LATRUNCULIN B

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H29NO5S
Molecular Weight	395.513
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]1(CSC(=O)N1)[C@@]2(O)C[C@@]3([H])C[C@@]([H])(CC[C@H](C)C=CCCC(C)=CC(=O)O3)O2

InChI

InChIKey=NSHPHXHGRHSMIK-JRIKCGFMSA-N

InChI=1S/C20H29NO5S/c1-13-5-3-4-6-14(2)9-18(22)25-16-10-15(8-7-13)26-20(24,11-16)17-12-27-19(23)21-17/h3,5,9,13,15-17,24H,4,6-8,10-12H2,1-2H3,(H,21,23)/b5-3-,14-9-/t13-,15-,16-,17+,20-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C20H29NO5S
Molecular Weight	395.513
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25237590 | https://www.ncbi.nlm.nih.gov/pubmed/24179529 | https://www.ncbi.nlm.nih.gov/pubmed/11181185

Latrunculin B originates from Latrunculia (now Negombata) magnifica, a sponge from the Red Sea. Latrunculin B inhibits the assembly of actin microfilaments by 1:1 molecular binding of free actin monomers in the cell cytoplasm. It may be a potential therapeutic agent for glaucoma. Latrunculin B induced destabilization of the actin microfilament and apoptosis in a dose-dependent manner, as demonstrated by morphological changes and nuclear condensation in the PC3M cells. In addition, it resulted in an increase in the levels of gamma-H2AX recruitment, implicating the induction of DNA damage, including double-strand breaks. Induction of Bax, with little effect on Bcl-2 expression, indicated that actin disruption causes apoptosis through activation of Bax signaling in PC3M cells. This data might helps to develop the strategy for actin-based anticancer chemotherapy against highly metastatic prostate cancer.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Actin, cytoplasmic 1 1 Target ID: P60706 Gene ID: 396526.0 Gene Symbol: ACTB Target Organism: Gallus gallus (Chicken) Sources: https://www.ncbi.nlm.nih.gov/pubmed/11181185	Inhibitor 8297		60.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Glaucoma 57 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25237590 http://adisinsight.springer.com/drugs/800021699	Primary	Phase I 428	Unknown Approved Use Unknown
Prostate cancer 178 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24179529	Primary	Basic research	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21399880	Primary	Basic research	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP2 383 MRP4 204 P-gp 1461 MRP1 106 MRP3 157

Drug as perpetrator

Target	Modality	Activity
MRP3 207	inhibitor 3277 Sources: https://core.ac.uk/download/pdf/148288457.pdf#page=120 Page: 130.0	no
MRP4 238	inhibitor 3277 Sources: https://core.ac.uk/download/pdf/148288457.pdf#page=120 Page: 130.0	no
MRP2 475	inhibitor 3277 Sources: https://core.ac.uk/download/pdf/148288457.pdf#page=120 Page: 130.0	weak
MRP1 172	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/21045108/	yes
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17122416/	yes

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific	1814AH	https://aksci.com/item_detail.php?cat=1814AH
Alfa Chemistry	ACM76343947	http://www.alfa-chemistry.com/search.aspx?q=ACM76343947
BOC Sciences	76343-94-7	http://www.bocsci.com/description.asp?cas=76343-94-7
Compound Cloud	56928133
MolPort	MolPort-016-580-840	https://www.molport.com/shop/molecule-link/MolPort-016-580-840
Sigma Aldrich	L5288	http://www.sigmaaldrich.com/catalog/search?term=L5288&interface=All&N=0&mode=match%20partialmax&lang=en®ion=US&focus=product
Tetrahedron	TS80894	http://www.thsci.com/search.do?q=TS80894
Toronto Research Chemicals	L177330	https://www.trc-canada.com/product-detail/?CatNum=L177330

PubMed

Title	Date	PubMed
Targeting protein phosphatase 1 (PP1) to the actin cytoskeleton: the neurabin I/PP1 complex regulates cell morphology.	2002 Jul	12052877
Rho/ROCK pathway contributes to the activation of extracellular signal-regulated kinase/GATA-4 during myocardial cell hypertrophy.	2002 Mar 8	11739382
Rho protein-mediated changes in the structure of the actin cytoskeleton regulate human inducible NO synthase gene expression.	2003 Jul 1	12799187
Modulation of acto-myosin contractility in skeletal muscle myoblasts uncouples growth arrest from differentiation.	2004 Aug 1	15252113
A role for cytoskeletal elements in the light-driven translocation of proteins in rod photoreceptors.	2005 Nov	16249472
Bioactive natural and semisynthetic latrunculins.	2006 Feb	16499319
Actin disruption agents induce phosphorylation of histone H2AX in human breast adenocarcinoma MCF-7 cells.	2011 May	21399880
Inhibition of actin polymerisation by low concentration Latrunculin B affects endocytosis and alters exocytosis in shank and tip of tobacco pollen tubes.	2012 Sep	22288466
Counteracting the activation of pAkt by inhibition of MEK/Erk inhibition reduces actin disruption-mediated apoptosis in PTEN-null PC3M prostate cancer cell lines.	2013 Nov	24179529
Microtubule-dependent transport of vimentin filament precursors is regulated by actin and by the concerted action of Rho- and p21-activated kinases.	2014 Jul	24652946
Morphological effects on expression of growth differentiation factor 15 (GDF15), a marker of metastasis.	2014 Mar	23996089
Latrunculin B Reduces Intraocular Pressure in Human Ocular Hypertension and Primary Open-Angle Glaucoma.	2014 Sep	25237590
Small-Molecule Inhibition of Rho/MKL/SRF Transcription in Prostate Cancer Cells: Modulation of Cell Cycle, ER Stress, and Metastasis Gene Networks.	2016 May 28	27600078

Patents

Sample Use Guides

In Vivo Use Guide

Lat-B ophthalmic solutions, 0.005%, 0.01%, 0.02%, or 0.05% in one eye over 3 days (5 single-dose instillations, separated by 12 hours).

Route of Administration: Topical

In Vitro Use Guide

PC-3 cells were treated with 0.5 uM of Latrunculin B under serum-starved conditions (0.5% FBS) for 24 h and gene expression assessed with an Affymetrix gene chip. Latrunculin B produced significant effects on expression of genes involved in purine and pyrimidine metabolism.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 18:04:55 GMT 2023` Edited by `admin` on `Fri Dec 15 18:04:55 GMT 2023`
Record UNII	LW7U308U7U
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LATRUNCULIN B

Common Name

English

LATRUNCULIN B [MI]

Common Name

English

INS115644

Code

English

NSC-339663

Code

English

INS-115644

Code

English

2-THIAZOLIDINONE, 4-(15-HYDROXY-5,10-DIMETHYL-3-OXO-2,14-DIOXABICYCLO(11.3.1)HEPTADECA-4,8-DIEN-15-YL)-, (1R-(1R*,4Z,8Z,10S*,13R*,15R*(R*)))-

Common Name

English

LAT-B

Brand Name

English

2-THIAZOLIDINONE, 4-((1R,4Z,8Z,10S,13R,15R)-15-HYDROXY-5,10-DIMETHYL-3-OXO-2,14-DIOXABICYCLO(11.3.1)HEPTADECA-4,8-DIEN-15-YL)-, (4R)-

Systematic Name

English

Code System Code Type Description

CHEBI

49703