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

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
Effects of cytochalasin D and latrunculin B on mechanical properties of cells.	2001 Mar	11181185
Rho/ROCK pathway contributes to the activation of extracellular signal-regulated kinase/GATA-4 during myocardial cell hypertrophy.	2002 Mar 8	11739382
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
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.

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