RG-4733

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H20F5N3O3
Molecular Weight	469.4045
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(C(=O)NCC(F)(F)C(F)(F)F)C(=O)N[C@H]1C2=C(C=CC=C2)C3=C(NC1=O)C=CC=C3

InChI

InChIKey=OJPLJFIFUQPSJR-INIZCTEOSA-N

InChI=1S/C22H20F5N3O3/c1-20(2,18(32)28-11-21(23,24)22(25,26)27)19(33)30-16-14-9-4-3-7-12(14)13-8-5-6-10-15(13)29-17(16)31/h3-10,16H,11H2,1-2H3,(H,28,32)(H,29,31)(H,30,33)/t16-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C22H20F5N3O3
Molecular Weight	469.4045
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25250858
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27826680 | https://www.ncbi.nlm.nih.gov/pubmed/24668033

RO4929097 (R-4733) is a small-molecule inhibitor of gamma-secretase (γ-secretase) with high oral bioavailability leading to the blockade of Notch signaling in tumor cells. This compound was co-developed by Roche and National Cancer Institute (NCI). RO4929097 had been in phase II clinical trials for the treatment of melanoma, colorectal cancer, and pancreatic cancer. However, these researches has been discontinued. Combination of RO4929097 and bevacizumab was well tolerated in phase I of clinical trial and can be considered in patients with recurrent malignant glioma.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
gamma-secretase 1 Target ID: gamma-secretase Sources: https://www.ncbi.nlm.nih.gov/pubmed/19773430	Inhibitor 8297		4.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Melanoma 88 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25250858	Primary	Phase II 1132	Unknown Approved Use Unknown
Malignant glioma 10 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27826680	Primary	Phase I 428	Unknown Approved Use Unknown
Metastatic pancreatic adenocarcinoma 5 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24668033	Primary	Phase II 1132	Unknown Approved Use Unknown
Metastatic colorectal cancer 14 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22445247	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
498.1 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22351688	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		RG-4733 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
6034.5 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22351688	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		RG-4733 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
24.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22351688	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		RG-4733 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1.2% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22351688	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		RG-4733 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P003ASY	https://www.1pchem.com/search?query=1P003ASY
AChemBlock	10248	http://www.achemblock.com/catalogsearch/result/?q=10248
AK Scientific	X7559	https://aksci.com/item_detail.php?cat=X7559
Angene	AGN-PC-0UTYA6	http://www.angenechemical.com/productshow/AGN-PC-0UTYA6.html
ApexBio Technology	A4005	https://www.apexbt.com/catalogsearch/result/?q=A4005
AstaTech	C76705	http://astatechinc.com/CPSResult.php?CRNO=C76705
Axon MedChem	2521	https://www.axonmedchem.com/product/2521
BLD Pharm	BD305998	http://www.bldpharm.com/search/Search.html?keyword=BD305998
BOC Sciences	847925-91-1	http://www.bocsci.com/description.asp?cas=847925-91-1
Cayman Chemical	19996	http://www.caymanchem.com/app/template/Product.vm/catalog/19996
Chem Scene	CS-0480	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0480
ChemShuttle	111916	https://www.chemshuttle.com/catalogsearch/result/?q=111916
Excenen	EX-A1750	http://www.excenen.com/searchresultlist.php?id=EX-A1750
KeyOrganics	AS-74989	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-74989
Lab Seeker	SC-85823	http://www.labseeker.com/search.php?keywords=SC-85823&category=0
LabSeeker	SC-85823	http://www.labseeker.com/search.php?keywords=SC-85823&category=0
Matrix Scientific	132571	http://www.matrixscientific.com/132571.html
MedChem Express	HY-11102	https://www.medchemexpress.com/search.html?q=HY-11102&ft=&fa=&fp=
MolPort	MolPort-016-633-243	https://www.molport.com/shop/molecule-link/MolPort-016-633-243
Molnova	M16154	https://www.molnova.com/en/serch-list.html?keywords=M16154
MuseChem	I005077	https://www.musechem.com/product/I005077.html
ShangHai Biochempartner	BCP000438	http://www.biochempartner.com/search_BCP000438
TargetMol	T6274	https://www.targetmol.com/search?keyword=T6274
W&J PharmaChem	50C1413682	http://wjpharmachem.com/new/searcht.php?keyword=50C1413682
eMolecules	300525595	https://orderbb.emolecules.com/search/#?query=300525595
eMolecules	32278086	https://orderbb.emolecules.com/search/#?query=32278086
eMolecules	36730022	https://orderbb.emolecules.com/search/#?query=36730022
eNovation Chemicals	D372566	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D372566&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-5281659775	https://mcule.com/MCULE-5281659775/
mcule	MCULE-9974480964	https://mcule.com/MCULE-9974480964/

PubMed

Title	Date	PubMed
Phase I study of RO4929097, a gamma secretase inhibitor of Notch signaling, in patients with refractory metastatic or locally advanced solid tumors.	2012 Jul 1	22529266
A phase II study of RO4929097 in metastatic colorectal cancer.	2012 May	22445247

Patents

Sample Use Guides

In Vivo Use Guide

RO4929097 at a dose of 20 mg daily 3 consecutive days per week.

Route of Administration: Oral

In Vitro Use Guide

RO4929097 decreases the amount of Aβ peptides secreted into the culture medium in HEK293 cells with EC50 of 14 nM also strongly inhibits Notch processing with EC50 of 5 nM in the Notch cell-based reporter assay. The primary in vitro assay used human cell-free membrane preparations to provide the γ-secretase enzyme complex. RO4929097 strongly inhibited γ-secretase enzyme activity with a 4 nM potency. After 5 days of treatment, RO4929097 reduces the production of intracellular Notch (ICN) in the human NSCLC A549 cells inducing a flattened and less transformed tumor cell phenotype in tissue culture.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:39:28 GMT 2023` Edited by `admin` on `Fri Dec 15 16:39:28 GMT 2023`
Record UNII	KK8645V7LE
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

RG-4733

Common Name

English

RO-4929097

Code

English

PROPANEDIAMIDE, N1-((7S)-6,7-DIHYDRO-6-OXO-5H-DIBENZ(B,D)AZEPIN-7-YL)-2,2-DIMETHYL-N3-(2,2,3,3,3-PENTAFLUOROPROPYL)-

Systematic Name

English

RO 4929097

Code

English

PROPANEDIAMIDE, N-((7S)-6,7-DIHYDRO-6-OXO-5H-DIBENZ(B,D)AZEPIN-7-YL)-2,2-DIMETHYL-N'-(2,2,3,3,3-PENTAFLUOROPROPYL)-

Systematic Name

English

RG 4733 [WHO-DD]

Common Name

English

RO4929097

Common Name

English

Code System Code Type Description

CAS

847925-91-1