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Details

Stereochemistry ABSOLUTE
Molecular Formula C30H34Cl2FN5O4.C7H8O3S.H2O
Molecular Weight 808.743
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MILADEMETAN TOSYLATE MONOHYDRATE

SMILES

O.CC1=CC=C(C=C1)S(O)(=O)=O.CC2(C)CCC3(CC2)N[C@H]([C@H](C4=C(F)C(Cl)=NC=C4)[C@]35C(=O)NC6=C5C=CC(Cl)=C6)C(=O)N[C@@H]7CC[C@H](OC7)C(N)=O

InChI

InChIKey=WPJOGWGXMTUHPW-CIPNXXNHSA-N
InChI=1S/C30H34Cl2FN5O4.C7H8O3S.H2O/c1-28(2)8-10-29(11-9-28)30(18-5-3-15(31)13-19(18)37-27(30)41)21(17-7-12-35-24(32)22(17)33)23(38-29)26(40)36-16-4-6-20(25(34)39)42-14-16;1-6-2-4-7(5-3-6)11(8,9)10;/h3,5,7,12-13,16,20-21,23,38H,4,6,8-11,14H2,1-2H3,(H2,34,39)(H,36,40)(H,37,41);2-5H,1H3,(H,8,9,10);1H2/t16-,20+,21+,23-,30-;;/m1../s1

HIDE SMILES / InChI

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C30H34Cl2FN5O4
Molecular Weight 618.526
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula C7H8O3S
Molecular Weight 172.202
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

DS-3032 (Milademetan) is an orally available, potent and selective inhibitor of the p53-MDM2 (murine double minute 2) interaction. Milademetan binds to, and prevents the binding of MDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53. Milademetan is 10-fold more potent than the first-generation inhibitor nutlin-3a. By preventing this MDM2-p53 interaction, the proteasome-mediated enzymatic degradation of p53 is inhibited and the transcriptional activity of p53 is restored. This results in the restoration of p53 signaling and leads to the p53-mediated induction of tumor cell apoptosis. DS-3032 is currently being evaluated in three phase 1 clinical trials for solid and hematological malignancies, including acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML) in blast phase, lymphoma and myelodysplastic syndrome (MDS).

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
PubMed

PubMed

TitleDatePubMed
Patents

Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: Mice data
4 days of daily treatment with gavages of 50 mg/kg followed by 2 days without treatment for 30 consecutive days.
Route of Administration: Oral
Substance Class Chemical
Created
by admin
on Sat Dec 16 13:17:26 GMT 2023
Edited
by admin
on Sat Dec 16 13:17:26 GMT 2023
Record UNII
4Y0K58UFU2
Record Status Validated (UNII)
Record Version
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Name Type Language
MILADEMETAN TOSYLATE MONOHYDRATE
Common Name English
DS-3032 TOSYLATE MONOHYDRATE
Common Name English
(3'R,4'S,5'R)-N-((3R,6S)-6-CARBAMOYLTETRAHYDRO-2H-PYRAN-3-YL)-6''-CHLORO-4'-(2-CHLORO-3-FLUOROPYRIDIN-4-YL)-4,4-DIMETHYL-2''-OXO-1'',2''-DIHYDRODISPIRO(CYCLOHEXANE-1,2'-PYRROLIDINE-3',3''-INDOLE)-5'-CARBOXAMIDE MONO(4-METHYLBENZENESULFONATE) MONOHYDRATE
Systematic Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 555416
Created by admin on Sat Dec 16 13:17:27 GMT 2023 , Edited by admin on Sat Dec 16 13:17:27 GMT 2023
EU-Orphan Drug EU/3/17/1847
Created by admin on Sat Dec 16 13:17:27 GMT 2023 , Edited by admin on Sat Dec 16 13:17:27 GMT 2023
Code System Code Type Description
FDA UNII
4Y0K58UFU2
Created by admin on Sat Dec 16 13:17:27 GMT 2023 , Edited by admin on Sat Dec 16 13:17:27 GMT 2023
PRIMARY
PUBCHEM
89051550
Created by admin on Sat Dec 16 13:17:27 GMT 2023 , Edited by admin on Sat Dec 16 13:17:27 GMT 2023
PRIMARY
SMS_ID
100000177988
Created by admin on Sat Dec 16 13:17:27 GMT 2023 , Edited by admin on Sat Dec 16 13:17:27 GMT 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
ANHYDROUS->SOLVATE
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ACTIVE MOIETY