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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
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
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