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.
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species

SIM1 is commercially available from our sponsors

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 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

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 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

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/)

For advanced searching click here to open chemical structure editor

Similar Ligands Click here for help
YX862
Click here for ligand page
KT-333
Click here for ligand page
Targets
signal transducer and activator of transcription 3
MS8709
Click here for ligand page
Targets
euchromatic histone lysine methyltransferase 1; euchromatic histone lysine methyltransferase 2
lirodegimod
Click here for ligand page
Targets
signal transducer and activator of transcription 3
SOS1 PROTAC 23
Click here for ligand page
WD6305
Click here for ligand page
Targets
methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit
MS132
Click here for ligand page
Targets
WD repeat domain 5
SGI-1776-VHL-02
Click here for ligand page
PIM447-VHL-01
Click here for ligand page
SMD-3040
Click here for ligand page
Targets
SWI/SNF related BAF chromatin remodeling complex subunit ATPase 2; SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4
compound 11 [PMID: 37449845]
Click here for ligand page
Targets
transglutaminase 2
CoV Mpro VHL PROTAC 9 [US11518759]
Click here for ligand page
Targets
CoV 3C-like (main) protease
A947
Click here for ligand page
Targets
SWI/SNF related BAF chromatin remodeling complex subunit ATPase 2; SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4
NAMPT PROTAC B4
Click here for ligand page
MS15
Click here for ligand page
Targets
AKT serine/threonine kinase 1; AKT serine/threonine kinase 2; AKT serine/threonine kinase 3
C004019
Click here for ligand page
MS8815
Click here for ligand page
Targets
von Hippel-Lindau tumor suppressor
SOS1 PROTAC 9d
Click here for ligand page
Targets
SOS Ras/Rac guanine nucleotide exchange factor 1
XL01126
Click here for ligand page
Targets
leucine rich repeat kinase 2
AZ14117230
Click here for ligand page
Targets
embryonic ectoderm development
DT2216
Click here for ligand page
TBK1 PROTAC 3i
Click here for ligand page
Targets
TANK binding kinase 1
MZ1
Click here for ligand page
Targets
bromodomain containing 4
PROTAC 3
Click here for ligand page
MS39
Click here for ligand page
Targets
epidermal growth factor receptor
compound 3 [PMID: 31804822]
Click here for ligand page
Targets
mitogen-activated protein kinase kinase 1
ARD-266
Click here for ligand page
Targets
Androgen receptor
ERD-308
Click here for ligand page
Targets
Estrogen receptor-α
ARV-771
Click here for ligand page
Targets
bromodomain containing 2; bromodomain containing 3; bromodomain containing 4
MS432
Click here for ligand page
Targets
mitogen-activated protein kinase kinase 1; mitogen-activated protein kinase kinase 2
dTRIM24
Click here for ligand page
Targets
tripartite motif containing 24
SIAIS178
Click here for ligand page
Targets
ABL proto-oncogene 1, non-receptor tyrosine kinase
ARD-69
Click here for ligand page
Targets
Androgen receptor