 were observed (ex vivo). Investigation using a physiologically based pharmacokinetic (PBPK) model suggested that the loss of exposure was primarily due to induction of metabolism in the gut of monkeys. 3. Studies in monkey and human primary hepatocytes showed that CYP3A induction by RG7388 only occurred in monkey hepatocytes but not in human hepatocytes, which suggests the observed CYP3A induction is monkey specific. 4. The human PK data obtained from the first cohorts confirmed the lack of relevant induction as predicted by the human hepatocytes and the PBPK modelling based on no induction in humans.

ConcentrationVolumeMass	1 mg	5 mg	10 mg
1 mM	1.6221 mL	8.1106 mL	16.2211 mL
5 mM	0.3244 mL	1.6221 mL	3.2442 mL
10 mM	0.1622 mL	0.8111 mL	1.6221 mL
50 mM	0.0324 mL	0.1622 mL	0.3244 mL

HNMR

HPLC

Hello, please give information about the mechanism by which Idasanutlin damages tumor cells.

OK!Idasanutlin through blocking p53−MDM2 binding and effectively activates the p53 pathway, leading to cell cycle arrest and/or apoptosis in cell lines expressing wild-type p53 and tumor growth inhibition or regression of osteosarcoma xenografts in nude mice.

16/1/2016

Hi! May I know the current research status of Idasanutlin?

Yes! It is currently in three phase I clinical trials for treatment of patients with solid tumors, acute myelogenous leukemia, or advanced malignancies as a single agent and in combination with chemotherapeutics.

14/3/2020

Hi! please describe the PK properties about Idasanutlin.Thanks.

No thanks! In mice, it has oral bioavailability (80%), moderate clearance (t1/2 = 1.6 h).

30/3/2020

activates the p53 pathway

Idasanutlin blocks p53–MDM2 binding and effectively activates the p53 pathway.It worked as expected.

24/8/2018

MDM2 inhibitor

Used in our lab, no complaints, worked well. all the characteristics expected of an MDM2 inhibitor in terms of specific binding to the target, mechanistic outcomes resulting from activation of the p53 pathway, and in vivo efficacy.

10/1/2019

tumor growth inhibition

Recommend everyone to use. Idasanutlin shows tumor growth inhibition and regression of osteosarcoma xenografts in nude mice.

18/4/2020

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* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂