A947   Click here for help

GtoPdb Ligand ID: 12308

Compound class: Synthetic organic
Comment: A947 is a selective degrader of SMARCA2 [1]. It is a PROTAC class molecule that targets SMARCA2 protein for degradation via ligation with the VHL E3 ubiquitin ligase. Its target protein binding component interacts with the bromodomains of SMARCA2 and -4 and the 5th bromodomain of polybromo 1 (PBRM1). A947 was developed by Arvinas/Genentech to assess the utility of targeting SMARCA2 in SMARCA4-mutated cancers that become dependent on the SMARCA2 paralog for survival.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 15
Hydrogen bond donors 4
Rotatable bonds 19
Topological polar surface area 253.14
Molecular weight 1120.57
XLogP 8.76
No. Lipinski's rules broken 3
SMILES / InChI / InChIKey
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Canonical SMILES O[C@H]1CN([C@@H](C1)C(=O)N[C@H](c1ccc(cc1)c1scnc1C)C)C(=O)[C@@H](c1onc(c1)N1CCC(CC1)CN1CCC(CC1)OC1CC(C1)Oc1nccc(c1)N1C2CCC1CN(C2)c1cc(nnc1N)c1ccccc1O)C(C)C
Isomeric SMILES Cc1c(scn1)c1ccc(cc1)[C@H](C)NC(=O)[C@@H]1C[C@H](CN1C(=O)[C@@H](c1cc(no1)N1CCC(CC1)CN1CCC(CC1)OC1CC(C1)Oc1nccc(c1)N1C2CCC1CN(C2)c1cc(nnc1N)c1ccccc1O)C(C)C)O
InChI InChI=1S/C61H76N12O7S/c1-36(2)57(61(77)72-34-45(74)26-52(72)60(76)65-37(3)40-9-11-41(12-10-40)58-38(4)64-35-81-58)54-30-55(68-80-54)70-23-16-39(17-24-70)31-69-21-18-46(19-22-69)78-47-27-48(28-47)79-56-25-42(15-20-63-56)73-43-13-14-44(73)33-71(32-43)51-29-50(66-67-59(51)62)49-7-5-6-8-53(49)75/h5-12,15,20,25,29-30,35-37,39,43-48,52,57,74-75H,13-14,16-19,21-24,26-28,31-34H2,1-4H3,(H2,62,67)(H,65,76)/t37-,43?,44?,45+,47?,48?,52-,57+/m0/s1
InChI Key QQVCUSPUMMUFTD-NCXNEFEISA-N
References
1. Cantley J, Ye X, Rousseau E, Januario T, Hamman BD, Rose CM, Cheung TK, Hinkle T, Soto L, Quinn C et al.. (2022)
Selective PROTAC-mediated degradation of SMARCA2 is efficacious in SMARCA4 mutant cancers.
Nat Commun, 13 (1): 6814. [PMID:36357397]