NUTLIN-3

Details

Stereochemistry	RACEMIC
Molecular Formula	C30H30Cl2N4O4
Molecular Weight	581.49
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC(OC(C)C)=C(C=C1)C2=N[C@H]([C@H](N2C(=O)N3CCNC(=O)C3)C4=CC=C(Cl)C=C4)C5=CC=C(Cl)C=C5

InChI

InChIKey=BDUHCSBCVGXTJM-WUFINQPMSA-N

InChI=1S/C30H30Cl2N4O4/c1-18(2)40-25-16-23(39-3)12-13-24(25)29-34-27(19-4-8-21(31)9-5-19)28(20-6-10-22(32)11-7-20)36(29)30(38)35-15-14-33-26(37)17-35/h4-13,16,18,27-28H,14-15,17H2,1-3H3,(H,33,37)/t27-,28+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C30H30Cl2N4O4
Molecular Weight	581.49
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14704432
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26858935 | https://www.ncbi.nlm.nih.gov/pubmed/20588277

Nutlins are cis-imidazoline analogs which inhibit the interaction between mdm2 and tumour suppressor p53. Inhibiting the interaction between mdm2 and p53 stabilizes p53, and is thought to selectively induce a growth-inhibiting state called senescence in cancer cells. These compounds are therefore thought to work best on tumors that contain normal or "wild-type" p53. Nutlin-3 does not induce the phosphorylation of p53 on key serine residues and reveals no difference in their sequence-specific DNA binding and ability to transactivate p53 target genes compared with phosphorylated p53 induced by the genotoxic drugs doxorubicin and etoposide, demonstrating that phosphorylation of p53 on key serines is dispensable for transcriptional activation and apoptosis.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tumour suppressor p53/oncoprotein Mdm2 6 Target ID: CHEMBL1907611 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14704432	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2578

PubMed

Title	Date	PubMed
		252160276
		252160534
In vivo activation of the p53 pathway by small-molecule antagonists of MDM2.	2004 Feb 6	14704432

Patents

Sample Use Guides

In Vivo Use Guide

Nude mice (10 animals per dose group) bearing subcutaneous human cancer xenografts (SJSA-1) received 200 mg/kg of an oral dose of Nutlin-3 (racemic) twice daily for 3 weeks.

Route of Administration: Oral

In Vitro Use Guide

Cancer cells with wild-type p53 (HCT116, RKO, and SJSA-1) and mutant p53 (MDA-MB-435 and SW480) were incubated with Nutlin-3 (0-30mkM) for 8 hours.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:11:44 GMT 2023` Edited by `admin` on `Sat Dec 16 08:11:44 GMT 2023`
Record UNII	53IA0V845C
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

NUTLIN-3

Common Name

English

2-PIPERAZINONE, 4-(((4R,5S)-4,5-BIS(4-CHLOROPHENYL)-4,5-DIHYDRO-2-(4-METHOXY-2-(1-METHYLETHOXY)PHENYL)-1H-IMIDAZOL-1-YL)CARBONYL)-, REL-

Systematic Name

English

NSC-732664

Code

English

Code System Code Type Description

CAS

548472-68-0