SIM1   Click here for help

GtoPdb Ligand ID: 11777

Synonyms: compound 3 [PMID: 34675414]
Compound class: Synthetic organic
Comment: SIM1 is a first-in-class trivalent PROTAC molecule [1]. It contains two bromo and extra terminal (BET) domain inhibitor ligand components and a von Hippel-Lindau (VHL) ligand domain which are tethered together by a branched linker. This approach increases the valency for target protein binding compared to earlier generation bivalent PROTAC molecules. SIM1 acts as a low picomolar BET degrader in vitro, and has favourable in vivo pharmacokinetics. BET inhibitors are being explored for anticancer activity.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 25
Hydrogen bond donors 5
Rotatable bonds 44
Topological polar surface area 404.26
Molecular weight 1616.6
XLogP 9.47
No. Lipinski's rules broken 3
SMILES / InChI / InChIKey
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Canonical SMILES Clc1ccc(cc1)C1=N[C@@H](CC(=O)NCCOCCOCCOCC(COCC(=O)N[C@@H](C(C)(C)C)C(=O)N2C[C@@H](C[C@H]2C(=O)NCc2ccc(cc2)c2scnc2C)O)(COCCOCCOCCNC(=O)C[C@@H]2N=C(c3ccc(cc3)Cl)c3c(n4c2nnc4C)sc(c3C)C)C)c2n(c3c1c(C)c(s3)C)c(nn2)C
Isomeric SMILES O[C@@H]1C[C@H](N(C1)C(=O)[C@H](C(C)(C)C)NC(=O)COCC(COCCOCCOCCNC(=O)C[C@H]1c2n(c3c(C(=N1)c1ccc(cc1)Cl)c(c(s3)C)C)c(nn2)C)(COCCOCCOCCNC(=O)C[C@H]1c2n(c3c(C(=N1)c1ccc(cc1)Cl)c(c(s3)C)C)c(nn2)C)C)C(=O)NCc1ccc(cc1)c1c(ncs1)C
InChI InChI=1S/C79H98Cl2N14O13S3/c1-46-49(4)110-76-66(46)68(54-16-20-57(80)21-17-54)86-60(72-91-89-51(6)94(72)76)37-63(97)82-24-26-102-28-30-104-32-34-106-42-79(11,44-108-41-65(99)88-71(78(8,9)10)75(101)93-40-59(96)36-62(93)74(100)84-39-53-12-14-56(15-13-53)70-48(3)85-45-109-70)43-107-35-33-105-31-29-103-27-25-83-64(98)38-61-73-92-90-52(7)95(73)77-67(47(2)50(5)111-77)69(87-61)55-18-22-58(81)23-19-55/h12-23,45,59-62,71,96H,24-44H2,1-11H3,(H,82,97)(H,83,98)(H,84,100)(H,88,99)/t59-,60+,61+,62+,71-/m1/s1
InChI Key RARNTROXRCXFHV-CMRSQZKGSA-N
Classification Click here for help
Compound class Synthetic organic
Ligand families/groups PROTACs, molecular glues and other degraders
IUPAC Name Click here for help
N,N'-(11-((2-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)- 3,3-dimethyl-1-oxobutan-2-yl)amino)-2-oxoethoxy)methyl)-11-methyl-3,6,9,13,16,19- hexaoxahenicosane-1,21-diyl)bis(2-((S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2- f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetamide)
Synonyms Click here for help
compound 3 [PMID: 34675414]
Database Links Click here for help
GtoPdb PubChem SID 458923812
PubChem CID 156022820
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