GtoPdb is requesting financial support from commercial users. Please see our sustainability page for more information.

PRT3789   Click here for help

GtoPdb Ligand ID: 13837

Synonyms: compound 1 [WO2024076985A2] [2] | PRT-3789
Compound class: Synthetic organic
Comment: The structure presented here is claimed in patent WO2024076985A2 as a SMARCA2-selective degrader [2]. This same chemical structure was disclosed as Prelude Therapeutics' PRT3789 during the 'First Time disclosures' session at the ACS Spring 2025 meeting in San Diego. In patent US20240018158A1 Prelude Therapeutics claim degraders that interact with the SMARCA2 bromodomain, and E3 ubiquitin ligase to promote ubiquitin-mediated degradation. PRT3789 is one of these claims, although it difficult to ascertain which of the exemplar compounds is the exact stereoisomeric match to PRT3789. PRT3789 utilises a VHL-based E3 ligase binding moiety.
In therapeutic terms, reducing/inhibiting SMARCA2 is considered as a novel anti-tumour intervention [1], notably to exploit synthetic lethality in cancers that are SMARA4 deficient and that switch dependence to SMARCA2 for survival.
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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 14
Hydrogen bond donors 4
Rotatable bonds 15
Topological polar surface area 204.82
Molecular weight 891.09
XLogP 4.36
No. Lipinski's rules broken 3

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

✖
Canonical SMILES CC(C)[C@H](C1=CC(=NO1)O[C@@H](C)CN2CC[C@H](C2)N3CCN4[C@@H](CNC5=NN=C(C=C54)C6=C(C=CC=C6)O)C3)C(=O)N7C[C@@H](C[C@H]7C(=O)N[C@@H](C)C8=CC=C(C=C8)C9=C(C)N=CS9)O
Isomeric SMILES CC(C)[C@H](C1=CC(=NO1)O[C@@H](C)CN2CC[C@H](C2)N3CCN4[C@@H](CNC5=C4C=C(C6=C(C=CC=C6)O)N=N5)C3)C(=O)N7C[C@@H](C[C@H]7C(=O)N[C@@H](C)C8=CC=C(C=C8)C9=C(C)N=CS9)O
InChI InChI=1S/C47H58N10O6S/c1-27(2)43(47(61)57-25-35(58)18-39(57)46(60)50-29(4)31-10-12-32(13-11-31)44-30(5)49-26-64-44)41-20-42(53-63-41)62-28(3)22-54-15-14-33(23-54)55-16-17-56-34(24-55)21-48-45-38(56)19-37(51-52-45)36-8-6-7-9-40(36)59/h6-13,19-20,26-29,33-35,39,43,58-59H,14-18,21-25H2,1-5H3,(H,48,52)(H,50,60)/t28-,29-,33+,34-,35+,39-,43+/m0/s1
InChI Key OSRJAZPHBNGCLU-CMMQWICPSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
PRT3789 is a clinical candidate for the treatment of timours harbouring SMARCA4 mutations. It is being investigated in combination with other anti-tumour therapies.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT05639751 PRT3789 Monotherapy and in Combo w/Docetaxel in Participants w/Advanced or Metastatic Solid Tumors w/SMARCA4 Mutation Phase 1 Interventional Prelude Therapeutics
NCT06682806 A Study of PRT3789 in Combination With Pembrolizumab in Patients With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation Phase 2 Interventional Prelude Therapeutics