LY3154207   Click here for help

GtoPdb Ligand ID: 10506

Synonyms: compound 3 [PMID: 31532644] | LY-3154207
PDB Ligand
Compound class: Synthetic organic
Comment: LY3154207 is a potent, selective and orally active dopamine D1 receptor positive allosteric modulator (PAM) [1]. The allosteric binding site of LY3154207 has been determined to reside at the intracellular loop 2 (ICL2) region of the receptor.
D1 PAMs are being developed to address the poor drug-like properties of selective orthosteric D1 agonists. In particular, LY3154207 does not induce tachyphylaxis in preclinical models, whereas orthosteric agonists do. LY3154207 exhibits pro-cognitive and motor-enhancing effects in vivo, and is being considered for potential utility in the treatment of neuropsychiatric disorders [2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 60.77
Molecular weight 449.15
XLogP 4.62
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES OCC1Cc2c(cccc2C(N1C(=O)Cc1c(Cl)cccc1Cl)C)CCC(O)(C)C
Isomeric SMILES OC[C@H]1Cc2c(cccc2[C@@H](N1C(=O)Cc1c(Cl)cccc1Cl)C)CCC(O)(C)C
InChI InChI=1S/C24H29Cl2NO3/c1-15-18-7-4-6-16(10-11-24(2,3)30)19(18)12-17(14-28)27(15)23(29)13-20-21(25)8-5-9-22(20)26/h4-9,15,17,28,30H,10-14H2,1-3H3/t15-,17+/m0/s1
InChI Key XHCSBQBBGNQINS-DOTOQJQBSA-N
Bioactivity Comments
LY3154207 produces minimal agonist activity [1]. In vivo experiments using LY3154207 were carried out in mice engineered to express the human D1 receptor because of the difference in potency that was determined between the human and mouse D1 receptors for LY3154207. The in vitro EC50 potentiator potency of LY3154207 for the human D5 receptor was determined to be >10 μM [1].
Selectivity at GPCRs
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
D1 receptor Primary target of this compound Hs Allosteric modulator Positive 8.6 pEC50 - 1
pEC50 8.6 (EC50 2.3x10-9 M) [1]
Description: Potentiator potency: Increase of cAMP by LY3154207 in the presence of an EC20 concentration of dopamine in HEK293 cells transiently expressing human D1 receptors.
D1 receptor Mm Allosteric modulator Positive 7.2 pEC50 - 1
pEC50 7.2 (EC50 6.2x10-8 M) [1]
Description: Potentiator potency: Increase of cAMP by LY3154207 in the presence of an EC20 concentration of dopamine in HEK293 cells transiently expressing mouse D1 receptors.