3β-OH   Click here for help

GtoPdb Ligand ID: 10537

Synonyms: (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile [1] | B260 [2]
Compound class: Synthetic organic
Comment: 3β-OH is a neuroactive steroid analogue that produces general anaesthetic/hypnotic effects in vivo, but without associated neurotoxicity [1]. It blocks presynaptic transmitter release without affecting major postsynaptic ligand-gated ion channels. The chemical structure of 3β-OH is based on that of progesterone, with an OH substitution at position 3, and a CN group substitution at position 3. This chemical structure is claimed as B260 in patent WO2015149066A1 [2]. Mechanistically, 3β-OH selectively targets T-type voltage-gated calcium channels (T-channels; Cav3.1, Cav3.2, and Cav3.3) to mediate its hypnotic activity. 3β-OH exhibits minimal activity towards voltage-gated Na+ and K+ currents, N-type and L-type Ca2+ currents [3-4] or currents generated via recombinant GABAA and NMDA channels [5].
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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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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 2
Hydrogen bond donors 1
Rotatable bonds 0
Topological polar surface area 44.02
Molecular weight 301.24
XLogP 5.94
No. Lipinski's rules broken 1

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 N#CC1CCC2C1(C)CCC1C2CCC2C1(C)CCC(C2)O
Isomeric SMILES N#C[C@H]1CCC2[C@]1(C)CCC1C2CC[C@H]2[C@]1(C)CC[C@@H](C2)O
InChI InChI=1S/C20H31NO/c1-19-9-7-15(22)11-13(19)3-5-16-17-6-4-14(12-21)20(17,2)10-8-18(16)19/h13-18,22H,3-11H2,1-2H3/t13-,14-,15+,16?,17?,18?,19+,20-/m1/s1
InChI Key DVTDUTYENPZLFP-FXEFULGUSA-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. Atluri N, Joksimovic SM, Oklopcic A, Milanovic D, Klawitter J, Eggan P, Krishnan K, Covey DF, Todorovic SM, Jevtovic-Todorovic V. (2018)
A neurosteroid analogue with T-type calcium channel blocking properties is an effective hypnotic, but is not harmful to neonatal rat brain.
Br J Anaesth, 120 (4): 768-778. [PMID:29576117]
2. Jevtovic-Todorovic V, Todorovic S. (2015)
General anesthetics that are not neurotoxic.
Patent number: WO2015149066A1. Assignee: University Of Virginia Patent Foundation. Priority date: 28/03/2014. Publication date: 01/10/2015.
3. Joksovic PM, Covey DF, Todorovic SM. (2007)
Inhibition of T-type calcium current in the reticular thalamic nucleus by a novel neuroactive steroid.
Ann N Y Acad Sci, 1122: 83-94. [PMID:18077566]
4. Todorovic SM, Pathirathna S, Brimelow BC, Jagodic MM, Ko SH, Jiang X, Nilsson KR, Zorumski CF, Covey DF, Jevtovic-Todorovic V. (2004)
5beta-reduced neuroactive steroids are novel voltage-dependent blockers of T-type Ca2+ channels in rat sensory neurons in vitro and potent peripheral analgesics in vivo.
Mol Pharmacol, 66 (5): 1223-35. [PMID:15280444]
5. Wang M, He Y, Eisenman LN, Fields C, Zeng CM, Mathews J, Benz A, Fu T, Zorumski E, Steinbach JH et al.. (2002)
3beta -hydroxypregnane steroids are pregnenolone sulfate-like GABA(A) receptor antagonists.
J Neurosci, 22 (9): 3366-75. [PMID:11978813]