obicetrapib   Click here for help

GtoPdb Ligand ID: 12205

Synonyms: AMG-899 | DEZ-001 | TA-8995 | TA8995
Compound class: Synthetic organic
Comment: Obicetrapib is a clinical lead, orally bioavailable, small molecule, cholesterol ester transfer protein (CETP; P11597) inhibitor [1]. It was developed as a treament for dyslipidemia. Agents of the CETP inhibitor class are proposed to increase HDL cholesterol, lower LDL cholesterol, and enhance reverse cholesterol transport, as a mechanism to reduce the risks of elevated cholesterol on atherosclerosis. Prior to the re-launching of trials involving obicetrapib by NewAmsterdam Pharma, no CETP inhibitor had demonstrated sufficient safety and/or efficacy in a clinical study to warrant continued development [2].

obicetrapib 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 8
Hydrogen bond donors 1
Rotatable bonds 16
Topological polar surface area 105.09
Molecular weight 722.22
XLogP 7.73
No. Lipinski's rules broken 2

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 CCOC(=O)N1[C@H](CC)C[C@@H](c2c1ccc(c2)C(F)(F)F)N(c1ncc(cn1)OCCCC(=O)O)Cc1cc(cc(c1)C(F)(F)F)C(F)(F)F
Isomeric SMILES CC[C@@H]1C[C@@H](c2c(N1C(=O)OCC)ccc(c2)C(F)(F)F)N(Cc1cc(cc(c1)C(F)(F)F)C(F)(F)F)c1ncc(cn1)OCCCC(=O)O
InChI InChI=1S/C32H31F9N4O5/c1-3-22-14-26(24-13-19(30(33,34)35)7-8-25(24)45(22)29(48)49-4-2)44(28-42-15-23(16-43-28)50-9-5-6-27(46)47)17-18-10-20(31(36,37)38)12-21(11-18)32(39,40)41/h7-8,10-13,15-16,22,26H,3-6,9,14,17H2,1-2H3,(H,46,47)/t22-,26+/m1/s1
InChI Key NRWORBQAOQVYBJ-GJZUVCINSA-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/)
References
1. Ford J, Lawson M, Fowler D, Maruyama N, Mito S, Tomiyasu K, Kinoshita S, Suzuki C, Kawaguchi A, Round P et al.. (2014)
Tolerability, pharmacokinetics and pharmacodynamics of TA-8995, a selective cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects.
Br J Clin Pharmacol, 78 (3): 498-508. [PMID:24628035]
2. Nicholls SJ, Nelson AJ, Kastelein JJP, Ditmarsch M, Hsieh A, Johnson J, Curcio D, Kling D, Kirkpatrick CF, Davidson MH. (2024)
Obicetrapib exhibits favorable physiochemical and pharmacokinetic properties compared to previous cholesteryl ester transfer protein inhibitors: An integrated summary of results from non-human primate studies and clinical trials.
Pharmacol Res Perspect, 12 (6): e70010. [PMID:39425271]