Details of the Drug

General Information of Drug (ID: DMJSBT6)

Drug Name

SILODOSIN

Synonyms

Silodosin; 160970-54-7; Rapaflo; Urief; Silodyx; Urorec; KMD-3213; Silodosin-d6; UNII-CUZ39LUY82; KMD 3213; KAD 3213; CUZ39LUY82; CHEMBL24778; KAD-3213; (R)-1-(3-hydroxypropyl)-5-(2-((2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl)amino)propyl)indoline-7-carboxamide; 1-(3-hydroxypropyl)-5-[(2R)-2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethylamino]propyl]-2,3-dihydroindole-7-carboxamide; 160970-64-9; Q-102517; Rapflo

Indication

Disease Entry	ICD 11	Status	REF
Benign prostatic hyperplasia	GA90	Approved	[1]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

495.5

Logarithm of the Partition Coefficient (xlogp)

3.6

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 373.4 +/- 164.94 mcgh/L [2]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 61.6 +/- 27.54 mcg/L [2]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 2.6 +/- 0.9 h [2]
Bioavailability: The bioavailability of drug is 32% [2]
Clearance: The clearance of drug is 10 L/h [2]
Elimination: About 33.5% of the dose was recovered in urine and 54.9% was recovered in feces [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 13.3 +/- 8.07 hours [2]
Metabolism: The drug is metabolized via the direct glucuronide conjugation mediated by UDP-glucuronosyltransferase 2B7 (UGT2B7) [2]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.2306 micromolar/kg/day [3]
Unbound Fraction: The unbound fraction of drug in plasma is 0.05% [4]
Vd: The volume of distribution (Vd) of drug is 49.5 L [2]

Chemical Identifiers

Formula: C25H32F3N3O4
IUPAC Name: 1-(3-hydroxypropyl)-5-[(2R)-2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethylamino]propyl]-2,3-dihydroindole-7-carboxamide
Canonical SMILES: C[C@H](CC1=CC2=C(C(=C1)C(=O)N)N(CC2)CCCO)NCCOC3=CC=CC=C3OCC(F)(F)F
InChI: InChI=1S/C25H32F3N3O4/c1-17(30-8-12-34-21-5-2-3-6-22(21)35-16-25(26,27)28)13-18-14-19-7-10-31(9-4-11-32)23(19)20(15-18)24(29)33/h2-3,5-6,14-15,17,30,32H,4,7-13,16H2,1H3,(H2,29,33)/t17-/m1/s1
InChIKey: PNCPYILNMDWPEY-QGZVFWFLSA-N

Cross-matching ID

PubChem CID: 5312125
ChEBI ID: CHEBI:135929
CAS Number: 160970-54-7
DrugBank ID: DB06207
TTD ID: D0U0VU
VARIDT ID: DR00285
INTEDE ID: DR1482
ACDINA ID: D01426

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor alpha-1A (ADRA1A)	TTNGILX	ADA1A_HUMAN	Inhibitor	[5]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Multidrug resistance protein 3 (ABCB4)	DTZRMK5	MDR3_HUMAN	Substrate	[6]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[8]
UDP-glucuronosyltransferase 2B7 (UGT2B7)_{Main DME}	DEB3CV1	UD2B7_HUMAN	Substrate	[9]
Alcohol dehydrogenase class-I alpha (ADH1A)	DEE5M8O	ADH1A_HUMAN	Substrate	[9]
Aldehyde dehydrogenase 2 (ALDH2)	DEWYTJB	ALDH2_HUMAN	Substrate	[9]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Protein Interaction/Cellular Processes	[10]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Benign prostatic hyperplasia

ICD Disease Classification

GA90

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Adrenergic receptor alpha-1A (ADRA1A)	DTT	ADRA1A	9.43E-01	-0.03	-0.25
Multidrug resistance protein 3 (ABCB4)	DTP	MDR3	9.66E-01	-6.64E-02	-5.69E-01
P-glycoprotein 1 (ABCB1)	DTP	P-GP	7.83E-01	4.69E-02	1.89E-01
Aldehyde dehydrogenase 2 (ALDH2)	DME	ALDH2	7.27E-01	3.28E-02	1.84E-01
Alcohol dehydrogenase class-I alpha (ADH1A)	DME	ADH1A	3.67E-01	4.99E-02	2.32E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	6.06E-01	-2.42E-02	-1.64E-01

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from SILODOSIN (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Silodosin caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[11]
Midostaurin	DMI6E0R	Moderate	Decreased clearance of Silodosin due to the transporter inhibition by Midostaurin.	Acute myeloid leukaemia [2A60]	[12]
Gilteritinib	DMTI0ZO	Moderate	Decreased clearance of Silodosin due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[11]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Silodosin caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[11]
Erdafitinib	DMI782S	Moderate	Decreased clearance of Silodosin due to the transporter inhibition by Erdafitinib.	Bladder cancer [2C94]	[13]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Silodosin caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[11]
Tucatinib	DMBESUA	Major	Decreased metabolism of Silodosin caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[11]
Palbociclib	DMD7L94	Moderate	Decreased metabolism of Silodosin caused by Palbociclib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[14]
Lumacaftor	DMCLWDJ	Moderate	Accelerated clearance of Silodosin due to the transporter induction by Lumacaftor.	Cystic fibrosis [CA25]	[11]
Ivacaftor	DMZC1HS	Moderate	Decreased metabolism of Silodosin caused by Ivacaftor mediated inhibition of CYP450 enzyme.	Cystic fibrosis [CA25]	[14]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of Silodosin caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[14]
OPC-34712	DMHG57U	Moderate	Additive hypotensive effects by the combination of Silodosin and OPC-34712.	Depression [6A70-6A7Z]	[15]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of Silodosin caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[11]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Silodosin caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[11]
Levobetaxolol	DMSREPX	Moderate	Additive hypotensive effects by the combination of Silodosin and Levobetaxolol.	Glaucoma [9C61]	[16]
Boceprevir	DMBSHMF	Major	Decreased metabolism of Silodosin caused by Boceprevir mediated inhibition of CYP450 enzyme.	Hepatitis virus infection [1E50-1E51]	[11]
GS-5885	DMSL3DX	Moderate	Decreased clearance of Silodosin due to the transporter inhibition by GS-5885.	Hepatitis virus infection [1E50-1E51]	[17]
Cobicistat	DM6L4H2	Major	Decreased metabolism of Silodosin caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[11]
Etravirine	DMGV8QU	Moderate	Increased metabolism of Silodosin caused by Etravirine mediated induction of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[11]
BMS-201038	DMQTAGO	Moderate	Decreased clearance of Silodosin due to the transporter inhibition by BMS-201038.	Hyper-lipoproteinaemia [5C80]	[18]
Tolvaptan	DMIWFRL	Moderate	Decreased clearance of Silodosin due to the transporter inhibition by Tolvaptan.	Hypo-osmolality/hyponatraemia [5C72]	[11]
Lesinurad	DMUR64T	Moderate	Increased metabolism of Silodosin caused by Lesinurad mediated induction of CYP450 enzyme.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[11]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Silodosin caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[14]
Suvorexant	DM0E6S3	Moderate	Decreased metabolism of Silodosin caused by Suvorexant mediated inhibition of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[14]
Glycerol phenylbutyrate	DMDGRQO	Moderate	Increased metabolism of Silodosin caused by Glycerol phenylbutyrate mediated induction of CYP450 enzyme.	Liver disease [DB90-DB9Z]	[11]
Crizotinib	DM4F29C	Moderate	Decreased metabolism of Silodosin caused by Crizotinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[14]
Ceritinib	DMB920Z	Major	Decreased metabolism of Silodosin caused by Ceritinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[11]
PF-06463922	DMKM7EW	Moderate	Accelerated clearance of Silodosin due to the transporter induction by PF-06463922.	Lung cancer [2C25]	[11]
Capmatinib	DMYCXKL	Moderate	Decreased clearance of Silodosin due to the transporter inhibition by Capmatinib.	Lung cancer [2C25]	[19]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of Silodosin caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[14]
Idelalisib	DM602WT	Major	Decreased metabolism of Silodosin caused by Idelalisib mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[11]
Ibrutinib	DMHZCPO	Moderate	Decreased clearance of Silodosin due to the transporter inhibition by Ibrutinib.	Mature B-cell lymphoma [2A85]	[12]
Vemurafenib	DM62UG5	Moderate	Increased metabolism of Silodosin caused by Vemurafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[11]
Dabrafenib	DMX6OE3	Moderate	Increased metabolism of Silodosin caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[12]
Lasmiditan	DMXLVDT	Moderate	Decreased clearance of Silodosin due to the transporter inhibition by Lasmiditan.	Migraine [8A80]	[20]
Ozanimod	DMT6AM2	Moderate	Additive hypotensive effects by the combination of Silodosin and Ozanimod.	Multiple sclerosis [8A40]	[21]
Rolapitant	DM8XP26	Moderate	Decreased clearance of Silodosin due to the transporter inhibition by Rolapitant.	Nausea/vomiting [MD90]	[22]
Netupitant	DMEKAYI	Moderate	Decreased metabolism of Silodosin caused by Netupitant mediated inhibition of CYP450 enzyme.	Nausea/vomiting [MD90]	[14]
Entrectinib	DMMPTLH	Moderate	Decreased metabolism of Silodosin caused by Entrectinib mediated inhibition of CYP450 enzyme.	Non-small cell lung cancer [2C25]	[14]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Silodosin caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[14]
Safinamide	DM0YWJC	Moderate	Additive hypotensive effects by the combination of Silodosin and Safinamide.	Parkinsonism [8A00]	[21]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Silodosin caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[23]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Silodosin caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[24]
Lonafarnib	DMGM2Z6	Major	Decreased metabolism of Silodosin caused by Lonafarnib mediated inhibition of CYP450 enzyme.	Premature ageing appearance [LD2B]	[11]
Enzalutamide	DMGL19D	Moderate	Increased metabolism of Silodosin caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[11]
Amisulpride	DMSJVAM	Moderate	Additive hypotensive effects by the combination of Silodosin and Amisulpride.	Schizophrenia [6A20]	[15]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of Silodosin caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[14]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Silodosin caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[11]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Silodosin caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[14]
Armodafinil	DMGB035	Moderate	Increased metabolism of Silodosin caused by Armodafinil mediated induction of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[11]
LEE011	DMMX75K	Moderate	Decreased metabolism of Silodosin caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[14]
Pitolisant	DM8RFNJ	Moderate	Increased metabolism of Silodosin caused by Pitolisant mediated induction of CYP450 enzyme.	Somnolence [MG42]	[11]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Silodosin caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[25]
Brilinta	DMBR01X	Moderate	Decreased metabolism of Silodosin caused by Brilinta mediated inhibition of CYP450 enzyme.	Thrombosis [DB61-GB90]	[14]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Gelatin	E00630	Not Available	Other agent
Magnesium stearate	E00208	11177	lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Acid blue 9 aluminum lake	E00583	56841154	Colorant
Colcothar yellow	E00436	518696	Colorant
Pregelatinized starch	E00674	Not Available	Binding agent; Diluent; Disintegrant
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Silodosin 8mg capsule	8mg	Capsule	Oral
Silodosin 4mg capsule	4mg	Capsule	Oral

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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: 493).
2	FDA Approved Drug Products: RAPAFLO (silodosin) Capsule for oral use
3	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
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	Pharmacophore identification of alpha(1A)-adrenoceptor antagonists. Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.
6	Pharmacokinetics and disposition of silodosin (KMD-3213)]. Yakugaku Zasshi. 2006 Mar;126 Spec no.:237-45.
7	The influence of UGT2B7, UGT1A8, MDR1, ALDH, ADH, CYP3A4 and CYP3A5 genetic polymorphisms on the pharmacokinetics of silodosin in healthy Chinese volunteers. Drug Metab Pharmacokinet. 2013;28(3):239-43.
8	Silodosin for benign prostatic hyperplasia. Ann Pharmacother. 2010 Feb;44(2):302-10.
9	Pharmacokinetics and disposition of silodosin (KMD-3213). Yakugaku Zasshi. 2006 Mar;126 Spec no.:237-45.
10	Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. Cardiovasc Res. 2004 Sep 1;63(4):662-72. doi: 10.1016/j.cardiores.2004.05.014.
11	Cerner Multum, Inc. "Australian Product Information.".
12	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
13	Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
14	Product Information. Rapaflo (silodosin). Watson Pharmaceuticals, Corona, CA.
15	Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30. [PMID: 7884028]
16	Chrysant SG "Experience with terazosin administered in combination with other antihypertensive agents." Am J Med 80 (1986): 55-61. [PMID: 2872808]
17	Product Information. Harvoni (ledipasvir-sofosbuvir). Gilead Sciences, Foster City, CA.
18	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
19	Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
20	Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
21	Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]
22	Product Information. Varubi (rolapitant). Tesaro Inc., Waltham, MA.
23	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
24	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
25	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.