Cat. No.: HY-13906

Largazole

(Synonyms: (+)-Largazole)

Largazole ((+)-Largazole) is an orally active, blood-brain barrier-permeable class I histone deacetylase (HDAC) inhibitor with in vivo anticancer activity and osteogenic efficacy. As a prodrug, Largazole hydrolyzes to Largazole thiol (HY-170890), which has a K_i value of 0.07 nM against human HDAC2. Largazole regulates the cell cycle, induces apoptosis, upregulates tumor suppressors and osteoblast differentiation markers, inhibits osteoclast formation, and upregulates neuroprotection-related genes. Largazole can be used in the research of various cancers including colorectal cancer, as well as neurodegenerative diseases.

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CAS No.: 1009815-87-5
Formule: C₂₉H₄₂N₄O₅S₃
Masse moléculaire:622.86

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Please store the product under the recommended conditions in the Certificate of Analysis.

Data Sheet (278 KB)

Largazole Chemical Structure

CAS No.: 1009815-87-5

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Activité biologique
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Pureté et documentation
Références
Calculators
Help & FAQs
Classifications
Bioz

Activité biologique

Description

IC₅₀ & Target

HDAC-2

0.07 nM (IC₅₀)

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RUNX1
RUNX2

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Cellular Effect

Cell Line	Type	Value	Description	References
16HBE14o-	IC₅₀	>10 μM Compound: 1	Cytotoxicity against human 16HBE cells after 48 hrs by CCK-8 assay Cytotoxicity against human 16HBE cells after 48 hrs by CCK-8 assay	[PMID: 24900585]
A549	GI₅₀	1.46 μM Compound: 158a	Antiproliferative activity against human A549 cells Antiproliferative activity against human A549 cells	[PMID: 31926469]
A549	IC₅₀	0.077 μM Compound: 1	Cytotoxicity against human A549 cells after 48 hrs by CCK-8 assay Cytotoxicity against human A549 cells after 48 hrs by CCK-8 assay	[PMID: 24900585]
A549	IC₅₀	0.46 μM Compound: Largazole	Antiproliferative activity against human A549 cells assessed as reduction in cell viability after 72 hrs by MTT assay Antiproliferative activity against human A549 cells assessed as reduction in cell viability after 72 hrs by MTT assay	[PMID: 31505452]
DU-145	GI₅₀	11 nM Compound: 7	Antiproliferative activity against human DU145 cells after 72 hrs by CCK8 assay Antiproliferative activity against human DU145 cells after 72 hrs by CCK8 assay	[PMID: 26331334]
HCT-116	GI₅₀	0.065 μM Compound: 5	Growth inhibition of human HCT-116 cells incubated for 96 hrs by MTS assay Growth inhibition of human HCT-116 cells incubated for 96 hrs by MTS assay	[PMID: 27809521]
HCT-116	GI₅₀	10 nM Compound: 1	Growth inhibition of human HCT116 cells after 96 hrs by MTS assay Growth inhibition of human HCT116 cells after 96 hrs by MTS assay	[PMID: 21936551]
HCT-116	IC₅₀	0.044 μM Compound: Largazole	Antiproliferative activity against human HCT116 cells assessed as reduction in cell viability after 72 hrs by MTT assay Antiproliferative activity against human HCT116 cells assessed as reduction in cell viability after 72 hrs by MTT assay	[PMID: 31505452]
HCT-116	IC₅₀	0.39 μM Compound: 158a	Antiproliferative activity against human HCT-116 cells assessed as reduction in cell viability Antiproliferative activity against human HCT-116 cells assessed as reduction in cell viability	[PMID: 31926469]
HCT-116	IC₅₀	18 nM Compound: 3	Cytotoxicity against human HIF1alpha and HIF2alpha deficit HCT116 cells assessed as reduction in cell viability measured after 48 hrs by ATPlite 1step luminescence assay Cytotoxicity against human HIF1alpha and HIF2alpha deficit HCT116 cells assessed as reduction in cell viability measured after 48 hrs by ATPlite 1step luminescence assay	[PMID: 27380142]
HCT-116	IC₅₀	20 nM Compound: 5	Cytotoxicity against human HCT116 cells assessed as reduction in cell viability after 48 hrs by MTT assay Cytotoxicity against human HCT116 cells assessed as reduction in cell viability after 48 hrs by MTT assay	[PMID: 28416100]
HCT-116	IC₅₀	3.7 nM Compound: 3	Cytotoxicity against oncogenic KRAS knockout human HCT116 cells expressing wild type KRAS assessed as reduction in cell viability measured after 48 hrs by ATPlite 1step luminescence assay Cytotoxicity against oncogenic KRAS knockout human HCT116 cells expressing wild type KRAS assessed as reduction in cell viability measured after 48 hrs by ATPlite 1step luminescence assay	[PMID: 27380142]
HCT-116	IC₅₀	6.41 nM Compound: 3	Cytotoxicity against human HCT116 cells assessed as reduction in cell viability measured after 48 hrs by ATPlite 1step luminescence assay Cytotoxicity against human HCT116 cells assessed as reduction in cell viability measured after 48 hrs by ATPlite 1step luminescence assay	[PMID: 27380142]
HEK293	GI₅₀	>100 μM Compound: 158a	Antiproliferative activity against human HEK293 cells Antiproliferative activity against human HEK293 cells	[PMID: 31926469]
MDA-MB-231	IC₅₀	1.6 nM Compound: 5	Cytotoxicity against human MDA-MB-231 cells assessed as reduction in cell viability after 48 hrs by MTT assay Cytotoxicity against human MDA-MB-231 cells assessed as reduction in cell viability after 48 hrs by MTT assay	[PMID: 28416100]
MDA-MB-231	IC₅₀	4.75 μM Compound: Largazole	Antiproliferative activity against human MDA-MB-231 cells assessed as reduction in cell viability after 72 hrs by MTT assay Antiproliferative activity against human MDA-MB-231 cells assessed as reduction in cell viability after 72 hrs by MTT assay	[PMID: 31505452]
MOLT-4	GI₅₀	16.2 nM Compound: 7	Antiproliferative activity against human MOLT4 cells after 72 hrs by CCK8 assay Antiproliferative activity against human MOLT4 cells after 72 hrs by CCK8 assay	[PMID: 26331334]
NCI-H1975	IC₅₀	0.083 μM Compound: 1	Cytotoxicity against human NCI-H1975 cells after 48 hrs by CCK-8 assay Cytotoxicity against human NCI-H1975 cells after 48 hrs by CCK-8 assay	[PMID: 24900585]
NCI-H460	IC₅₀	0.12 μM Compound: 1	Cytotoxicity against human NCI-H460 cells after 48 hrs by CCK-8 assay Cytotoxicity against human NCI-H460 cells after 48 hrs by CCK-8 assay	[PMID: 24900585]
Sf9	IC₅₀	120 nM Compound: Largazole	Inhibition of full length C-terminal His-tagged human HDAC8 expressed in baculovirus infected Sf9 cells using Ac-peptide-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 240 mins by fluorescence based assay Inhibition of full length C-terminal His-tagged human HDAC8 expressed in baculovirus infected Sf9 cells using Ac-peptide-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 240 mins by fluorescence based assay	[PMID: 31505452]
Sf9	IC₅₀	1520 nM Compound: Largazole	Inhibition of recombinant full length human HDAC2 expressed in baculovirus infected Sf9 cells using Ac-peptide-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence based assay Inhibition of recombinant full length human HDAC2 expressed in baculovirus infected Sf9 cells using Ac-peptide-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence based assay	[PMID: 31505452]
Sf9	IC₅₀	2002 nM Compound: Largazole	Inhibition of human recombinant full length C-terminal His-tagged HDAC3 (1 to 428 residues)/N-terminal GST-tagged NCOR2 (395 to 489 residues) expressed in baculovirus infected Sf9 cells using Ac-peptide-AMC as substrate preincubated for 15 mins followed b Inhibition of human recombinant full length C-terminal His-tagged HDAC3 (1 to 428 residues)/N-terminal GST-tagged NCOR2 (395 to 489 residues) expressed in baculovirus infected Sf9 cells using Ac-peptide-AMC as substrate preincubated for 15 mins followed b	[PMID: 31505452]
Sf9	IC₅₀	228 nM Compound: Largazole	Inhibition of recombinant full length C-terminal FLAG/His-tagged human HDAC1 expressed in baculovirus infected Sf9 cells using Ac-peptide-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence b Inhibition of recombinant full length C-terminal FLAG/His-tagged human HDAC1 expressed in baculovirus infected Sf9 cells using Ac-peptide-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence b	[PMID: 31505452]
SK-OV-3	IC₅₀	0.25 μM Compound: Largazole	Antiproliferative activity against human SKOV3 cells assessed as reduction in cell viability after 72 hrs by MTT assay Antiproliferative activity against human SKOV3 cells assessed as reduction in cell viability after 72 hrs by MTT assay	[PMID: 31505452]
U-937	GI₅₀	16.8 nM Compound: 7	Antiproliferative activity against human U937 cells after 72 hrs by CCK8 assay Antiproliferative activity against human U937 cells after 72 hrs by CCK8 assay	[PMID: 26331334]
WI-38	GI₅₀	82.5 nM Compound: 7	Antiproliferative activity against human WI38 cells after 72 hrs by CCK8 assay Antiproliferative activity against human WI38 cells after 72 hrs by CCK8 assay	[PMID: 26331334]

In Vitro

Largazole is a prodrug, with potency against HDAC1 approximately 10-fold lower than that of its active metabolite Largazole thiol (HY-170890) and potency against HDAC6 two orders of magnitude lower; Largazole potently inhibits human class I HDAC subtypes HDAC1, HDAC2, and HDAC3, with K_i values of 20 nM, 21 nM, and 48 nM, respectively; Largazole thiol potently inhibits purified human HDAC2, with a K_i value of 0.07 nM^[1]^[2]^[3].
Largazole induces acetylation of histone H3 (Lys9/14) in HCT116 colon cancer cells at nanomolar low concentrations, but does not alter the acetylation level of α-tubulin (Lys40) even at concentrations as high as 10 μM, which reflects its selective inhibitory activity against class I HDACs^[1].
Largazole dose-dependently induces osteoblast differentiation by upregulating Runx2 and BMPs, while inhibiting osteoclast formation, exhibiting dual activities of stimulating bone formation and suppressing bone resorption^[1].
Largazole (0.3 μM; 12 h) increases the expression level of the BDNF gene by 1.4-fold in SF-268 glioblastoma cells^[2].
Largazole inhibits the growth of various cancer cell lines at nanomolar concentrations, while exhibiting significantly lower inhibitory activity against non-transformed epithelial cells and fibroblasts, demonstrating selective targeting of transformed cells^[1].
Largazole (incubated for 48 h) potently inhibits the proliferation of SF-268 and SF-295 glioblastoma (GBM) cells with IC₅₀ values of 62 nM and 68 nM, respectively; it also potently inhibits the proliferation of SH-SY5Y neuroblastoma cells with an IC₅₀ value of 102 nM^[2].
Largazole potently inhibits the growth of transformed human MDA-MB-231, U2OS, HT29, and IMR-32 cells (GI₅₀ values 7.7 nM, 55 nM, 12 nM, and 16 nM, respectively), and exhibits selective activity relative to untransformed NMuMG and NIH3T3 cells; it also potently inhibits the proliferation of cultured human malignant melanoma cell lines in vitro^[3]^[4].
Largazole induces cell cycle arrest (G1 phase arrest at 3 nM, G2/M phase arrest at concentrations >30 nM) and triggers apoptosis at concentrations >30 nM by regulating cell cycle inhibitors, CDKs/cyclins, and pro-apoptotic BCL2 family proteins in HCT116 colon cancer cells and NB4 leukemia cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Real Time qPCR^[2]

Cell Line:

SF-295 glioblastoma multiforme (GBM) cells
Concentration:

0.3 μM
Incubation Time:

12 h
Result:

Increased BDNF gene expression by 1.4-fold.

In Vivo

Largazole (i.p.) demonstrates in vivo anticancer activity in HCT116 colon cancer xenografts by downregulating IRS-1 and compromising IGF signaling, with no observed acute toxicity^[1].
Largazole (local implantation via collagen sponge) induces in vivo woven bone formation in a mouse calvarial bone formation model when delivered via collagen sponge implantation^[1].
Largazole (local application via MBCPs) enhances in vivo bone fracture healing in a rabbit calvarial model when combined with MBCPs, promoting direct contact bone formation^[1].
Largazole (5-200 mg/kg; i.p.; p.o.; single dose; daily; 4 consecutive days) crosses the blood-brain barrier in healthy mice, achieves therapeutically relevant brain concentrations of its active form Largazole thiol, upregulates neuroprotective genes including Bdnf, Pax6, and Oprm1, and predicts beneficial effects on nervous system function while exhibiting low acute and repeated-dose toxicity^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

non-tumor bearing^[2]
Dosage:

5 mg/kg (single i.p.); 10 mg/kg (single i.p.); 50 mg/kg (single i.p.); 50 mg/kg (single p.o.); 60 mg/kg (daily i.p.); 75 mg/kg (daily i.p.); 200 mg/kg (single i.p.)
Administration:

i.p.; single dose; daily; 4 consecutive days; p.o.
Result:

Induced slight brain histone hyperacetylation after 4 hours at 5 mg/kg single i.p..
Induced pronounced brain histone hyperacetylation after 4 hours at 50 mg/kg single i.p..
Resulted in brain largazole thiol concentrations of ~300 nM after 4 hours, decreasing to ~80 nM after 24 hours at 50 mg/kg single i.p..
Resulted in brain largazole thiol concentrations near the in vitro GBM IC₅₀ after 4 hours at 10 mg/kg single i.p. or 50 mg/kg single p.o..
Resulted in a 3.3-fold increase in brain Bdnf gene expression 12 hours post-administration at 50 mg/kg single i.p..
Identified 1220 differentially expressed genes (≥2.5-fold change, p < 0.05), including a 3.0-fold increase in Pax6 and 4.6-fold increase in Oprm1 gene expression after single i.p. dose of 50 mg/kg.
Predicted increased activation of nervous system functions (including neurogenesis, neuron development, neurite growth, cognition, and learning) and decreased activation of neurological diseases (including movement disorders, seizure disorders, ataxia, and congenital brain malformations) after single i.p. dose of 50 mg/kg.
Was well tolerated at single i.p. doses up to 200 mg/kg.
Caused no toxicity with repeated i.p. dosing of 60 mg/kg or 75 mg/kg for 4 consecutive days.

Chemical Information

CAS No. 1009815-87-5
Masse moléculaire 622.86
Formule C₂₉H₄₂N₄O₅S₃
SMILES

CCCCCCCC(SCC/C=C/[C@H](CC(NC1)=O)OC([C@H](C(C)C)NC([C@]2(C)CSC(C3=CSC1=N3)=N2)=O)=O)=O
Synonyms

(+)-Largazole
Structure Classification
- Others
Initial Source
- Microorganisms
Floridian Marine Cyanobacterium Symploca sp.
Livraison

Room temperature in continental US; may vary elsewhere.
Stockage

Please store the product under the recommended conditions in the Certificate of Analysis.

Pureté et documentation

Select Batch:

Pureté: 99.98%

Assay: 99.98%

ee.: 99.98%

Fiche technique (278 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Instruction de manipulation (2659 KB)

Références

[1]. Hong J, et al. Largazole: from discovery to broad-spectrum therapy. Natural product reports. 2012 Apr;29(4):449-56.

[2]. Al-Awadhi FH, et al. Largazole is a Brain-Penetrant Class I HDAC Inhibitor with Extended Applicability to Glioblastoma and CNS Diseases. ACS chemical neuroscience. 2020 Jul 01;11(13):1937-1943. [Content Brief]

[3]. Bowers A, et al. Total synthesis and biological mode of action of largazole: a potent class I histone deacetylase inhibitor. Journal of the American Chemical Society. 2008 Aug 20;130(33):11219-22.

[4]. Taori K, et al. Structure and Activity of Largazole, a Potent Antiproliferative Agent from the Floridian Marine Cyanobacterium Symploca sp. Journal of the American Chemical Society, 2008, 130(6): 1806-1807.

Calculators

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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Largazole

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Activité biologique

Chemical Information

Pureté et documentation

Références

Calculators

Help & FAQs

Largazole Related Classifications

HY-13906 Related Classifications