U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C38H48Cl2N4O4S
Molecular Weight 727.783
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RO-5045337

SMILES

CCOC1=CC(=CC=C1C2=N[C@@](C)(C3=CC=C(Cl)C=C3)[C@](C)(N2C(=O)N4CCN(CCCS(C)(=O)=O)CC4)C5=CC=C(Cl)C=C5)C(C)(C)C

InChI

InChIKey=QBGKPEROWUKSBK-QPPIDDCLSA-N
InChI=1S/C38H48Cl2N4O4S/c1-8-48-33-26-29(36(2,3)4)14-19-32(33)34-41-37(5,27-10-15-30(39)16-11-27)38(6,28-12-17-31(40)18-13-28)44(34)35(45)43-23-21-42(22-24-43)20-9-25-49(7,46)47/h10-19,26H,8-9,20-25H2,1-7H3/t37-,38+/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26210682 | https://clinicaltrials.gov/ct2/show/NCT01605526 | https://www.ncbi.nlm.nih.gov/pubmed/26459177

RO-5045337 (RG7112) is a small molecule that binds to a MDM2, a negative regulator of tumor-supressor protein p53. It was discovered by Roche and investigated in clinical trials against solid tumors, leukemias and sarcomas.

Originator

Hoffman-La Roche
134
Curator's Comment: # Hoffman La Roche

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 18.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase I
428
Unknown

Approved Use

Unknown
Primary
Phase I
428
Unknown

Approved Use

Unknown
Primary
Phase I
428
Unknown

Approved Use

Unknown
Primary
Phase I
428
Unknown

Approved Use

Unknown
Primary
Phase I
428
Unknown

Approved Use

Unknown
Primary
Phase I
428
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
8943 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26459177
1500 mg 2 times / day steady-state, oral
dose: 1500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RO-5045337 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
5646.7 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26459177
1920 mg/m² 2 times / day steady-state, oral
dose: 1920 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RO-5045337 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
175528.9 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26459177
1500 mg 2 times / day steady-state, oral
dose: 1500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RO-5045337 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
89972.3 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26459177
1920 mg/m² 2 times / day steady-state, oral
dose: 1920 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RO-5045337 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
41.1 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26459177
1500 mg 2 times / day steady-state, oral
dose: 1500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RO-5045337 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
17.2 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/26459177
1920 mg/m² 2 times / day steady-state, oral
dose: 1920 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RO-5045337 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1920 mg/m2 2 times / day multiple, oral
Highest studied dose
Dose: 1920 mg/m2, 2 times / day
Route: oral
Route: multiple
Dose: 1920 mg/m2, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26459177
Page: p.7
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/26459177
Page: p.7
Sources:
https://pubmed.ncbi.nlm.nih.gov/26459177
Page: p.7
1500 mg 2 times / day multiple, oral
MTD
Dose: 1500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1500 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26459177
Page: p.7
unhealthy, ADULT
n = 30
Health Status: unhealthy
Condition: leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 30
Sources:
https://pubmed.ncbi.nlm.nih.gov/26459177
Page: p.7
Sources:
https://pubmed.ncbi.nlm.nih.gov/26459177
Page: p.7
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737

inhibitor
1587

OverviewOther

Other InhibitorOther SubstrateOther Inducer
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1925
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1737
 yes
PubMed

PubMed

TitleDatePubMed
Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development.
2013 May 9
Clinical pharmacology characterization of RG7112, an MDM2 antagonist, in patients with advanced solid tumors.
2015 Sep
Results of the Phase I Trial of RG7112, a Small-Molecule MDM2 Antagonist in Leukemia.
2016 Feb 15
Patents

Patents

US-7851626-B2
1

Sample Use Guides

In Vivo Use Guide
In leukemia study the starting dose was 20 mg/m2 of the crystalline formulation of RO-5045337, administered orally once-daily (QD). RO-5045337 was dosed orally for 10 days followed by 18 days of rest in a 28-day cycle.
Route of Administration: Oral
In Vitro Use Guide
To assess the potency of RO-5045337 as inhibitor of the p53-MDM2 interaction, a homogeneous time-resolved fluorescence (HTRF) assay that utilizes the N-terminal domain of recombinant human MDM2 protein and a peptide derived from the binding site of p53 was used. RO-5045337 inhibited binding of a model peptide with MDM2 with IC50 of 18 nM.
Name Type Language
RO-5045337
Code English
R 7112
Code English
METHANONE, ((4S,5R)-4,5-BIS(4-CHLOROPHENYL)-2-(4-(1,1-DIMETHYLETHYL)-2-ETHOXYPHENYL)-4,5-DIHYDRO-4,5-DIMETHYL-1H-IMIDAZOL-1-YL)(4-(3-(METHYLSULFONYL)PROPYL)-1-PIPERAZINYL)-
Common Name English
RG-7112
Code English
RO5045337
Code English
R 7112 [WHO-DD]
Common Name English
RG7112
Code English
MDM2 ANTAGONIST RO5045337
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C129839
Created by admin on Sat Dec 16 05:32:57 GMT 2023 , Edited by admin on Sat Dec 16 05:32:57 GMT 2023
Code System Code Type Description
SMS_ID
100000175235
Created by admin on Sat Dec 16 05:32:57 GMT 2023 , Edited by admin on Sat Dec 16 05:32:57 GMT 2023
PRIMARY
DRUG BANK
DB14793
Created by admin on Sat Dec 16 05:32:57 GMT 2023 , Edited by admin on Sat Dec 16 05:32:57 GMT 2023
PRIMARY
FDA UNII
Q8MI0X869M
Created by admin on Sat Dec 16 05:32:57 GMT 2023 , Edited by admin on Sat Dec 16 05:32:57 GMT 2023
PRIMARY
NCI_THESAURUS
C91724
Created by admin on Sat Dec 16 05:32:57 GMT 2023 , Edited by admin on Sat Dec 16 05:32:57 GMT 2023
PRIMARY
EPA CompTox
DTXSID60240182
Created by admin on Sat Dec 16 05:32:57 GMT 2023 , Edited by admin on Sat Dec 16 05:32:57 GMT 2023
PRIMARY
CAS
939981-39-2
Created by admin on Sat Dec 16 05:32:57 GMT 2023 , Edited by admin on Sat Dec 16 05:32:57 GMT 2023
PRIMARY
PUBCHEM
57406853
Created by admin on Sat Dec 16 05:32:57 GMT 2023 , Edited by admin on Sat Dec 16 05:32:57 GMT 2023
PRIMARY
ACTIVE MOIETY
Structure of RO-5045337
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966