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

WWL0245   Click here for help

GtoPdb Ligand ID: 12142

Synonyms: BRD4-PROTAC 12a | WWL-0245
Compound class: Synthetic organic
Comment: WWL0245 is a bifunctional cereblon-based PROTAC molecule that promotes ubiquitin-proteasomal degradation of BRD4 protein [1]. The BET domain-binding region is based on the dual BET/PLK1 inhibitor WNY0824. Cereblon binding is mediated via a modified thalidomide moiety. WWL0245 exhibits selective cytotoxicity in BET inhibitor sensitive cancer cell lines such as androgen receptor (AR)-positive prostate cancer cell lines, and it promotes a more potent anti-proliferative effect than the parent BET inhibitor.
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 16
Hydrogen bond donors 3
Rotatable bonds 14
Topological polar surface area 222.66
Molecular weight 873.39
XLogP 6.63
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 COc1cc(ccc1Nc1ncc2c(n1)N(CC1CCCCC1)[C@@H](c1n2c(C)nn1)CC)C(=O)NC1CCN(CC1)C(=O)COc1cccc2c1C(=O)N(C2=O)C1CCC(=O)NC1=O
Isomeric SMILES C1(CCCCC1)CN1[C@@H](c2n(c3cnc(nc13)Nc1c(cc(C(=O)NC3CCN(CC3)C(=O)COc3c4C(=O)N(C(=O)c4ccc3)C3C(=O)NC(=O)CC3)cc1)OC)c(nn2)C)CC
InChI InChI=1S/C45H51N11O8/c1-4-31-40-52-51-25(2)55(40)33-22-46-45(50-39(33)54(31)23-26-9-6-5-7-10-26)48-30-14-13-27(21-35(30)63-3)41(59)47-28-17-19-53(20-18-28)37(58)24-64-34-12-8-11-29-38(34)44(62)56(43(29)61)32-15-16-36(57)49-42(32)60/h8,11-14,21-22,26,28,31-32H,4-7,9-10,15-20,23-24H2,1-3H3,(H,47,59)(H,46,48,50)(H,49,57,60)/t31-,32?/m1/s1
InChI Key AORZPRLVKUMTOJ-XGDNGBMYSA-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/)
References
1. Hu R, Wang WL, Yang YY, Hu XT, Wang QW, Zuo WQ, Xu Y, Feng Q, Wang NY. (2022)
Identification of a selective BRD4 PROTAC with potent antiproliferative effects in AR-positive prostate cancer based on a dual BET/PLK1 inhibitor.
Eur J Med Chem, 227: 113922. [PMID:34700270]