KHELLIN

US Previously Marketed

First approved in 1950

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H12O5
Molecular Weight	260.2421
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C2OC(C)=CC(=O)C2=C(OC)C3=C1OC=C3

InChI

InChIKey=HSMPDPBYAYSOBC-UHFFFAOYSA-N

InChI=1S/C14H12O5/c1-7-6-9(15)10-11(16-2)8-4-5-18-12(8)14(17-3)13(10)19-7/h4-6H,1-3H3

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/npp/khella.html | Krutmann, J. et al. (2008) Dermatological Phototherapy and Photodiagnostic Methods, page 168, retrieved from: https://books.google.ru/books?id=Z35aWU5TAWoC | https://www.ncbi.nlm.nih.gov/pubmed/14888509

Khellin is a crystalline extract of a crude drug, which has long been used in Egypt for the treatment of ureteral colic. It is used in the management of bronchial asthma and angina pectoris. Interest in khellin as an adjunct to ultraviolet (UV) light therapy in the treatment of vitiligo is based on the structural similarity between khellin and the psoralens. Success has been reported using oral and topical khellin in clinical studies but it is not likely that khellin will be approved for the treatment of vitiligo. Unwanted side effects of khellin include dizziness, reversible cholestatic jaundice, pseudoallergic reaction, and elevated levels of liver enzymes (transaminases and gamma-glutamyltransferase).

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytochrome P450 1A1 31 Target ID: CHEMBL2231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24069365	Inhibitor 8228
Aryl hydrocarbon receptor 26 Target ID: CHEMBL3201 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24069365	Activator 1410
Target ID: Calcium influx Sources: https://www.ncbi.nlm.nih.gov/pubmed/2568462	Inhibitor 8228

Conditions

Condition	Modality	Highest Phase	Product
Vitiligo 9 Sources: https://www.drugs.com/npp/khella.html http://emjreviews.com/blog/khellin-vitiligo-treatment/	Primary	Phase II 1144	Ammivin Approved Use Khellin is used for Angina pectoris, Asthma, Vitiligo, Ultraviolet irradiation and other conditions.
Angina pectoris 94 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6421255 http://en.pharmacodia.com/web/drug/1_22584.html https://www.drugs.com/npp/khella.html	Palliative	Approved 8360	Ammivin Approved Use Khellin is used for Angina pectoris, Asthma, Vitiligo, Ultraviolet irradiation and other conditions.
Asthma 237 Sources: https://www.drugs.com/npp/khella.html https://www.ncbi.nlm.nih.gov/pubmed/14868371	Palliative	Approved 8360	Ammivin Approved Use Khellin is used for Angina pectoris, Asthma, Vitiligo, Ultraviolet irradiation and other conditions.

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1579	inhibitor 1752	inhibitor 1837

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A1 110 CYP1B1 19 CYP1A2 1509 CYP2C19 1463 OATP1B1 781 OATP1B3 700		CYP1A1 109

Drug as perpetrator

Target	Modality	Activity
CYP2C19 1537	inhibitor 3240 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083783/, https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ0NzQ2In19	no [IC50 >10 uM]
CYP2C9 1803	inhibitor 3240 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083783/	no [IC50 >10 uM]
CYP2D6 1875	inhibitor 3240 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083783/	no [IC50 >10 uM]
CYP3A4 1909	inhibitor 3240 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083783/, https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNDQ3NDYifX0%3D	no [IC50 >10 uM]
CYP1B1 68	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/31458985/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083783/	weak [IC50 34.6 uM]
CYP1A2 1673	inhibitor 3240 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083783/, https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ0NzQ2In19	yes [IC50 0.04 uM]
CYP1A1 218	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/31458985/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083783/	yes [IC50 4.02 uM]
OATP1B1 796	inhibitor 3240 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ0NzQ2In19	yes [Inhibition 10 uM]
OATP1B3 709	inhibitor 3240 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ0NzQ2In19	yes [Inhibition 10 uM]
CYP1A1 218	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/24069365/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6133	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6133
ChemicalBook	CB5269554	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5269554
MolPort	MolPort-000-724-273	https://www.molport.com/shop/molecule-link/MolPort-000-724-273
ZINC	ZINC000000056654	http://zinc15.docking.org/substances/ZINC000000056654
eMolecules	524621	https://www.emolecules.com/cgi-bin/more?vid=524621

PubMed

Title	Date	PubMed
Cytosolic acidification as a signal mediating hyperosmotic stress responses in Dictyostelium discoideum.	2001	11415467
Evaluation of the process for superoxide production by NADPH oxidase in human neutrophils: evidence for cytoplasmic origin of superoxide.	2001	11333112
Coronin from roots of Annona muricata, a putative intermediate in acetogenin biosynthesis (1).	2001 Aug	11509986
Genetic approaches to dissect the mechanisms of two distinct pathways of cell cycle-coupled cytokinesis in Dictyostelium.	2001 Dec	11942613
Coronin forms a stable dimer through its C-terminal coiled coil region: an implicated role in its localization to cell periphery.	2001 Mar	11260266
Role of actin polymerization and actin cables in actin-patch movement in Schizosaccharomyces pombe.	2001 Mar	11231572
An SH2-domain-containing kinase negatively regulates the phosphatidylinositol-3 kinase pathway.	2001 Mar 15	11274054
Long-term results in the treatment of vitiligo with oral khellin plus UVA.	2001 May-Jun	11358729
Membrane-cytoskeleton interactions during the formation of the immunological synapse and subsequent T-cell activation.	2002 Nov	12445270
Immune evasion by Mycobacterium tuberculosis: living with the enemy.	2003 Aug	12900278
KUVA (khellin plus ultraviolet A) stimulates proliferation and melanogenesis in normal human melanocytes and melanoma cells in vitro.	2003 Oct	14616361
Vitamin D3-dependent pathway regulates TACO gene transcription.	2003 Oct 24	14550285
The chemical investigations on the ripe fruits of Ammi visnaga (Lam.) Lamarck growing in Turkey.	2004 Apr	14984092
Coronin-1 expression in T lymphocytes: insights into protein function during T cell development and activation.	2004 Feb	14734608
Cytotoxic activity of five compounds isolated from Colombian plants.	2004 Mar	15030931
Cholesterol-sensor initiates M. tuberculosis entry into human macrophages.	2004 Mar	15030187
Treatment of vitiligo with local khellin and UVA: comparison with systemic PUVA.	2004 Mar	14987278
Conformational changes in the Arp2/3 complex leading to actin nucleation.	2005 Jan	15592479
Dynamic properties of Legionella-containing phagosomes in Dictyostelium amoebae.	2005 Jul	15953031
A single-nucleotide polymorphism in the gene encoding lymphoid protein tyrosine phosphatase (PTPN22) confers susceptibility to generalised vitiligo.	2005 Oct	16015369
Phosphorylation of coronin 1B by protein kinase C regulates interaction with Arp2/3 and cell motility.	2005 Sep 9	16027158
Green tea polyphenol inhibits Mycobacterium tuberculosis survival within human macrophages.	2006	16352457
Effusion and solid lymphomas have distinctive gene and protein expression profiles in an animal model of primary effusion lymphoma.	2006 Aug	16741895
Requirement for coronin 1 in T lymphocyte trafficking and cellular homeostasis.	2006 Aug 11	16902139
Transcriptional regulation of artemin is related to neurite outgrowth and actin polymerization in mature DRG neurons.	2006 Aug 14	16781061
Time-resolved responses to chemoattractant, characteristic of the front and tail of Dictyostelium cells.	2006 Dec 11	17126332
The identification of a new actin-binding region in p57.	2006 Jan	16467882
The crystal structure of murine coronin-1: a regulator of actin cytoskeletal dynamics in lymphocytes.	2006 Jan	16407068
Ultraviolet photoionization of the photosensitizers khellin and visnagin in aqueous solution and in micelles: one-photon ionization is a minor process.	2006 Mar	16520866
Microtubules regulate disassembly of epithelial apical junctions.	2006 Mar 1	16509970
The embryonic muscle transcriptome of Caenorhabditis elegans.	2007	17848203
Global gene expression analysis and regulation of the principal genes expressed in bovine placenta in relation to the transcription factor AP-2 family.	2007 Apr 27	17462098
Survival of mycobacteria in macrophages is mediated by coronin 1-dependent activation of calcineurin.	2007 Jul 13	17632055
Epithelial grafting for vitiligo requires ultraviolet A phototherapy to increase success rate.	2007 Jun	17524129
Coronin function is required for chemotaxis and phagocytosis in human neutrophils.	2007 May 1	17442961
STATc is a key regulator of the transcriptional response to hyperosmotic shock.	2007 May 21	17517120
Gene expression profiles in testis of pigs with extreme high and low levels of androstenone.	2007 Nov 7	17988377
Functional analysis of cancer-associated EGFR mutants using a cellular assay with YFP-tagged EGFR intracellular domain.	2007 Sep 18	17877814
Coronin-1A stabilizes F-actin by bridging adjacent actin protomers and stapling opposite strands of the actin filament.	2008 Feb 22	18177666
The lupus-related Lmb3 locus contains a disease-suppressing Coronin-1A gene mutation.	2008 Jan	18199416
Coronin-1A epigenomics governs mycobacterial persistence in tuberculosis.	2008 Jan	18031535

Patents

Sample Use Guides

In Vivo Use Guide

Oral: 200 mg/day Topical: as a 2% preparation

Route of Administration: Other

In Vitro Use Guide

In neutral O2-saturated aqueous solution, the photosensitized His degradation quantum yield is about 8x10(-5) for khellin. In O2-saturated aqueous solution, khellin photosensitized the oxidation of Trp with a quantum yield of 1.5x10(-4), which is quite low.

Name

Type

Language

KHELLIN

Official Name

English

NSC-37744

Code

English

khellin [INN]

Common Name

English

KHELLIN [MI]

Common Name

English

Khellin [WHO-DD]

Common Name

English

4,9-DIMETHOXY-7-METHYL-5H-FURO(3,2-G)(1)BENZOPYRAN-5-ONE

Systematic Name

English

VISCARDAN

Brand Name

English

KHELLIN [MART.]

Common Name

English

NSC-25509

Code

English

4,9-DIMETHOXY-7-METHYL-5-OXOFURO(3,2-G)-1,2-CHROMENE

Common Name

English

AMMIVIN

Brand Name

English

KHELLOYD

Brand Name

English

CORONIN

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C45597