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etavopivat   Click here for help

GtoPdb Ligand ID: 11975

Synonyms: FT-4202 | FT4202
Compound class: Synthetic organic
Comment: Etavopivat (FT-4202) is an orally active, small molecule allosteric activator of the pyruvate kinase (PK) isoform that's found in erythrocytes (PK-R) [5]. It activates the erythrocytic glycolytic pathway [2-3]. Etavopivat is similar in function to mitapivat.
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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.

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View interactive charts of activity data across species

etavopivat is commercially available from our sponsors

2D Structure
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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.

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Physico-chemical Properties
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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.

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Hydrogen bond acceptors 7
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 117.65
Molecular weight 457.13
XLogP -0.58
No. Lipinski's rules broken 0

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
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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/)

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Canonical SMILES OC[C@@H](C(=O)N1CC2=C(C1)CN(C2)S(=O)(=O)c1cnc2c(c1)OCCO2)c1ccccc1
Isomeric SMILES C1COc2c(O1)cc(cn2)S(=O)(=O)N1CC2=C(C1)CN(C2)C(=O)[C@H](CO)c1ccccc1
InChI InChI=1S/C22H23N3O6S/c26-14-19(15-4-2-1-3-5-15)22(27)24-10-16-12-25(13-17(16)11-24)32(28,29)18-8-20-21(23-9-18)31-7-6-30-20/h1-5,8-9,19,26H,6-7,10-14H2/t19-/m1/s1
InChI Key KZFFYEPYCVDOGE-LJQANCHMSA-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. Forsyth S, Schroeder P, Geib J, Vrishabhendra L, Konstantinidis DG, LaSalvia K, Ribadeneira MD, Wu E, Kelly P, Kalfa TA. (2022)
Safety, Pharmacokinetics, and Pharmacodynamics of Etavopivat (FT-4202), an Allosteric Activator of Pyruvate Kinase-R, in Healthy Adults: A Randomized, Placebo-Controlled, Double-Blind, First-in-Human Phase 1 Trial.
Clin Pharmacol Drug Dev, 11 (5): 654-665. [PMID:35019238]
2. Kuo KHM. (2023)
Pyruvate kinase activators: targeting red cell metabolism in thalassemia.
Hematology Am Soc Hematol Educ Program, 2023 (1): 114-120. [PMID:38066911]
3. Matte A, Federti E, De Franceschi L. (2023)
Erythrocyte pyruvate kinase activation in red cell disorders.
Curr Opin Hematol, 30 (3): 93-98. [PMID:36853806]
4. Saraf SL, Hagar R, Idowu M, Osunkwo I, Cruz K, Kuypers FA, Brown RC, Geib J, Ribadeneira M, Schroeder P et al.. (2024)
Multicenter, phase 1 study of etavopivat (FT-4202) treatment for up to 12 weeks in patients with sickle cell disease.
Blood Adv, 8 (16): 4459-4475. [PMID:38640200]
5. Schroeder P, Fulzele K, Forsyth S, Ribadeneira MD, Guichard S, Wilker E, Marshall CG, Drake A, Fessler R, Konstantinidis DG et al.. (2022)
Etavopivat, a Pyruvate Kinase Activator in Red Blood Cells, for the Treatment of Sickle Cell Disease.
J Pharmacol Exp Ther, 380 (3): 210-219. [PMID:35031585]