Plicamycin

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C52H76O24
Molecular Weight	1085.1454
Optical Activity	UNSPECIFIED
Defined Stereocenters	25 / 25
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CO[C@@H]([C@@H]1CC2=C(C(=O)[C@H]1O[C@H]3C[C@@H](O[C@H]4C[C@@H](O[C@H]5C[C@](C)(O)[C@H](O)[C@@H](C)O5)[C@@H](O)[C@@H](C)O4)[C@H](O)[C@@H](C)O3)C(O)=C6C(C=C(O[C@H]7C[C@@H](O[C@H]8C[C@@H](O)[C@H](O)[C@@H](C)O8)[C@H](O)[C@@H](C)O7)C(C)=C6O)=C2)C(=O)[C@@H](O)[C@@H](C)O

InChI

InChIKey=CFCUWKMKBJTWLW-BKHRDMLASA-N

InChI=1S/C52H76O24/c1-18-29(72-34-14-30(43(58)21(4)68-34)73-33-13-28(54)42(57)20(3)67-33)12-26-10-25-11-27(49(66-9)48(63)41(56)19(2)53)50(47(62)39(25)46(61)38(26)40(18)55)76-36-16-31(44(59)23(6)70-36)74-35-15-32(45(60)22(5)69-35)75-37-17-52(8,65)51(64)24(7)71-37/h10,12,19-24,27-28,30-37,41-45,49-51,53-61,64-65H,11,13-17H2,1-9H3/t19-,20-,21-,22-,23-,24-,27+,28-,30-,31-,32-,33+,34+,35+,36+,37+,41+,42-,43-,44-,45+,49+,50+,51-,52+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C52H76O24
Molecular Weight	1085.1454
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	25 / 25
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.drugs.com/cons/plicamycin-intravenous.html
Curator's Comment: description was created based on several sources, including: http://www.drugbank.ca/drugs/DB06810 https://en.wikipedia.org/wiki/Plicamycin http://www.rxlist.com/mithracin-drug/clinical-pharmacology.htm

Plicamycin (INN, also known as mithramycin; trade name Mithracin) is an antineoplastic antibiotic produced by Streptomyces plicatus. Plicamycin belongs to the group of medicines known as antineoplastics. It may be used to treat certain types of cancer. It is also used to treat hypercalcemia or hypercalciuria (too much calcium in the blood or urine) that may occur with some types of cancer. Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although this use is not included in product labeling, plicamycin is used in certain patients with the following medical condition:Paget's disease of the bone. The manufacturer discontinued plicamycin in 2000. Several different structures are currently reported in different places all with the same chromomycin core, but with different stereochemistry in the glycoside chain, a 1999 study has re-investigated the compound and proposed a revised structure. Although the exact mechanism by which Mithracin (plicamycin) causes tumor inhibition is not yet known, studies have indicated that this compound forms a complex with deoxyribonucleic acid (DNA) and inhibits cellular ribonucleic acid (RNA) and enzymic RNA synthesis. The binding of Mithracin (plicamycin) to DNA in the presence of Mg + + (or other divalent cations) is responsible for the inhibition of DNA-dependent or DNA-directed RNA synthesis. This action presumably accounts for the biological properties of Mithracin (plicamycin). Plicamycin may also lower calcium serum levels by inhibiting the effect of parathyroid hormone upon osteoclasts or by blocking the hypercalcemic action of pharmacologic doses of vitamin D.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 282 Target ID: CHEMBL2311221 Sources: http://www.drugbank.ca/drugs/DB06810	Antagonist 2849		400.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Testicular cancer 7 Sources: http://www.drugs.com/mtm/plicamycin.html	Primary		Approved 8583	MITHRACIN Approved Use Plicamycin Launch Date 1970
Hypercalcemia or hypercalciuria 1 Sources: http://www.drugs.com/cons/plicamycin-intravenous.html	Secondary		Approved 8583	MITHRACIN Approved Use Plicamycin Launch Date 1970

C_max

Value	Dose	Co-administered	Analyte	Population
350 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1412612/	1 mg/m² single, intravenous dose: 1 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		PLICAMYCIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1489 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1412612/	1 mg/m² single, intravenous dose: 1 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		PLICAMYCIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
10.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1412612/	1 mg/m² single, intravenous dose: 1 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		PLICAMYCIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
17.5 ug/kg 1 times / day multiple, intravenous Studied dose Dose: 17.5 ug/kg, 1 times / day Route: intravenous Route: multiple Dose: 17.5 ug/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28735378	unhealthy, 19-22 Health Status: unhealthy Age Group: 19-22 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/28735378	Other AEs: Aspartate aminotransferase increase, Alanine aminotransferase increase... Other AEs: Aspartate aminotransferase increase (grade 3, 100%) Alanine aminotransferase increase (grade 3, 100%) Sources: https://pubmed.ncbi.nlm.nih.gov/28735378
25 ug/kg 1 times / day multiple, intravenous MTD Dose: 25 ug/kg, 1 times / day Route: intravenous Route: multiple Dose: 25 ug/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28735378	unhealthy, 24-35 Health Status: unhealthy Age Group: 24-35 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/28735378	Disc. AE: Hepatotoxicity, Aspartate aminotransferase increase... AEs leading to discontinuation/dose reduction: Hepatotoxicity (grade 3, 100%) Aspartate aminotransferase increase (grade 4, 100%) Alanine aminotransferase increase (grade 4, 100%) Lactate dehydrogenase increased (100%) Fever (100%) Nausea (100%) Sources: https://pubmed.ncbi.nlm.nih.gov/28735378

AEs

AE	Significance	Dose	Population
Alanine aminotransferase increase	grade 3, 100%	17.5 ug/kg 1 times / day multiple, intravenous Studied dose Dose: 17.5 ug/kg, 1 times / day Route: intravenous Route: multiple Dose: 17.5 ug/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28735378	unhealthy, 19-22 Health Status: unhealthy Age Group: 19-22 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/28735378
Aspartate aminotransferase increase	grade 3, 100%	17.5 ug/kg 1 times / day multiple, intravenous Studied dose Dose: 17.5 ug/kg, 1 times / day Route: intravenous Route: multiple Dose: 17.5 ug/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28735378	unhealthy, 19-22 Health Status: unhealthy Age Group: 19-22 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/28735378
Fever	100% Disc. AE	25 ug/kg 1 times / day multiple, intravenous MTD Dose: 25 ug/kg, 1 times / day Route: intravenous Route: multiple Dose: 25 ug/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28735378	unhealthy, 24-35 Health Status: unhealthy Age Group: 24-35 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/28735378
Lactate dehydrogenase increased	100% Disc. AE	25 ug/kg 1 times / day multiple, intravenous MTD Dose: 25 ug/kg, 1 times / day Route: intravenous Route: multiple Dose: 25 ug/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28735378	unhealthy, 24-35 Health Status: unhealthy Age Group: 24-35 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/28735378
Nausea	100% Disc. AE	25 ug/kg 1 times / day multiple, intravenous MTD Dose: 25 ug/kg, 1 times / day Route: intravenous Route: multiple Dose: 25 ug/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28735378	unhealthy, 24-35 Health Status: unhealthy Age Group: 24-35 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/28735378
Hepatotoxicity	grade 3, 100% Disc. AE	25 ug/kg 1 times / day multiple, intravenous MTD Dose: 25 ug/kg, 1 times / day Route: intravenous Route: multiple Dose: 25 ug/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28735378	unhealthy, 24-35 Health Status: unhealthy Age Group: 24-35 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/28735378
Alanine aminotransferase increase	grade 4, 100% Disc. AE	25 ug/kg 1 times / day multiple, intravenous MTD Dose: 25 ug/kg, 1 times / day Route: intravenous Route: multiple Dose: 25 ug/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28735378	unhealthy, 24-35 Health Status: unhealthy Age Group: 24-35 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/28735378
Aspartate aminotransferase increase	grade 4, 100% Disc. AE	25 ug/kg 1 times / day multiple, intravenous MTD Dose: 25 ug/kg, 1 times / day Route: intravenous Route: multiple Dose: 25 ug/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28735378	unhealthy, 24-35 Health Status: unhealthy Age Group: 24-35 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/28735378

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BSEP 550		OATP1B1 29

Drug as perpetrator

Target	Modality	Activity
BSEP 554	inhibitor 4027 Sources: https://molpharm.aspetjournals.org/content/96/2/158	no
BSEP 554	supressor 160 Sources: https://molpharm.aspetjournals.org/content/96/2/158	yes
MDR3 9	supressor 160 Sources: https://molpharm.aspetjournals.org/content/96/2/158	yes
MRP2 625	supressor 160 Sources: https://molpharm.aspetjournals.org/content/96/2/158	yes
MRP3 326	supressor 160 Sources: https://molpharm.aspetjournals.org/content/96/2/158	yes
MRP4 345	supressor 160 Sources: https://molpharm.aspetjournals.org/content/96/2/158	yes
NTCP 40	supressor 160 Sources: https://molpharm.aspetjournals.org/content/96/2/158	yes
OATP1B1 1095	inducer 1966 Sources: https://molpharm.aspetjournals.org/content/96/2/158	yes
OATP1B3 970	supressor 160 Sources: https://molpharm.aspetjournals.org/content/96/2/158	yes
P-gp 1932	supressor 160 Sources: https://molpharm.aspetjournals.org/content/96/2/158	yes

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA00I1CR	https://www.aablocks.com/goods/Goods/detail?id=AA00I1CR
Aaron Chemicals	AR00I24J	http://www.aaronchem.com/18378-89-7
abcr GmbH	AB181177	http://www.abcr.de/shop/en/AB181177
AbMole Bioscience	M9262	http://www.abmole.com/products/plicamycin.html
AK Scientific, Inc. (AKSCI)	V0247	http://www.aksci.com/item_detail.php?cat=V0247
Alfa Chemistry	AP18378897	https://reagents.alfa-chemistry.com/product/mithramycin-a-from-streptomyces-plicatus-cas-18378-89-7-6838.html
Ambinter	Amb19930490	http://www.ambinter.com/reference/19930490
Aurora Fine Chemicals LLC	A17.878.160	http://online.aurorafinechemicals.com/info?ID=A17.878.160
BioChemPartner	BCP22028	http://www.biochempartner.com/18378-89-7-BCP22028
BioCrick	BCC2470	http://www.biocrick.com/Mithramycin-A-BCC2470.html
BioSynth	J-011777	https://www.biosynth.com/en/products/all-products/products/J-011777.html
BOC Sciences	18378-89-7	https://adc.bocsci.com/product/mithramycin-a-cas-18378-89-7-465333.html
Chem Scene	CS-0014261	http://www.chemscene.com/18378-89-7.html
Chemspace	CSSB02495362970	https://chem-space.com/CSSB02495362970
Chemspace	CSSS00161189713	https://chem-space.com/CSSS00161189713
DC Chemicals	DC21517	http://www.dcchemicals.com/product_show-DC21517.html
eNovation Chemicals	D672652	https://www.enovationchem.com/ProductDetails.asp?ProductID=D672652
Finetech	FT-0628952	http://www.finetechnology-ind.com/prod/detail/pub/18378-89-7.html
Glentham Life Sciences	GA1050	http://www.glentham.com/products/product/GA1050/
MedChem Express	HY-A0122	https://www.medchemexpress.com/Plicamycin.html
Molcore	MC534339	https://www.molcore.com/product/18378-89-7
MolPort	MolPort-008-268-165	https://www.molport.com/shop/molecule-link/MolPort-008-268-165
MolPort	MolPort-046-418-519	https://www.molport.com/shop/molecule-link/MolPort-046-418-519
Sigma-Aldrich	M6891_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/m6891?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S548117	http://www.smolecule.com/products/s548117
THE BioTek	bt-287453	https://www.thebiotek.com/product/inhibitors/bt-287453

PubMed

Title	Date	PubMed
TGF-beta-induced expression of tissue inhibitor of metalloproteinases-3 gene in chondrocytes is mediated by extracellular signal-regulated kinase pathway and Sp1 transcription factor.	2005-05	15468069
Elucidation of the glycosylation sequence of mithramycin biosynthesis: isolation of 3A-deolivosylpremithramycin B and its conversion to premithramycin B by glycosyltransferase MtmGII.	2005-04	15712316
Sp1 and Sp3 transcription factors upregulate the proximal promoter of the human prostate-specific antigen gene in prostate cancer cells.	2005-03-15	15708372
Binding of (MTR)2Zn2+ complex to chromatin: a comparison with (MTR)2Mg2+ complex.	2005-03	15708791
Effect of pitavastatin on transactivation of human serum paraoxonase 1 gene.	2005-02	15690306
Ets1 is an effector of protein kinase Calpha in cancer cells.	2005-01-20	15531915
Transcriptional regulation of the human DNA methyltransferase 3A and 3B genes by Sp3 and Sp1 zinc finger proteins.	2005-01-15	15362956
Calculation of binding length of base-specific DNA dyes by comparison of sequence and flow cytometric data. Application to Oryza sativa and Arabidopsis thaliana.	2005-01-07	15498596
Effect of complex formation between Zn2+ ions and the anticancer drug mithramycin upon enzymatic activity of zinc(II)-dependent alcohol dehydrogenase.	2005-01	15650873
Both Sp1 and Smad participate in mediating TGF-beta1-induced HGF receptor expression in renal epithelial cells.	2005-01	15339794
Inhibition of p53-mediated transcriptional responses by mithramycin A.	2004-12-09	15489892
Sp1 is involved in the transcriptional activation of lysozyme in epithelial cells.	2004-11-26	15504356
Chemotherapy for the brain: the antitumor antibiotic mithramycin prolongs survival in a mouse model of Huntington's disease.	2004-11-17	15548647
Transforming growth factor-beta1-dependent activation of Smad2/3 and up-regulation of PAI-1 expression is negatively regulated by Src in SKOV-3 human ovarian cancer cells.	2004-10-15	15372629
Transforming growth factor beta stimulation of biglycan gene expression is potentially mediated by sp1 binding factors.	2004-10-15	15372625
Roles of Sp1 and protein kinase C in regulation of human serum paraoxonase 1 (PON1) gene transcription in HepG2 cells.	2004-10	15380450
Transcriptional regulation of the human beta-1,4-galactosyltransferase V gene in cancer cells: essential role of transcription factor Sp1.	2004-09-17	15263012
Rapamycin-mediated induction of gamma-globin mRNA accumulation in human erythroid cells.	2004-08	15287957
Tailoring modification of deoxysugars during biosynthesis of the antitumour drug chromomycin A by Streptomyces griseus ssp. griseus.	2004-08	15255901
Systematic review of bisphosphonates for hypercalcaemia of malignancy.	2004-07	15332420
Regulation of the human secretin gene is controlled by the combined effects of CpG methylation, Sp1/Sp3 ratio, and the E-box element.	2004-07	15118068
Involvement of Sp1 and SREBP-1a in transcriptional activation of the LDL receptor gene by insulin and LH in cultured porcine granulosa-luteal cells.	2004-07	14998783
The anticancer drug mithramycin A sensitises tumour cells to apoptosis induced by tumour necrosis factor (TNF).	2004-05-17	15138489
Concentration-dependent effects of endogenous S-nitrosoglutathione on gene regulation by specificity proteins Sp3 and Sp1.	2004-05-15	14766015
Tumor necrosis factor-alpha induces fractalkine expression preferentially in arterial endothelial cells and mithramycin A suppresses TNF-alpha-induced fractalkine expression.	2004-05	15111313
SP-transcription factors are involved in basal MVP promoter activity and its stimulation by HDAC inhibitors.	2004-04-23	15047174
N-terminal tail domains of core histones in nucleosome block the access of anticancer drugs, mithramycin and daunomycin, to the nucleosomal DNA.	2004-04-01	15059665
Identification and characterization of a phorbol ester-responsive element in the murine 8S-lipoxygenase gene.	2004-03-19	14711820
Tenascin-C upregulation by transforming growth factor-beta in human dermal fibroblasts involves Smad3, Sp1, and Ets1.	2004-03-04	15001984
MtmMII-mediated C-methylation during biosynthesis of the antitumor drug mithramycin is essential for biological activity and DNA-drug interaction.	2004-02-27	14660589
bcl-2 induction of urokinase plasminogen activator receptor expression in human cancer cells through Sp1 activation: involvement of ERK1/ERK2 activity.	2004-02-20	14660675
Cloning, characterisation and identification of several polymorphisms in the promoter region of the human alpha2B-adrenergic receptor gene.	2004-02-01	15037199
Bucillamine induces the synthesis of vascular endothelial growth factor dose-dependently in systemic sclerosis fibroblasts via nuclear factor-kappaB and simian virus 40 promoter factor 1 pathways.	2004-02	14742681
Biosynthesis of the antitumor chromomycin A3 in Streptomyces griseus: analysis of the gene cluster and rational design of novel chromomycin analogs.	2004-01	15112992
Aureolic acids: similar antibiotics with different biosynthetic gene clusters.	2004-01	15112986
Asbestos induces tissue factor in Beas-2B human lung bronchial epithelial cells in vitro.	2004	15636197
A systematic review of the role of bisphosphonates in metastatic disease.	2004	14960258
Pervilleine F, a new tropane alkaloid aromatic ester that reverses multidrug resistance.	2003-12-12	14666656
Involvement of reactive oxygen species and SP-1 in fibronectin production by oxidized LDL.	2003-10-17	14521937
Expression of p21(WAF1/Cip1) through Sp1 sites by histone deacetylase inhibitor apicidin requires PI 3-kinase-PKC epsilon signaling pathway.	2003-09-04	12955081
Accumulation of gamma-globin mRNA in human erythroid cells treated with angelicin.	2003-09	12930320
Enhanced binding of Sp1/Sp3 transcription factors mediates the hyperoxia-induced increased expression of the lung type I cell gene T1alpha.	2003-08-01	12874823
Inhibition of c-src transcription by mithramycin: structure-activity relationships of biosynthetically produced mithramycin analogues using the c-src promoter as target.	2003-07-15	12846580
c-Myc oncoprotein: cell cycle-related events and new therapeutic challenges in cancer and cardiovascular diseases.	2003-07-10	12851483
Association of chromatin with anticancer antibiotics, mithramycin and chromomycin A3.	2003-07-03	12788353
Furoquinoline alkaloids and cytotoxic constituents from the leaves of Melicope semecarpifolia.	2003-06	12865974
The large linear plasmid pSLA2-L of Streptomyces rochei has an unusually condensed gene organization for secondary metabolism.	2003-06	12791134
Stereoselective synthesis of functionalized precursors of the CDEF and CDE 2,6-dideoxy-tetra- and trisaccharide units of durhamycins A and B.	2003-05-29	12762675
Anthracyclines.	2003	15338739
MITHRAMYCIN IN THE TREATMENT OF DISSEMINATED TESTICULAR NEOPLASMS.	1965-01-21	14224214

Patents

Sample Use Guides

In Vivo Use Guide

15-25 ug/kg bw

Route of Administration: Intravenous

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:36:43 GMT 2025` Edited by `admin` on `Mon Mar 31 17:36:43 GMT 2025`
Record UNII	NIJ123W41V
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

MITHRACIN

Preferred Name

English

Plicamycin

Official Name

English

PLICAMYCIN [USAN]

Common Name

English

A-2371

Code

English

PLICAMYCIN [HSDB]

Common Name

English

PLICAMYCIN [ORANGE BOOK]

Common Name

English

PA-144

Code

English

AUREOLIC ACID

Common Name

English

LA-7017

Code

English

ANTIBIOTIC LA-7017

Code

English

MITHRAMYCIN

Common Name

English

PLICAMYCIN [MART.]

Common Name

English

MITHRAMYCIN A

Common Name

English

NSC-24559

Code

English

plicamycin [INN]

Common Name

English

PLICAMYCIN [USP IMPURITY]

Common Name

English

Plicamycin [WHO-DD]

Common Name

English

PLICAMYCIN [MI]

Common Name

English

PLICAMYCIN [VANDF]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2115