SMD-3040   Click here for help

GtoPdb Ligand ID: 12842

Synonyms: compound 29 [PMID: 37523716] | SMD3040
Compound class: Synthetic organic
Comment: SMD-3040 is an experimental SMARCA2 PROTAC degrader [1]. It uses a SMARCA2/4 bromodomain-binding ligand (SMARCA2/4 ligand 3 [1]) to recruit the target protein to the VHL E3 ligase to initiate its proteasomal degradation. Targeting SMARCA2 in SMARCA4 deficient tumours induces synthetic lethality in preclinical tumour models.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 15
Hydrogen bond donors 5
Rotatable bonds 16
Topological polar surface area 226.21
Molecular weight 943.21
XLogP 4.85
No. Lipinski's rules broken 3
SMILES / InChI / InChIKey
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Canonical SMILES C[C@@H](C1=CC=C(C=C1)C2=C(C)N=CS2)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)[C@H]4CC[C@@H](CC4)CN5CC6(CCC(CC6)N7C=C(C=N7)C8=C(N)N=NC(=C8)C9=C(C=CC=C9)O)C5)O
Isomeric SMILES NC1=C(C2=CN(C3CCC4(CN(C[C@H]5CC[C@@H](CC5)C(N[C@@H](C(C)(C)C)C(N6[C@H](C(N[C@@H](C)C7=CC=C(C8=C(C)N=CS8)C=C7)=O)C[C@@H](O)C6)=O)=O)C4)CC3)N=C2)C=C(C9=C(O)C=CC=C9)N=N1
InChI InChI=1S/C52H66N10O5S/c1-31(34-14-16-35(17-15-34)45-32(2)54-30-68-45)56-49(66)43-22-39(63)27-61(43)50(67)46(51(3,4)5)57-48(65)36-12-10-33(11-13-36)25-60-28-52(29-60)20-18-38(19-21-52)62-26-37(24-55-62)41-23-42(58-59-47(41)53)40-8-6-7-9-44(40)64/h6-9,14-17,23-24,26,30-31,33,36,38-39,43,46,63-64H,10-13,18-22,25,27-29H2,1-5H3,(H2,53,59)(H,56,66)(H,57,65)/t31-,33-,36-,39+,43-,46+/m0/s1
InChI Key GMCWCUOAGNWNLO-YTZIVEPUSA-N
References
1. Yang L, Tu W, Huang L, Miao B, Kaneshige A, Jiang W, Leng L, Wang M, Wen B, Sun D et al.. (2023)
Discovery of SMD-3040 as a Potent and Selective SMARCA2 PROTAC Degrader with Strong in vivo Antitumor Activity.
J Med Chem, 66 (15): 10761-10781. [PMID:37523716]