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Economics

Properties

Spectra

Taxonomy

Saquinavir

Targets (1)Enzymes (6)Carriers (2)Transporters (9)Biointeractions (23)

Identification

Name

Saquinavir

Accession Number

DB01232 (APRD00623)

Type

Small Molecule

Groups

Approved, Investigational

Description

An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases. [PubChem]

Structure

Similar Structures

Synonyms

Saquinavir Mesylate
SQV

External IDs

RO 31-8959/000 / RO-31-8959/000 / SCH-52852

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Fortovase	Capsule, liquid filled	200 mg/1	Oral	Genentech, Inc.	1997-11-07	2012-04-18
Fortovase Roche	Capsule	200 mg	Oral	Hoffmann La Roche	1998-11-26	2007-03-06
Invirase	Capsule	200 mg	Oral	Roche Registration Gmb H	1996-10-04	Not applicable
Invirase	Capsule	200 mg/1	Oral	Genentech, Inc.	1995-12-06	Not applicable
Invirase	Tablet, film coated	500 mg/1	Oral	State of Florida DOH Central Pharmacy	2009-07-01	Not applicable
Invirase	Capsule	200 mg/1	Oral	Remedy Repack	2013-05-01	2013-05-02
Invirase	Tablet, film coated	500 mg	Oral	Roche Registration Gmb H	1996-10-04	Not applicable
Invirase	Tablet	500 mg	Oral	Hoffmann La Roche	2006-04-10	Not applicable
Invirase	Tablet, film coated	500 mg/1	Oral	Genentech, Inc.	2004-12-17	Not applicable
Invirase - Cap 200mg	Capsule	200 mg	Oral	Hoffmann La Roche	1996-12-31	Not applicable

International/Other Brands

Fortovase / ROC

Categories

UNII

L3JE09KZ2F

CAS number

127779-20-8

Weight

Average: 670.8408
Monoisotopic: 670.38426874

Chemical Formula

C₃₈H₅₀N₆O₅

InChI Key

QWAXKHKRTORLEM-UGJKXSETSA-N

InChI

InChI=1S/C38H50N6O5/c1-38(2,3)43-37(49)32-20-26-14-7-8-15-27(26)22-44(32)23-33(45)30(19-24-11-5-4-6-12-24)41-36(48)31(21-34(39)46)42-35(47)29-18-17-25-13-9-10-16-28(25)40-29/h4-6,9-13,16-18,26-27,30-33,45H,7-8,14-15,19-23H2,1-3H3,(H2,39,46)(H,41,48)(H,42,47)(H,43,49)/t26-,27+,30-,31-,32-,33+/m0/s1

IUPAC Name

(2S)-N-[(2S,3R)-4-[(3S,4aS,8aS)-3-(tert-butyl-C-hydroxycarbonimidoyl)-decahydroisoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-(quinolin-2-ylformamido)butanediimidic acid

SMILES

[H][C@@](O)(CN1C[C@@]2([H])CCCC[C@@]2([H])C[C@@]1([H])C(O)=NC(C)(C)C)[C@]([H])(CC1=CC=CC=C1)N=C(O)[C@]([H])(CC(O)=N)NC(=O)C1=NC2=CC=CC=C2C=C1

Pharmacology

Indication

For the treatment of HIV-1 with advanced immunodeficiency together with antiretroviral nucleoside analogues.

Associated Conditions

Infection, Human Immunodeficiency Virus I

Pharmacodynamics

Saquinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Saquinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.

Mechanism of action

Saquinavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.

Target	Actions	Organism
AHuman immunodeficiency virus type 1 protease	inhibitor	Human immunodeficiency virus 1

Absorption

Absolute bioavailability averages 4%

Volume of distribution

700 L

Protein binding

98%

Metabolism

Hepatic

Route of elimination

In vitro studies using human liver microsomes have shown that the metabolism of saquinavir is cytochrome P450 mediated with the specific isoenzyme, CYP3A4, responsible for more than 90% of the hepatic metabolism. Only 1% of saquinavir is excreted in the urine, so the impact of renal impairment on saquinavir elimination should be minimal.

Half life

Not Available

Clearance

1.14 L/h/kg [Healthy volunteers receiving IV doses of 6, 36, and 72 mg]

Toxicity

Probably experience pain in the throat

Affected organisms

Human Immunodeficiency Virus

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction
(R)-warfarin	The metabolism of (R)-warfarin can be decreased when combined with Saquinavir.
(S)-Warfarin	The metabolism of (S)-Warfarin can be decreased when combined with Saquinavir.
16-Bromoepiandrosterone	The serum concentration of 16-Bromoepiandrosterone can be increased when it is combined with Saquinavir.
19-norandrostenedione	The serum concentration of 19-norandrostenedione can be increased when it is combined with Saquinavir.
2,4-thiazolidinedione	The therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Saquinavir.
3,5-diiodothyropropionic acid	The metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Saquinavir.
4-hydroxycoumarin	The metabolism of 4-hydroxycoumarin can be decreased when combined with Saquinavir.
5-androstenedione	The serum concentration of 5-androstenedione can be increased when it is combined with Saquinavir.
5-androstenedione	The metabolism of 5-androstenedione can be decreased when combined with Saquinavir.
6-O-benzylguanine	The metabolism of 6-O-benzylguanine can be decreased when combined with Saquinavir.

Food Interactions

Take after a full meal.

References

Synthesis Reference

US5196438

General References

Forestier F, de Renty P, Peytavin G, Dohin E, Farinotti R, Mandelbrot L: Maternal-fetal transfer of saquinavir studied in the ex vivo placental perfusion model. Am J Obstet Gynecol. 2001 Jul;185(1):178-81. [PubMed:11483925]

External Links

KEGG Drug: D00429
PubChem Compound: 441243
PubChem Substance: 46508726
ChemSpider: 390016
BindingDB: 519
ChEBI: 63621
ChEMBL: CHEMBL114
Therapeutic Targets Database: DAP000171
PharmGKB: PA451305
HET: ROC
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Saquinavir

ATC Codes

J05AE01 — Saquinavir

AHFS Codes

08:18.08.08 — HIV Protease Inhibitors

PDB Entries

1c6z / 1fb7 / 1hxb / 2nmy / 2nmz / 2nnk / 2nnp / 3cyx / 3d1x / 3d1y …

show 17 more

FDA label

Download (362 KB)

MSDS

Download (15.8 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
0	Unknown Status	Treatment	Pulmonary Arterial Hypertension (PAH)	1
1	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	10
1	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections / Pregnancy	1
1, 2	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	3
2	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	22
2	Completed	Treatment	IDV Associated Nephrotoxicity	1
2	Completed	Treatment	Sarcomas	1
2	Terminated	Treatment	Human Immunodeficiency Virus (HIV) Infections	1
2	Withdrawn	Treatment	Human Immunodeficiency Virus (HIV) Infections	1
2, 3	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	3
3	Completed	Not Available	Directly Observed Therapy / Human Immunodeficiency Virus (HIV) Infections	1
3	Completed	Treatment	AIDS-Associated Nephropathy / Human Immunodeficiency Virus (HIV) Infections	1
3	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	10
4	Completed	Diagnostic	Cardiovascular Disease (CVD) / HIV-Associated Lipodystrophy Syndrome	1
4	Completed	Prevention	Human Immunodeficiency Virus (HIV) Infections	1
4	Completed	Treatment	Healthy Volunteers / Human Immunodeficiency Virus (HIV) Infections	1
4	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	5
Not Available	Completed	Prevention	Ischemia, Cerebral	1
Not Available	Completed	Treatment	Human Immunodeficiency Virus (HIV) Infections	4

Pharmacoeconomics

Manufacturers

Not Available

Packagers

A-S Medication Solutions LLC
F Hoffmann La Roche Ltd.
F Hoffmann-La Roche Ltd.
Pharmaceutical Utilization Management Program VA Inc.
Physicians Total Care Inc.
R.P. Scherer GmbH and Co. KG

Dosage forms

Form	Route	Strength
Capsule, liquid filled	Oral	200 mg/1
Capsule	Oral	200 mg/1
Tablet	Oral	500 mg
Tablet, film coated	Oral	500 mg/1
Tablet, film coated	Oral	500 mg
Capsule	Oral	200 mg

Prices

Unit description	Cost	Unit
Invirase 500 mg tablet	8.72USD	tablet
Invirase 200 mg capsule	3.87USD	capsule
Fortovase 200 mg capsule	1.46USD	capsule

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US5196438	No	1993-11-19	2010-11-19
CA2224125	No	2004-09-28	2016-06-04
CA2030433	No	1997-10-21	2010-11-21
US6352717	Yes	2000-05-16	2020-05-16
US6008228	Yes	1995-12-06	2015-12-06

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	349.84 °C	Not Available
water solubility	Insoluble	Not Available
logP	3.8	Not Available
Caco2 permeability	-6.26	ADME Research, USCD

Predicted Properties

Property	Value	Source
Water Solubility	0.00765 mg/mL	ALOGPS
logP	3.96	ALOGPS
logP	2.58	ChemAxon
logS	-4.9	ALOGPS
pKa (Strongest Acidic)	5.11	ChemAxon
pKa (Strongest Basic)	8.31	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	10	ChemAxon
Hydrogen Donor Count	6	ChemAxon
Polar Surface Area	174.72 Å²	ChemAxon
Rotatable Bond Count	13	ChemAxon
Refractivity	198.65 m³·mol^-1	ChemAxon
Polarizability	74.25 Å³	ChemAxon
Number of Rings	5	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.7774
Blood Brain Barrier	-	0.9949
Caco-2 permeable	-	0.8957
P-glycoprotein substrate	Substrate	0.9048
P-glycoprotein inhibitor I	Inhibitor	0.8563
P-glycoprotein inhibitor II	Inhibitor	0.5195
Renal organic cation transporter	Non-inhibitor	0.8612
CYP450 2C9 substrate	Non-substrate	0.8593
CYP450 2D6 substrate	Substrate	0.8918
CYP450 3A4 substrate	Substrate	0.7406
CYP450 1A2 substrate	Non-inhibitor	0.8729
CYP450 2C9 inhibitor	Non-inhibitor	0.7442
CYP450 2D6 inhibitor	Non-inhibitor	0.8536
CYP450 2C19 inhibitor	Non-inhibitor	0.7124
CYP450 3A4 inhibitor	Inhibitor	0.5219
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9053
Ames test	Non AMES toxic	0.8489
Carcinogenicity	Non-carcinogens	0.865
Biodegradation	Not ready biodegradable	1.0
Rat acute toxicity	2.6007 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9687
hERG inhibition (predictor II)	Inhibitor	0.8153

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Taxonomy

Description: This compound belongs to the class of organic compounds known as quinoline carboxamides. These are quinolines in which the quinoline ring system is substituted by one or more carboxamide groups.
Kingdom: Organic compounds
Super Class: Organoheterocyclic compounds
Class: Quinolines and derivatives
Sub Class: Quinoline carboxamides
Direct Parent: Quinoline carboxamides
Alternative Parents: Phenylbutylamines / Amphetamines and derivatives / Pyridinecarboxylic acids and derivatives / Piperidinecarboxamides / 2-heteroaryl carboxamides / Aralkylamines / Heteroaromatic compounds / Trialkylamines / Secondary carboxylic acid amides / Secondary alcohols
show 8 more
Substituents: Quinoline-2-carboxamide / Phenylbutylamine / Amphetamine or derivatives / 2-piperidinecarboxamide / Piperidinecarboxamide / Pyridine carboxylic acid or derivatives / 2-heteroaryl carboxamide / Aralkylamine / Monocyclic benzene moiety / Piperidine
show 26 more
Molecular Framework: Aromatic heteropolycyclic compounds
External Descriptors: quinolines, L-asparagine derivative (CHEBI:63621)

Targets

Details1. Human immunodeficiency virus type 1 protease

Kind: Protein
Organism: Human immunodeficiency virus 1
Pharmacological action: Yes
Actions: Inhibitor

General Function: Aspartic-type endopeptidase activity
Specific Function: Not Available
Gene Name: pol
Uniprot ID: Q72874
Uniprot Name: Pol polyprotein
Molecular Weight: 10778.7 Da

References

Wittayanarakul K, Hannongbua S, Feig M: Accurate prediction of protonation state as a prerequisite for reliable MM-PB(GB)SA binding free energy calculations of HIV-1 protease inhibitors. J Comput Chem. 2008 Apr 15;29(5):673-85. [PubMed:17849388]
Dandache S, Sevigny G, Yelle J, Stranix BR, Parkin N, Schapiro JM, Wainberg MA, Wu JJ: In vitro antiviral activity and cross-resistance profile of PL-100, a novel protease inhibitor of human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2007 Nov;51(11):4036-43. Epub 2007 Jul 16. [PubMed:17638694]
Dandache S, Coburn CA, Oliveira M, Allison TJ, Holloway MK, Wu JJ, Stranix BR, Panchal C, Wainberg MA, Vacca JP: PL-100, a novel HIV-1 protease inhibitor displaying a high genetic barrier to resistance: an in vitro selection study. J Med Virol. 2008 Dec;80(12):2053-63. doi: 10.1002/jmv.21329. [PubMed:19040279]
Rhee SY, Taylor J, Fessel WJ, Kaufman D, Towner W, Troia P, Ruane P, Hellinger J, Shirvani V, Zolopa A, Shafer RW: HIV-1 protease mutations and protease inhibitor cross-resistance. Antimicrob Agents Chemother. 2010 Oct;54(10):4253-61. doi: 10.1128/AAC.00574-10. Epub 2010 Jul 26. [PubMed:20660676]
Alcaro S, Artese A, Ceccherini-Silberstein F, Ortuso F, Perno CF, Sing T, Svicher V: Molecular dynamics and free energy studies on the wild-type and mutated HIV-1 protease complexed with four approved drugs: mechanism of binding and drug resistance. J Chem Inf Model. 2009 Jul;49(7):1751-61. doi: 10.1021/ci900012k. [PubMed:19537723]
Vella S, Lazzarin A, Carosi G, Sinicco A, Armignacco O, Angarano G, Andreoni M, Tambussi G, Chiodera A, Floridia M, Scaccabarozzi S, Facey K, Duncan I, Boudes P, Bragman K: A randomized controlled trial of a protease inhibitor (saquinavir) in combination with zidovudine in previously untreated patients with advanced HIV infection. Antivir Ther. 1996 Aug;1(3):129-40. [PubMed:11322246]
Hoetelmans RM, Meenhorst PL, Mulder JW, Burger DM, Koks CH, Beijnen JH: Clinical pharmacology of HIV protease inhibitors: focus on saquinavir, indinavir, and ritonavir. Pharm World Sci. 1997 Aug;19(4):159-75. [PubMed:9297727]

Enzymes

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	1500	N/A	N/A	12699389
Ki (nM)	170	N/A	N/A	16248836
Ki (nM)	650	N/A	N/A	22409598

Details1. Cytochrome P450 3A4

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Vitamin d3 25-hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name: CYP3A4
Uniprot ID: P08684
Uniprot Name: Cytochrome P450 3A4
Molecular Weight: 57342.67 Da

References

Zhou SF, Zhou ZW, Yang LP, Cai JP: 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. Epub 2009 Sep 1. [PubMed:19515014]
Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Ekins S, Bravi G, Wikel JH, Wrighton SA: Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33. [PubMed:10490933]
Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Details2. Cytochrome P450 3A5

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Oxygen binding
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP3A5
Uniprot ID: P20815
Uniprot Name: Cytochrome P450 3A5
Molecular Weight: 57108.065 Da

References

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Granfors MT, Wang JS, Kajosaari LI, Laitila J, Neuvonen PJ, Backman JT: Differential inhibition of cytochrome P450 3A4, 3A5 and 3A7 by five human immunodeficiency virus (HIV) protease inhibitors in vitro. Basic Clin Pharmacol Toxicol. 2006 Jan;98(1):79-85. doi: 10.1111/j.1742-7843.2006.pto_249.x. [PubMed:16433896]
Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Details3. Cytochrome P450 3A7

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Oxygen binding
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP3A7
Uniprot ID: P24462
Uniprot Name: Cytochrome P450 3A7
Molecular Weight: 57525.03 Da

References

Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Details4. Cholesterol side-chain cleavage enzyme, mitochondrial

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Substrate

General Function: Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, nad(p)h as one donor, and incorporation of one atom of oxygen
Specific Function: Catalyzes the side-chain cleavage reaction of cholesterol to pregnenolone.
Gene Name: CYP11A1
Uniprot ID: P05108
Uniprot Name: Cholesterol side-chain cleavage enzyme, mitochondrial
Molecular Weight: 60101.87 Da

References

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Details5. Cytochrome P450 2C8

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Steroid hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP2C8
Uniprot ID: P10632
Uniprot Name: Cytochrome P450 2C8
Molecular Weight: 55824.275 Da

References

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]

Details6. Cytochrome P450 2D6

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Steroid hydroxylase activity
Specific Function: Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name: CYP2D6
Uniprot ID: P10635
Uniprot Name: Cytochrome P450 2D6
Molecular Weight: 55768.94 Da

References

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
von Moltke LL, Greenblatt DJ, Duan SX, Daily JP, Harmatz JS, Shader RI: Inhibition of desipramine hydroxylation (Cytochrome P450-2D6) in vitro by quinidine and by viral protease inhibitors: relation to drug interactions in vivo. J Pharm Sci. 1998 Oct;87(10):1184-9. doi: 10.1021/js980197h. [PubMed:9758674]

Carriers

Details1. Alpha-1-acid glycoprotein 1

Kind: Protein
Organism: Human
Pharmacological action: Unknown

General Function: Not Available
Specific Function: Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name: ORM1
Uniprot ID: P02763
Uniprot Name: Alpha-1-acid glycoprotein 1
Molecular Weight: 23511.38 Da

References

Holladay JW, Dewey MJ, Michniak BB, Wiltshire H, Halberg DL, Weigl P, Liang Z, Halifax K, Lindup WE, Back DJ: Elevated alpha-1-acid glycoprotein reduces the volume of distribution and systemic clearance of saquinavir. Drug Metab Dispos. 2001 Mar;29(3):299-303. [PubMed:11181499]

Details2. Serum albumin

Kind: Protein
Organism: Human
Pharmacological action: Unknown

General Function: Toxic substance binding
Specific Function: Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name: ALB
Uniprot ID: P02768
Uniprot Name: Serum albumin
Molecular Weight: 69365.94 Da

References

Holladay JW, Dewey MJ, Michniak BB, Wiltshire H, Halberg DL, Weigl P, Liang Z, Halifax K, Lindup WE, Back DJ: Elevated alpha-1-acid glycoprotein reduces the volume of distribution and systemic clearance of saquinavir. Drug Metab Dispos. 2001 Mar;29(3):299-303. [PubMed:11181499]

Transporters

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	100000	N/A	N/A	17664327
IC 50 (nM)	12000	N/A	N/A	12699389
IC 50 (nM)	1600	N/A	N/A	12699389
IC 50 (nM)	6500	N/A	N/A	10820137

Details1. Multidrug resistance protein 1

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Substrate
Inhibitor
Inducer

General Function: Xenobiotic-transporting atpase activity
Specific Function: Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name: ABCB1
Uniprot ID: P08183
Uniprot Name: Multidrug resistance protein 1
Molecular Weight: 141477.255 Da

References

Perloff MD, von Moltke LL, Fahey JM, Daily JP, Greenblatt DJ: Induction of P-glycoprotein expression by HIV protease inhibitors in cell culture. AIDS. 2000 Jun 16;14(9):1287-9. [PubMed:10894301]
Choo EF, Leake B, Wandel C, Imamura H, Wood AJ, Wilkinson GR, Kim RB: Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab Dispos. 2000 Jun;28(6):655-60. [PubMed:10820137]
Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [PubMed:12699389]
Kim AE, Dintaman JM, Waddell DS, Silverman JA: Saquinavir, an HIV protease inhibitor, is transported by P-glycoprotein. J Pharmacol Exp Ther. 1998 Sep;286(3):1439-45. [PubMed:9732409]
Huisman MT, Smit JW, Wiltshire HR, Hoetelmans RM, Beijnen JH, Schinkel AH: P-glycoprotein limits oral availability, brain, and fetal penetration of saquinavir even with high doses of ritonavir. Mol Pharmacol. 2001 Apr;59(4):806-13. [PubMed:11259625]
Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. [PubMed:12948019]
Eagling VA, Profit L, Back DJ: Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-1 protease inhibitor saquinavir by grapefruit juice components. Br J Clin Pharmacol. 1999 Oct;48(4):543-52. [PubMed:10583025]
Collett A, Tanianis-Hughes J, Hallifax D, Warhurst G: Predicting P-glycoprotein effects on oral absorption: correlation of transport in Caco-2 with drug pharmacokinetics in wild-type and mdr1a(-/-) mice in vivo. Pharm Res. 2004 May;21(5):819-26. [PubMed:15180340]

Details2. Solute carrier family 22 member 1

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Secondary active organic cation transmembrane transporter activity
Specific Function: Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name: SLC22A1
Uniprot ID: O15245
Uniprot Name: Solute carrier family 22 member 1
Molecular Weight: 61153.345 Da

References

Zhang L, Gorset W, Washington CB, Blaschke TF, Kroetz DL, Giacomini KM: Interactions of HIV protease inhibitors with a human organic cation transporter in a mammalian expression system. Drug Metab Dispos. 2000 Mar;28(3):329-34. [PubMed:10681378]

Details3. Solute carrier organic anion transporter family member 1A2

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Sodium-independent organic anion transmembrane transporter activity
Specific Function: Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name: SLCO1A2
Uniprot ID: P46721
Uniprot Name: Solute carrier organic anion transporter family member 1A2
Molecular Weight: 74144.105 Da

References

Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB: OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos. 1999 Aug;27(8):866-71. [PubMed:10421612]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	19500	N/A	N/A	15007102

Details4. ATP-binding cassette sub-family G member 2

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Xenobiotic-transporting atpase activity
Specific Function: High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name: ABCG2
Uniprot ID: Q9UNQ0
Uniprot Name: ATP-binding cassette sub-family G member 2
Molecular Weight: 72313.47 Da

References

Gupta A, Zhang Y, Unadkat JD, Mao Q: HIV protease inhibitors are inhibitors but not substrates of the human breast cancer resistance protein (BCRP/ABCG2). J Pharmacol Exp Ther. 2004 Jul;310(1):334-41. Epub 2004 Mar 8. [PubMed:15007102]
Janneh O, Owen A, Chandler B, Hartkoorn RC, Hart CA, Bray PG, Ward SA, Back DJ, Khoo SH: Modulation of the intracellular accumulation of saquinavir in peripheral blood mononuclear cells by inhibitors of MRP1, MRP2, P-gp and BCRP. AIDS. 2005 Dec 2;19(18):2097-102. [PubMed:16284458]

Details5. Solute carrier organic anion transporter family member 1B1

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Sodium-independent organic anion transmembrane transporter activity
Specific Function: Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name: SLCO1B1
Uniprot ID: Q9Y6L6
Uniprot Name: Solute carrier organic anion transporter family member 1B1
Molecular Weight: 76447.99 Da

References

Tirona RG, Leake BF, Wolkoff AW, Kim RB: Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. J Pharmacol Exp Ther. 2003 Jan;304(1):223-8. [PubMed:12490595]

Details6. Multidrug resistance-associated protein 1

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Substrate

General Function: Transporter activity
Specific Function: Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name: ABCC1
Uniprot ID: P33527
Uniprot Name: Multidrug resistance-associated protein 1
Molecular Weight: 171589.5 Da

References

Williams GC, Liu A, Knipp G, Sinko PJ: Direct evidence that saquinavir is transported by multidrug resistance-associated protein (MRP1) and canalicular multispecific organic anion transporter (MRP2). Antimicrob Agents Chemother. 2002 Nov;46(11):3456-62. [PubMed:12384350]

Details7. Canalicular multispecific organic anion transporter 1

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Substrate

General Function: Organic anion transmembrane transporter activity
Specific Function: Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name: ABCC2
Uniprot ID: Q92887
Uniprot Name: Canalicular multispecific organic anion transporter 1
Molecular Weight: 174205.64 Da

References

Williams GC, Liu A, Knipp G, Sinko PJ: Direct evidence that saquinavir is transported by multidrug resistance-associated protein (MRP1) and canalicular multispecific organic anion transporter (MRP2). Antimicrob Agents Chemother. 2002 Nov;46(11):3456-62. [PubMed:12384350]
Huisman MT, Smit JW, Crommentuyn KM, Zelcer N, Wiltshire HR, Beijnen JH, Schinkel AH: Multidrug resistance protein 2 (MRP2) transports HIV protease inhibitors, and transport can be enhanced by other drugs. AIDS. 2002 Nov 22;16(17):2295-301. [PubMed:12441801]
Zelcer N, Huisman MT, Reid G, Wielinga P, Breedveld P, Kuil A, Knipscheer P, Schellens JH, Schinkel AH, Borst P: Evidence for two interacting ligand binding sites in human multidrug resistance protein 2 (ATP binding cassette C2). J Biol Chem. 2003 Jun 27;278(26):23538-44. Epub 2003 Apr 17. [PubMed:12702717]
Honda Y, Ushigome F, Koyabu N, Morimoto S, Shoyama Y, Uchiumi T, Kuwano M, Ohtani H, Sawada Y: Effects of grapefruit juice and orange juice components on P-glycoprotein- and MRP2-mediated drug efflux. Br J Pharmacol. 2004 Dec;143(7):856-64. Epub 2004 Oct 25. [PubMed:15504753]

Details8. Solute carrier organic anion transporter family member 2B1

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Sodium-independent organic anion transmembrane transporter activity
Specific Function: Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name: SLCO2B1
Uniprot ID: O94956
Uniprot Name: Solute carrier organic anion transporter family member 2B1
Molecular Weight: 76709.98 Da

References

Annaert P, Ye ZW, Stieger B, Augustijns P: Interaction of HIV protease inhibitors with OATP1B1, 1B3, and 2B1. Xenobiotica. 2010 Mar;40(3):163-76. doi: 10.3109/00498250903509375. [PubMed:20102298]

Details9. Bile salt export pump

Kind: Protein
Organism: Human
Pharmacological action: No
Actions: Substrate

General Function: Transporter activity
Specific Function: Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name: ABCB11
Uniprot ID: O95342
Uniprot Name: Bile salt export pump
Molecular Weight: 146405.83 Da

References

Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [PubMed:24014644]

Drug created on June 13, 2005 07:24 / Updated on October 18, 2018 16:30

Saquinavir

Identification

Structure for Saquinavir (DB01232)

Pharmacology

Interactions

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Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

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Enzymes

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Carriers

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Transporters

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