FLUVASTATIN SODIUM

Details

Stereochemistry	RACEMIC
Molecular Formula	C24H25FNO4.Na
Molecular Weight	433.4478
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].CC(C)N1C(\C=C\[C@H](O)C[C@H](O)CC([O-])=O)=C(C2=C1C=CC=C2)C3=CC=C(F)C=C3

InChI

InChIKey=ZGGHKIMDNBDHJB-RPQBTBOMSA-M

InChI=1S/C24H26FNO4.Na/c1-15(2)26-21-6-4-3-5-20(21)24(16-7-9-17(25)10-8-16)22(26)12-11-18(27)13-19(28)14-23(29)30;/h3-12,15,18-19,27-28H,13-14H2,1-2H3,(H,29,30);/q;+1/p-1/b12-11+;/t18-,19-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	Na
Molecular Weight	22.9898
Charge	1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C24H25FNO4
Molecular Weight	410.458
Charge	-1
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021192s019lbl.pdf | https://www.drugbank.ca/drugs/DB01095

Fluvastatin is an antilipemic agent that competitively inhibits hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. Fluvastatin is marketed under the trade names Lescol, Canef, Vastin. LESCOL/LESCOL XL is an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: Reduce elevated TC, LDL-C, Apo B, and TG, and to increase HDL-C in adult patients with primary hypercholesterolemia and mixed dyslipidemia Reduce elevated TC, LDL-C, and Apo B levels in boys and post-menarchal girls, 10 to 16 years of age, with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy Reduce the risk of undergoing revascularization procedures in patients with clinically evident CHD Slow the progression of atherosclerosis in patients with CHD. Fluvastatin selectively and competitively inhibits the hepatic enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate, the rate-limiting step in cholesterol biosynthesis. Inhibition results in a decrease in hepatic cholesterol levels which stimulates the synthesis of LDL receptors and increases hepatic uptake of LDL cholesterol. The end result is decreased levels of plasma total and LDL cholesterol.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
HMG-CoA reductase 47 Target ID: CHEMBL402 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021192s019lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/10965989	Inhibitor 8297		28.0 nM [IC50]
Oligopeptide transporter small intestine isoform 6 Target ID: CHEMBL4605 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15846457	Inhibitor 8297		337.0 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Hypercholesterolemia 47 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021192s019lbl.pdf	Primary	Approved 8429	LESCOL Approved Use LESCOL/LESCOL XL is an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: Reduce elevated TC, LDL-C, Apo B, and TG, and to increase HDL-C in adult patients with primary hypercholesterolemia and mixed dyslipidemia (1.1) Reduce elevated TC, LDL-C, and Apo B levels in boys and post-menarchal girls, 10 to 16 years of age, with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy (1.1) Reduce the risk of undergoing revascularization procedures in patients with clinically evident CHD (1.2) Slow the progression of atherosclerosis in patients with CHD (1.2) Launch Date 1993
Atherosclerosis 74 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021192s019lbl.pdf	Primary	Approved 8429	LESCOL Approved Use LESCOL/LESCOL XL is an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: Reduce elevated TC, LDL-C, Apo B, and TG, and to increase HDL-C in adult patients with primary hypercholesterolemia and mixed dyslipidemia (1.1) Reduce elevated TC, LDL-C, and Apo B levels in boys and post-menarchal girls, 10 to 16 years of age, with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy (1.1) Reduce the risk of undergoing revascularization procedures in patients with clinically evident CHD (1.2) Slow the progression of atherosclerosis in patients with CHD (1.2) Launch Date 1993
Dyslipidemia 30 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021192s019lbl.pdf	Primary	Approved 8429	LESCOL Approved Use LESCOL/LESCOL XL is an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: Reduce elevated TC, LDL-C, Apo B, and TG, and to increase HDL-C in adult patients with primary hypercholesterolemia and mixed dyslipidemia (1.1) Reduce elevated TC, LDL-C, and Apo B levels in boys and post-menarchal girls, 10 to 16 years of age, with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy (1.1) Reduce the risk of undergoing revascularization procedures in patients with clinically evident CHD (1.2) Slow the progression of atherosclerosis in patients with CHD (1.2) Launch Date 1993

C_max

Value	Dose	Co-administered	Analyte	Population
205 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29368187	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUVASTATIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
206.2 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29368187	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUVASTATIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.54 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29368187	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUVASTATIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
640 mg 1 times / day multiple, oral Highest studied dose Dose: 640 mg, 1 times / day Route: oral Route: multiple Dose: 640 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11336101 Page: p.505	unhealthy, ADULT n = 7 Health Status: unhealthy Condition: lipid metabolism disorder Age Group: ADULT Sex: M+F Food Status: FED Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/11336101 Page: p.505	Sources: https://pubmed.ncbi.nlm.nih.gov/11336101 Page: p.505

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478 CYP3A 214 CYP2C8 911 P-gp 1461 BCRP 699 OAT3 642 OAT1 599	CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C19 991 CYP2E1 667 CYP3A5 395 CYP1A1 349 CYP2C8 693 P-gp 1537 BCRP 561 OATP1B1 406 OATP2B1 104 OATP1B3 350	CYP1A1 108

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/8737761/ Page: 3.0	moderate [IC50 100 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2C19 1553	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP3A 298	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17064205/	not significant
CYP3A4 1925	inhibitor 3277 Sources: https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2044.2005.04110.x	weak [Ki 94.3 uM]
CYP2C8 965	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	yes [IC50 20 uM]
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/14729100/	yes [IC50 26.3 uM]
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/14729100/	yes [IC50 5.79 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	yes [Ki 0.3 uM]
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15955871/ Page: 5.0	yes [Ki 5.43 uM]
CYP1A1 218	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/8937853/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2C9 1037	substrate 3367 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	major	yes (co-administration study) Comment: Coadministration with rifampicin (CYP2C9 inducer) increased the CL/F of fluvastatin by 95% and to reduce AUC by 50%. Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract
CYP1A1 349	substrate 3367 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	minor
CYP2C8 693	substrate 3367 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	minor
CYP2D6 1217	substrate 3367 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	minor
CYP3A4 1737	substrate 3367 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract; https://pubmed.ncbi.nlm.nih.gov/17064205/	minor	unknown (co-administration study) Comment: Coadministration with cyclocporine resulted in 3.1-fold increase in AUC; however, cannot be explained through these mechanisms, since neither pravastatin nor fluvastatin has been shown to be a substrate for either P-gp or CYP3A4; coadministration with itraconazole had no significant impact on Cmax and AUC of fluvastatin Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract; https://pubmed.ncbi.nlm.nih.gov/17064205/
CYP1A2 1054	substrate 3367 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2A6 543	substrate 3367 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2B6 664	substrate 3367 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2C19 991	substrate 3367 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2E1 667	substrate 3367 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP3A5 395	substrate 3367 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11368292/ Page: 14.0	no	unknown (co-administration study) Comment: Coadministration with cyclocporine resulted in 3.1-fold increase in AUC; however, cannot be explained through these mechanisms, since neither pravastatin nor fluvastatin has been shown to be a substrate for either P-gp or CYP3A4 Sources: https://pubmed.ncbi.nlm.nih.gov/11368292/ Page: 14.0
OATP1B3 350	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17470528/	yes
OATP2B1 104	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17470528/	yes
OATP1B1 406	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/17470528/	yes	unlikely (co-administration study) Comment: coadministered with rifampin. See https://pubmed.ncbi.nlm.nih.gov/29768081/. Pharmacogenomic study also performed. Not significant: see https://www.lipidjournal.com/article/S1933-2874(14)00072-5/pdf Sources: https://pubmed.ncbi.nlm.nih.gov/17470528/
BCRP 561	substrate 3367 Sources: https://www.jpharmsci.org/article/S0022-3549(16)30083-1/pdf	yes	yes (pharmacogenomic study) Comment: AUC of drug increased by 72% Sources: https://www.jpharmsci.org/article/S0022-3549(16)30083-1/pdf

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:38561	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:38561
ChemicalBook	CB03386396	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB03386396
MolPort	MolPort-006-167-704	https://www.molport.com/shop/molecule-link/MolPort-006-167-704
ZINC	ZINC000001530639	http://zinc15.docking.org/substances/ZINC000001530639
eMolecules	10141252	https://www.emolecules.com/cgi-bin/more?vid=10141252

PubMed

Title	Date	PubMed
Synthesis and biological activity of new HMG-CoA reductase inhibitors. 3. Lactones of 6-phenoxy-3,5-dihydroxyhexanoic acids.	1991 Oct	1656041
HMG-CoA reductase inhibitors: design, synthesis, and biological activity of tetrahydroindazole-substituted 3,5-dihydroxy-6-heptenoic acid sodium salts.	1993 Nov 12	8246237
Fluvastatin in combination with other lipid-lowering agents.	1994 Dec	19496270
Treatment of primary hypercholesterolemia: fluvastatin versus bezafibrate.	1994 Jun 6	8017468
Efficacy and safety of a combination fluvastatin-bezafibrate treatment for familial hypercholesterolemia: comparative analysis with a fluvastatin-cholestyramine combination.	1994 May	8192170
Efficacy and safety of triple therapy (fluvastatin-bezafibrate-cholestyramine) for severe familial hypercholesterolemia.	1995 Jul 13	7604807
Currently available hypolipidaemic drugs and future therapeutic developments.	1995 Oct	8593127
Effect of fluvastatin or bezafibrate on the distribution of high density lipoprotein subpopulations in patients with familial hypercholesterolemia.	1996 Sep	8876936
Troglitazone upregulates LDL receptor activity in HepG2 cells.	1998 Aug	9703316
Postural hypotension induced by paroxetine.	1998 Feb 21	9518913
[Cardiology in 1997].	1998 Oct 5	9818470
Effect of 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors (statins) on tissue paraoxonase 1 and plasma platelet activating factor acetylhydrolase activities.	2004 Jan	14668577
Regional intestinal absorption and biliary excretion of fluvastatin in the rat: possible involvement of mrp2.	2004 Sep-Oct	16026004
Expression of serum and glucocorticoid-inducible kinase1 in diabetic rats and its modulation by fluvastatin.	2005	16696316
In vitro and pharmacophore-based discovery of novel hPEPT1 inhibitors.	2005 Apr	15846457
Effect of atorvastatin and fluvastatin on the metabolism of midazolam by cytochrome P450 in vitro.	2005 Aug	16029222
Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin.	2005 Aug	15901796
[Fluvastatin-induced dermatomyositis].	2005 Dec	16446645
Identification of HMG-CoA reductase inhibitors as activators for human, mouse and rat constitutive androstane receptor.	2005 Jul	15802384
Immediate effects of fluvastain on circulating soluble endothelial protein C and free tissue factor pathway inhibitor in acute coronary syndromes.	2005 May	16142594
Prediction of CYP2C9-mediated drug-drug interactions: a comparison using data from recombinant enzymes and human hepatocytes.	2005 Nov	16081671
Focal seizures after treatment with fluvastatin in a patient with a history of catastrophic antiphospholipid syndrome.	2005 Nov 15	16111706
Human hepatobiliary transport of organic anions analyzed by quadruple-transfected cells.	2005 Oct	16046661
Evaluation of the anti-HIV activity of statins.	2005 Oct 14	16184043
Binding thermodynamics of statins to HMG-CoA reductase.	2005 Sep 6	16128575
Effects of chronic treatment with statins and fenofibrate on rat skeletal muscle: a biochemical, histological and electrophysiological study.	2006 Dec	17031388
Muscle symptoms associated with statins: a series of twenty patients.	2006 Jan	16433891
Effect of low-density lipoprotein cholesterol on angiotensin II sensitivity: a randomized trial with fluvastatin.	2006 Jun	16618834
Fluvastatin ameliorates podocyte injury in proteinuric rats via modulation of excessive Rho signaling.	2006 Mar	16452496
Chiral evaluation of fluvastatin in human plasma by high-performance liquid chromatography electrospray mass spectrometry.	2006 Mar 7	16480934
Comprehensive analysis of the effects of ordinary nutrients on hepatitis C virus RNA replication in cell culture.	2007 Jun	17420205
Inhibitors of the mevalonate pathway as potential therapeutic agents in multiple myeloma.	2007 Mar	16996129
Cardioprotective effect of fluvastatin on isoproterenol-induced myocardial infarction in rat.	2008 May 31	18384769
Application of a 3,3-diphenylpentane skeleton as a multi-template for creation of HMG-CoA reductase inhibitors.	2009 Aug 1	19502059
Enantioselectivity in the pharmacokinetic interaction between fluvastatin and lercanidipine in healthy volunteers.	2009 Feb	19033449
Pretreatment with statin attenuates the cardiotoxicity of Doxorubicin in mice.	2009 Jan 15	19147586
Roles of different CYP enzymes in the formation of specific fluvastatin metabolites by human liver microsomes.	2009 Nov	19663817
Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development.	2010 Dec	20829430
In vitro interactions between primycin and different statins in their effects against some clinically important fungi.	2010 Feb	19875509
A gene score of nine LDL and HDL regulating genes is associated with fluvastatin-induced cholesterol changes in women.	2010 Mar	19773416
Effect of an antimicrobial agent on atherosclerotic plaques: assessment of metalloproteinase activity by molecular imaging.	2010 Mar 23	20298932
Effects of add-on fluvastatin therapy in patients with chronic proteinuric nephropathy on dual renin-angiotensin system blockade: the ESPLANADE trial.	2010 Nov	20671225
The phototoxicity of fluvastatin, an HMG-CoA reductase inhibitor, is mediated by the formation of a benzocarbazole-like photoproduct.	2010 Nov	20668001
Identification of old drugs as potential inhibitors of HIV-1 integrase - human LEDGF/p75 interaction via molecular docking.	2012 Dec	22733274
Detection of statin cytotoxicity is increased in cells expressing the OATP1B1 transporter.	2013 Jul	23564645
ATP-dependent transport of statins by human and rat MRP2/Mrp2.	2013 Jun 1	23562342
Statin-induced inhibition of breast cancer proliferation and invasion involves attenuation of iron transport: intermediacy of nitric oxide and antioxidant defence mechanisms.	2014 Aug	24964743
Statins alter the hepatobiliary transport of unconjugated and conjugated bilirubin in sandwich-cultured rat hepatocytes.	2014 Sep	24909372
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.	2015 May 18	25811541
Drug-Induced Acute Liver Injury Within 12 Hours After Fluvastatin Therapy.	2016 Jan-Feb	24451297

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Hyperlipidemia Immediate Release Capsules: -Low-density lipoprotein cholesterol (LDL-C) reduction to a goal of 25% or greater: Initial dose of 40 mg orally once a day in the evening or 40 mg orally twice a day -LDL-C reduction to a goal of less than 25%: Initial dose of 20 mg orally once a day -Maintenance dose: 20 mg to 80 mg per day Usual Adult Dose for Hyperlipoproteinemia Type IIa (Elevated LDL) Immediate Release Capsules: -Low-density lipoprotein cholesterol (LDL-C) reduction to a goal of 25% or greater: Initial dose of 40 mg orally once a day in the evening or 40 mg orally twice a day -LDL-C reduction to a goal of less than 25%: Initial dose of 20 mg orally once a day -Maintenance dose: 20 mg to 80 mg per day

Route of Administration: Oral

In Vitro Use Guide

Fluvastatin markedly inhibits the formation of thiobarbituric acid reactive substances in iron (II)-supported peroxidation of liposomes with IC50 of 12 uM. Fluvastatin ranging from 1 uM to 100 uM inhibits peroxyl radical-mediated peroxidation of liposomes induced by water-soluble and lipid-soluble radical generators, 2,2'-azobis (2-amidinopropane) dihydro-chloride and 2,2'-azobis (2,4-dimethylvaleronitrile), respectively.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 05:15:17 GMT 2023` Edited by `admin` on `Sat Dec 16 05:15:17 GMT 2023`
Record UNII	PYF7O1FV7F
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FLUVASTATIN SODIUM

Official Name

English

6-HEPTENOIC ACID, 7-(3-(4-FLUOROPHENYL)-1-(1-METHYLETHYL)-1H-INDOL-2-YL)-3,5-DIHYDROXY-, MONOSODIUM SALT, (R*,S*-(E))-(±)-

Common Name

English

LIPAXAN

Brand Name

English

FRACTAL

Brand Name

English

FLUVASTATIN SODIUM SALT [MI]

Common Name

English

CANEF

Brand Name

English

LESCOL

Brand Name

English

SODIUM (±)-(3R*,5S*,6E)-7-(3-(P-FLUOROPHENYL)-1-ISOPROPYLINDOL-2-YL)-3,5-DIHYDROXY-6-HEPTENOATE

Common Name

English

FLUINDOSTATIN

Common Name

English

VASTIN

Brand Name

English

LOCOL

Brand Name

English

XU 62-320

Code

English

CRANOC

Brand Name

English

XU-62-320

Code

English

FLUVASTATIN SODIUM [ORANGE BOOK]

Common Name

English

FLUVASTATIN SODIUM [MART.]

Common Name

English

FLUVASTATIN SODIUM [USP MONOGRAPH]

Common Name

English

LOCHOL

Brand Name

English

FLUVASTATIN SODIUM [JAN]

Common Name

English

FLUVASTATIN SODIUM [EP MONOGRAPH]

Common Name

English

FLUVASTATIN SODIUM [USP IMPURITY]

Common Name

English

FLUVASTATIN SODIUM [USP-RS]

Common Name

English

PRIMEXIN

Brand Name

English

FLUVASTATIN SODIUM SALT

Common Name

English

FLUVASTATIN SODIUM [VANDF]

Common Name

English

Fluvastatin sodium [WHO-DD]

Common Name

English

FLUVASTATIN SODIUM [USAN]

Common Name

English

ALMASTATIN

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1655