Details of the Drug

General Information of Drug (ID: DMRADYL)

Drug Name

Pinacidil

Synonyms

Pinacidilum; P 1134; S 1230; P-154; Pinacidil (anhydrous); Pinacidilum [INN-Latin]; S-1230; N-Cyano-N'-4-pyridinyl-N''-(1,2,2-trimethylpropyl)guanidine; Guanidine, 2-cyano-3-(4-pyridyl)-1-(1,2,2-trimethylpropyl)-, monohydrate; Guanidine, N-cyano-N'-4-pyridinyl-N''-(1,2,2-trimethylpropyl)-, monohydrate; (+-)-Pinacidil; (+/-)-N-Cyano-N'-4-pyridinyl-N"-(1,2,2-trimethylpropyl)guanidine; (R,S)-Pinacidil; (inverted question mark)-N-Cyano-N'-4-pyridinyl-N''-(1,2,2-trimethylpropyl)-guanidine; 1-cyano-2-(3,3-dimethylbutan-2-yl)-3-pyridin-4-ylguanidine; 2-Cyano-3-(4-pyridinyl)-1-(1,2,2-trimethylpropyl)guanidine; 2-Cyano-3-(4-pyridyl)-1-(1,2,2-trimethylpropyl)guanidine monohydrate

Indication

Disease Entry	ICD 11	Status	REF
High blood pressure	BA00	Approved	[1], [2]

Therapeutic Class

Antihypertensive Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

245.32

Topological Polar Surface Area (xlogp)

2.7

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
Bioavailability: 57% of drug becomes completely available to its intended biological destination(s) [4]
Clearance: The drug present in the plasma can be removed from the body at the rate of 5.68 mL/min/kg [5]
Half-life: The concentration or amount of drug in body reduced by one-half in 2.5 hours [5]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 2.9115 micromolar/kg/day [6]
Unbound Fraction: The unbound fraction of drug in plasma is 0.6% [5]
Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.1 L/kg [5]

Chemical Identifiers

Formula: C13H19N5
IUPAC Name: 1-cyano-2-(3,3-dimethylbutan-2-yl)-3-pyridin-4-ylguanidine
Canonical SMILES: CC(C(C)(C)C)N=C(NC#N)NC1=CC=NC=C1
InChI: InChI=1S/C13H19N5/c1-10(13(2,3)4)17-12(16-9-14)18-11-5-7-15-8-6-11/h5-8,10H,1-4H3,(H2,15,16,17,18)
InChIKey: IVVNZDGDKPTYHK-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 4826
ChEBI ID: CHEBI:91706
CAS Number: 60560-33-0
DrugBank ID: DB06762
TTD ID: D02KMO
INTEDE ID: DR1292

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Potassium channel unspecific (KC)	TT1VOHK	NOUNIPROTAC	Modulator	[7]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[8]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2412).
2	FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 019456.
3	BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
4	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
5	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
7	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
8	Cytochrome P450 3A4-mediated oxidative conversion of a cyano to an amide group in the metabolism of pinacidil. Biochemistry. 2002 Feb 26;41(8):2712-8.
9	Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
10	Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
11	Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
12	Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
13	Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
14	Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
15	Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
16	The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
17	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
18	Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
19	2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
20	Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
21	Azimilide. Drugs. 2000 Feb;59(2):271-7; discussion 278-9.