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Details

Stereochemistry ABSOLUTE
Molecular Formula C31H29Cl2F2N3O4
Molecular Weight 616.482
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of IDASANUTLIN

SMILES

COC1=CC(=CC=C1NC(=O)[C@@H]2N[C@@H](CC(C)(C)C)[C@@](C#N)([C@H]2C3=CC=CC(Cl)=C3F)C4=CC=C(Cl)C=C4F)C(O)=O

InChI

InChIKey=TVTXCJFHQKSQQM-LJQIRTBHSA-N
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

HIDE SMILES / InChI

Molecular Formula C31H29Cl2F2N3O4
Molecular Weight 616.482
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including

Idasanutlin (RG-7388) is a second-generation, orally bioavailable, selective p53-MDM2 antagonist. MDM2 is an important negative regulator of the p 53 tumor suppressor and is expressed at high levels in a large proportion of acute myeloid leukemia (AML). Blocking the MDM2-p53 interaction stabilizes p53 and activates p-53 mediated cell death and inhibition cell growth. Idasanutlin is under clinical trial in phase III for treatment AML and in combinations with others drugs in phase I/II for treatment of multiple myeloma.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
800 mg 2 times / day multiple, oral
Highest studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 800 mg, 2 times / day
Sources: Page: p.3, 4
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: acute myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.3, 4
DLT: Bone marrow failure...
Other AEs: Diarrhea...
Dose limiting toxicities:
Bone marrow failure (grade 3, 8.3%)
Other AEs:
Diarrhea (grade 3-4, 50%)
Sources: Page: p.3, 4
AEs

AEs

AESignificanceDosePopulation
Bone marrow failure grade 3, 8.3%
DLT
800 mg 2 times / day multiple, oral
Highest studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 800 mg, 2 times / day
Sources: Page: p.3, 4
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: acute myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.3, 4
Diarrhea grade 3-4, 50%
800 mg 2 times / day multiple, oral
Highest studied dose
Dose: 800 mg, 2 times / day
Route: oral
Route: multiple
Dose: 800 mg, 2 times / day
Sources: Page: p.3, 4
unhealthy, ADULT
n = 12
Health Status: unhealthy
Condition: acute myeloid leukemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.3, 4
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer





Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
major
yes (co-administration study)
Comment: Posaconazole reduced Cmax by 6.5% and increased AUCinf by 31%.
yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Superior anti-tumor activity of the MDM2 antagonist idasanutlin and the Bcl-2 inhibitor venetoclax in p53 wild-type acute myeloid leukemia models.
2016 Jun 28
Acute myeloid leukemia patients' clinical response to idasanutlin (RG7388) is associated with pre-treatment MDM2 protein expression in leukemic blasts.
2016 May
Antitumour activity of the glycoengineered type II anti-CD20 antibody obinutuzumab (GA101) in combination with the MDM2-selective antagonist idasanutlin (RG7388).
2016 Nov
Patents

Sample Use Guides

Idasanutlin plus Cytarabine. Participants are treated with 300 mg idasanutlin administered orally twice daily and intravenous cytarabine once daily for 5 days followed by 23 days of rest (Cycle 1). Responding patients may continue to receive a maximum of further two cycles of consolidation (Cycle 2 and Cycle 3).
Route of Administration: Oral
Acute myeloid leukemia (AML) cell cultures were treated with idasanutlin alone (0.6–2000nM) or in combination with venetoclax. Combination treatment results in synergistic anti-tumor activity compared with the respective single-agent treatments in vitro, in p53 wild-type AML cell lines, and leads to strongly superior efficacy in vivo, in subcutaneous and orthotopic AML models. The inhibitory effects of idasanutlin were cell-cycle dependent, with cells arresting in G1 in consecutive cycles and the induction of apoptosis only evident after cells had gone through at least two cell cycles.
Substance Class Chemical
Created
by admin
on Thu Jul 06 15:42:20 UTC 2023
Edited
by admin
on Thu Jul 06 15:42:20 UTC 2023
Record UNII
QSQ883V35U
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
IDASANUTLIN
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
idasanutlin [INN]
Common Name English
RO-5503781
Code English
RO5503781
Code English
BENZOIC ACID, 4-((((2R,3S,4R,5S)-3-(3-CHLORO-2-FLUOROPHENYL)-4-(4-CHLORO-2-FLUOROPHENYL)-4-CYANO-5-(2,2-DIMETHYLPROPYL)-2-PYRROLIDINYL)CARBONYL)AMINO)-3-METHOXY-
Systematic Name English
IDASANUTLIN [USAN]
Common Name English
RG7388
Code English
RG-7388
Code English
Idasanutlin [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C274
Created by admin on Thu Jul 06 15:42:20 UTC 2023 , Edited by admin on Thu Jul 06 15:42:20 UTC 2023
FDA ORPHAN DRUG 664118
Created by admin on Thu Jul 06 15:42:20 UTC 2023 , Edited by admin on Thu Jul 06 15:42:20 UTC 2023
FDA ORPHAN DRUG 615017
Created by admin on Thu Jul 06 15:42:20 UTC 2023 , Edited by admin on Thu Jul 06 15:42:20 UTC 2023
FDA ORPHAN DRUG 429614
Created by admin on Thu Jul 06 15:42:20 UTC 2023 , Edited by admin on Thu Jul 06 15:42:20 UTC 2023
EU-Orphan Drug EU/3/14/1328
Created by admin on Thu Jul 06 15:42:20 UTC 2023 , Edited by admin on Thu Jul 06 15:42:20 UTC 2023
Code System Code Type Description
NCI_THESAURUS
C99131
Created by admin on Thu Jul 06 15:42:20 UTC 2023 , Edited by admin on Thu Jul 06 15:42:20 UTC 2023
PRIMARY
ChEMBL
CHEMBL2402737
Created by admin on Thu Jul 06 15:42:20 UTC 2023 , Edited by admin on Thu Jul 06 15:42:20 UTC 2023
PRIMARY
CAS
1229705-06-9
Created by admin on Thu Jul 06 15:42:20 UTC 2023 , Edited by admin on Thu Jul 06 15:42:20 UTC 2023
PRIMARY
DRUG BANK
DB12325
Created by admin on Thu Jul 06 15:42:20 UTC 2023 , Edited by admin on Thu Jul 06 15:42:20 UTC 2023
PRIMARY
PUBCHEM
53358942
Created by admin on Thu Jul 06 15:42:20 UTC 2023 , Edited by admin on Thu Jul 06 15:42:20 UTC 2023
PRIMARY
INN
9920
Created by admin on Thu Jul 06 15:42:20 UTC 2023 , Edited by admin on Thu Jul 06 15:42:20 UTC 2023
PRIMARY
SMS_ID
100000172696
Created by admin on Thu Jul 06 15:42:20 UTC 2023 , Edited by admin on Thu Jul 06 15:42:20 UTC 2023
PRIMARY
EPA CompTox
DTXSID001025954
Created by admin on Thu Jul 06 15:42:20 UTC 2023 , Edited by admin on Thu Jul 06 15:42:20 UTC 2023
PRIMARY
FDA UNII
QSQ883V35U
Created by admin on Thu Jul 06 15:42:20 UTC 2023 , Edited by admin on Thu Jul 06 15:42:20 UTC 2023
PRIMARY
USAN
CD-99
Created by admin on Thu Jul 06 15:42:20 UTC 2023 , Edited by admin on Thu Jul 06 15:42:20 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Ki
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ACTIVE MOIETY