uproleselan   Click here for help

GtoPdb Ligand ID: 11995

Synonyms: ABI-701 | ABI701 | GMI-1271 | GMI1271
Compound class: Synthetic organic
Comment: Uproleselan (GMI-1271) is a selective, glycomimetic, selectin E antagonist [1]. It prevents leukocyte adhesion to endothelial cells. Uproleselan disrupts leukocyte-mediated endothelial damage [6], a mechanism that has been examined for potential to combat venous thrombosis [3,5]. It is also under investigation for use in cancer as selectin E is involved in cancer cell trafficking [4]. In the tumour microenvironment uproleselan disrupts extravasation and adhesion which are crucial components that contribute to metastasis.

COVID-19: Selectin E is a biomarker for acute respiratory distress syndrome (ARDS), that has pro-inflammatory actions that enhance cytokine release and promote continued influx of neutrophils. This existing evidence had led to inclusion of uproleselan in a clinical trial that is designed to determine if antagonising selectin E can aid recovery in patients with severe COVID-19 pneumonia/ARDS.
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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
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 30
Hydrogen bond donors 9
Rotatable bonds 55
Topological polar surface area 382.66
Molecular weight 1303.72
XLogP -2.09
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
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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 COCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)NCCNC(=O)[C@@H]1C[C@H](CC)[C@H]([C@@H](C1)O[C@@H]1O[C@H](CO)[C@@H]([C@@H]([C@H]1NC(=O)C)O[C@H](C(=O)O)CC1CCCCC1)O)O[C@@H]1O[C@@H](C)[C@H]([C@H]([C@@H]1O)O)O
Isomeric SMILES CC[C@H]1C[C@H](C[C@H]([C@@H]1O[C@H]1[C@H]([C@@H]([C@@H]([C@@H](O1)C)O)O)O)O[C@H]1[C@@H]([C@H]([C@H]([C@H](O1)CO)O)O[C@@H](CC1CCCCC1)C(=O)O)NC(=O)C)C(=O)NCCNC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOC
InChI InChI=1S/C60H109N3O27/c1-5-44-38-45(39-46(55(44)90-60-54(70)53(69)51(67)41(2)86-60)88-59-50(63-42(3)65)56(52(68)48(40-64)89-59)87-47(58(72)73)37-43-9-7-6-8-10-43)57(71)62-13-12-61-49(66)11-14-75-17-18-77-21-22-79-25-26-81-29-30-83-33-34-85-36-35-84-32-31-82-28-27-80-24-23-78-20-19-76-16-15-74-4/h41,43-48,50-56,59-60,64,67-70H,5-40H2,1-4H3,(H,61,66)(H,62,71)(H,63,65)(H,72,73)/t41-,44-,45+,46+,47-,48+,50+,51+,52-,53+,54-,55+,56+,59+,60-/m0/s1
InChI Key LYSYOXNOOPBOSC-NGSKMYNLSA-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. Culmer DL, Dunbar ML, Hawley AE, Sood S, Sigler RE, Henke PK, Wakefield TW, Magnani JL, Myers Jr DD. (2017)
E-selectin inhibition with GMI-1271 decreases venous thrombosis without profoundly affecting tail vein bleeding in a mouse model.
Thromb Haemost, 117 (6): 1171-1181. [PMID:28300869]
2. DeAngelo DJ, Jonas BA, Liesveld JL, Bixby DL, Advani AS, Marlton P, Magnani JL, Thackray HM, Feldman EJ, O'Dwyer ME et al.. (2022)
Phase 1/2 study of uproleselan added to chemotherapy in patients with relapsed or refractory acute myeloid leukemia.
Blood, 139 (8): 1135-1146. [PMID:34543383]
3. Devata S, Angelini DE, Blackburn S, Hawley A, Myers DD, Schaefer JK, Hemmer M, Magnani JL, Thackray HM, Wakefield TW et al.. (2020)
Use of GMI-1271, an E-selectin antagonist, in healthy subjects and in 2 patients with calf vein thrombosis.
Res Pract Thromb Haemost, 4 (2): 193-204. [PMID:32110749]
4. Muz B, Abdelghafer A, Markovic M, Yavner J, Melam A, Salama NN, Azab AK. (2021)
Targeting E-selectin to Tackle Cancer Using Uproleselan.
Cancers (Basel), 13 (2): 335. [PMID:33477563]
5. Myers Jr D, Lester P, Adili R, Hawley A, Durham L, Dunivant V, Reynolds G, Crego K, Zimmerman Z, Sood S et al.. (2020)
A new way to treat proximal deep venous thrombosis using E-selectin inhibition.
J Vasc Surg Venous Lymphat Disord, 8 (2): 268-278. [PMID:32067728]
6. Natoni A, Smith TAG, Keane N, McEllistrim C, Connolly C, Jha A, Andrulis M, Ellert E, Raab MS, Glavey SV et al.. (2017)
E-selectin ligands recognised by HECA452 induce drug resistance in myeloma, which is overcome by the E-selectin antagonist, GMI-1271.
Leukemia, 31 (12): 2642-2651. [PMID:28439107]