CBPD-268   Click here for help

GtoPdb Ligand ID: 13245

Synonyms: CBPD268 | compound 33 [PMID: 38477974]
Compound class: Synthetic organic
Comment: CBPD-268 is an orally bioactive CBP/p300 PROTAC degrader [1]. The target protein binding component is based on the chemical structure of the CBP/p300 bromodomain inhibitor GNE-049. A new cereblon-binding ligand (TX-16; compound 27 in [2]) is incorporated to engage the E3 ubiquitin ligase.
CBP and p300 are transcriptional coactivators of the androgen receptor (AR) that are found to be abberantly expressed in prostate cancer, and to confer resistance to AR-targeted prostate cancer therapies. CBPD-268 is therefore proposed as an anti-prostate cancer strategy.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 14
Hydrogen bond donors 1
Rotatable bonds 8
Topological polar surface area 141.54
Molecular weight 819.9
XLogP 1.87
No. Lipinski's rules broken 2
SMILES / InChI / InChIKey
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Canonical SMILES CC(=O)N1CCC2=C(C1)C(=NN2[C@H]3CC[C@@H](CC3)CN4CC5=C(C=C6C(=C5)C(=O)N(C7CCC(=O)NC7=O)C6=O)C4)N8CCCC9=C8C=C(C(=C9)C%10=NN(C)C=C%10)C(F)F
Isomeric SMILES CC(N1CC2=C(N(N=C2N3CCCC4=C3C=C(C(C5=NN(C)C=C5)=C4)C(F)F)[C@H]6CC[C@H](CN7CC8=CC9=C(C=C8C7)C(N(C9=O)C%10CCC(NC%10=O)=O)=O)CC6)CC1)=O
InChI InChI=1S/C44H47F2N9O5/c1-24(56)52-15-12-36-34(23-52)41(53-13-3-4-26-16-30(35-11-14-50(2)48-35)31(40(45)46)19-38(26)53)49-55(36)29-7-5-25(6-8-29)20-51-21-27-17-32-33(18-28(27)22-51)44(60)54(43(32)59)37-9-10-39(57)47-42(37)58/h11,14,16-19,25,29,37,40H,3-10,12-13,15,20-23H2,1-2H3,(H,47,57,58)/t25-,29-,37?
InChI Key ZAGZYDLBQICBCA-UUOOYTBASA-N
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
cereblon Hs None Binding 5.7 pIC50 - 1
pIC50 5.7 (IC50 1.8x10-6 M) [1]
Selectivity at other protein targets
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
E1A binding protein p300 Hs None Binding 8.0 pIC50 - 1
pIC50 8.0 (IC50 9.5x10-9 M) PROTAC [1]
CREB binding protein Hs None Binding 8.0 pIC50 - 1
pIC50 8.0 (IC50 1.1x10-8 M) PROTAC [1]