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bezisterim   Click here for help

GtoPdb Ligand ID: 13988

Synonyms: 17-ethynyl-5-androstene-3,7,17-triol | HE-3286 | HE3286 | NE-3107 | NE3107
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Bezisterim (NE3107 and formerly HE3286) is a synthetic, orally bioavailable analogue of the adrenal sterol metabolite androstenetriol. It can cross the blood-brain barrier. It has proposed anti-inflammatory and insulin-sensitising activities, which may be beneficial in treating the pathophysiology or symptom development in degenerative brain diseases such as Parkinson's and Alzheimer's, which are associated with chronic low-grade inflammation. The molecular target(s) of bezisterim are not fully resolved. Its anti-inflammatory and insulin-sensitising biological activities likely include modulation of pathways and networks that involve LDL receptor related protein 1 (Lrp1), Mapk3 (ERK1) and Mapk1 (ERK2) [8].
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 3
Hydrogen bond donors 3
Rotatable bonds 0
Topological polar surface area 60.69
Molecular weight 330.46
XLogP 2.06
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 C#C[C@@]1(CC[C@H]2[C@H]3[C@H](CC[C@@]21C)[C@@]4(C)CC[C@@H](CC4=C[C@@H]3O)O)O
Isomeric SMILES C[C@]12CC[C@@H](CC1=C[C@@H]([C@@H]3[C@@H]2CC[C@]4([C@H]3CC[C@]4(C#C)O)C)O)O
InChI InChI=1S/C21H30O3/c1-4-21(24)10-7-16-18-15(6-9-20(16,21)3)19(2)8-5-14(22)11-13(19)12-17(18)23/h1,12,14-18,22-24H,5-11H2,2-3H3/t14-,15-,16-,17-,18+,19-,20-,21-/m0/s1
InChI Key JJKOQZHWYLMASZ-FJWDNACWSA-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. Ahlem C, Auci D, Mangano K, Reading C, Frincke J, Stickney D, Nicoletti F. (2009)
HE3286: a novel synthetic steroid as an oral treatment for autoimmune disease.
Ann N Y Acad Sci, 1173: 781-90. [PMID:19758229]
2. Auci D, Kaler L, Subramanian S, Huang Y, Frincke J, Reading C, Offner H. (2007)
A new orally bioavailable synthetic androstene inhibits collagen-induced arthritis in the mouse: androstene hormones as regulators of regulatory T cells.
Ann N Y Acad Sci, 1110: 630-40. [PMID:17911478]
3. Conrad D, Wang A, Pieters R, Nicoletti F, Mangano K, van Heeckeren AM, White SK, Frincke JM, Reading CL, Stickney D et al.. (2010)
HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression.
J Inflamm (Lond), 7: 52. [PMID:21034489]
4. Haroon J, Jordan K, Mahdavi K, Rindner E, Becerra S, Surya JR, Zielinski M, Venkatraman V, Goodenowe D, Hofmeister K et al.. (2024)
A phase 2, open-label study of anti-inflammatory NE3107 in patients with dementias.
Medicine (Baltimore), 103 (30): e39027. [PMID:39058809]
5. Kosiewicz MM, Auci DL, Fagone P, Mangano K, Caponnetto S, Tucker CF, Azeem N, White SK, Frincke JM, Reading CL et al.. (2011)
HE3286, an orally bioavailable synthetic analogue of an active DHEA metabolite suppresses spontaneous autoimmune diabetes in the non-obese diabetic (NOD) mouse.
Eur J Pharmacol, 658 (2-3): 257-62. [PMID:21371458]
6. Offner H, Firestein GS, Boyle DL, Pieters R, Frincke JM, Garsd A, White SK, Reading CL, Auci DL. (2009)
An orally bioavailable synthetic analog of an active dehydroepiandrosterone metabolite reduces established disease in rodent models of rheumatoid arthritis.
J Pharmacol Exp Ther, 329 (3): 1100-9. [PMID:19297421]
7. Reading CL, Ahlem CN, Murphy MF. (2021)
NM101 Phase III study of NE3107 in Alzheimer's disease: rationale, design and therapeutic modulation of neuroinflammation and insulin resistance.
Neurodegener Dis Manag, 11 (4): 289-298. [PMID:34251287]
8. Reading CL, Frincke JM, White SK. (2012)
Molecular targets for 17α-ethynyl-5-androstene-3β,7β,17β-triol, an anti-inflammatory agent derived from the human metabolome.
PLoS One, 7 (2): e32147. [PMID:22384159]
9. Reading CL, Yan J, Testa MA, Simonson DC, Javaid H, Schmunk L, Martin-Herranz DE, Brooke R, Gordevicius J, Zhang J et al.. (2025)
An exploratory analysis of bezisterim treatment associated with decreased biological age acceleration, and improved clinical measure and biomarker changes in mild-to-moderate probable Alzheimer's disease.
Front Neurosci, 19: 1516746. [PMID:40386807]