milademetan   Click here for help

GtoPdb Ligand ID: 12941

Synonyms: DS-3032 | DS-3032B [3] | DS3032 | DS3032b | RAIN-32 [3]
Compound class: Synthetic organic
Comment: Milademetan (DS-3032) is an oral MDM2-p53 PPI inhibitor [2-3,6]. Based on evidence that inhibition of MDM2 can enhance p53 availability/function and potentiate cancer cell apoptosis, milademetan was developed as a potential cancer therapeutic [1-2,4].
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 9
Hydrogen bond donors 4
Rotatable bonds 5
Topological polar surface area 134.91
Molecular weight 618.53
XLogP 1.56
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

✖
Canonical SMILES CC1(C)CCC2(CC1)[C@]3(C4=CC=C(C=C4NC3=O)Cl)[C@@H](C5=CC=NC(=C5F)Cl)[C@H](C(=O)N[C@@H]6CC[C@@H](C(=O)N)OC6)N2
Isomeric SMILES CC1(CCC2(CC1)[C@@]3([C@H]([C@@H](N2)C(=O)N[C@@H]4CC[C@H](OC4)C(=O)N)C5=C(C(=NC=C5)Cl)F)C6=C(C=C(C=C6)Cl)NC3=O)C
InChI InChI=1S/C30H34Cl2FN5O4/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/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)/t16-,20+,21+,23-,30-/m1/s1
InChI Key RYAYYVTWKAOAJF-QISPRATLSA-N
No information available.
Summary of Clinical Use Click here for help
Milademetan (DS-3032, RAIN-32) is in clinical development as a treatment for leukemia [7-8] and selected advanced solid tumours [5].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03614455 Pharmacokinetics (PK) Drug Interaction Study of Milademetan and Itraconazole or Posaconazole in Healthy Participants Early Phase 1 Interventional Daiichi Sankyo, Inc.
NCT03634228 Milademetan Tosylate and Low-Dose Cytarabine With or Without Venetoclax in Treating Participants With Recurrent or Refractory Acute Myeloid Leukemia Phase 1/Phase 2 Interventional M.D. Anderson Cancer Center 8
NCT04979442 Treatment of Milademetan Versus Trabectedin in Patient With Dedifferentiated Liposarcoma Phase 3 Interventional Rain Oncology Inc
NCT05012397 Milademetan in Advanced/Metastatic Solid Tumors Phase 2 Interventional Rain Oncology Inc