Saquinavir

Summary

Saquinavir (CHEMBL114) is an approved small-molecule HIV protease inhibitor (ATC J05AE01) targeting ZC3H14; indicated across 6 conditions including hiv infectious disease and viral infectious disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: J05AE01
• Targets: 1 (ZC3H14)
• Indications: 6 conditions
• Clinical trials: 65
• Chemistry: 670.8 Da · C38H50N6O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL114
Name	Saquinavir
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	441243
ChEBI	CHEBI:63621
ATC	J05AE01
Molecular formula	C38H50N6O5
Molecular weight	670.8
InChIKey	QWAXKHKRTORLEM-UGJKXSETSA-N

SMILES: CC(C)(C)NC(=O)[C@@H]1C[C@@H]2CCCC[C@@H]2CN1C[C@H]([C@H](CC3=CC=CC=C3)NC(=O)[C@H](CC(=O)N)NC(=O)C4=NC5=CC=CC=C5C=C4)O

IUPAC name: (2S)-N-[(2S,3R)-4-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-(quinoline-2-carbonylamino)butanediamide

ChEBI definition: An aspartic acid derivative obtained by formal condensation of the primary amino group of (2S,3R)-4-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)octahydroisoquinolin-2(1H)-yl]-3-hydroxy-1-phenylbutan-2-ylamine with the carboxy group of N2(-quinolin-2-ylcarbonyl)-L-asparagine. An inhibitor of HIV-1 protease.

Pharmacological roles (ChEBI): HIV protease inhibitor, antiviral drug.

Also known as: Fortovase, Saquinavir, Saquinavirum, SCH-52852, saquinavir, SID49666064, SAQUINAVIR, SID50105601, C0088744

Parent form; salt/anhydrous children: CHEMBL282042

Patent coverage: 10,093 distinct patent families (39,899 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 39,468 (99%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
ZC3H14	zinc finger CCCH-type containing 14	Binding		0%	Q6PJT7

Broader ChEMBL bioactivity targets: 25 (assay-derived). Sample: Ferritin light chain, ATP-binding cassette sub-family C member 4, Chloroquine resistance transporter, 5-hydroxytryptamine receptor 2B, Thromboxane-A synthase, Vasopressin V1a receptor, Beta-lactamase, Solute carrier family 22 member 1, Voltage-gated L-type calcium channel, 5-hydroxytryptamine receptor 1A, D(2) dopamine receptor, Substance-K receptor, Mu-type opioid receptor, D(3) dopamine receptor, Delta-type opioid receptor, Kappa-type opioid receptor, Sodium-dependent dopamine transporter, Voltage-gated inwardly rectifying potassium channel KCNH2, 5-hydroxytryptamine receptor 1A, Cytochrome P450 3A4.

Bioactivity

ChEMBL activities: 26 potent at pChembl ≥ 5 of 47 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CYP3A4	6.77	Ki	170	nM	CHEMBL_ACT_6075220
CYP3A4	6.19	Ki	650	nM	CHEMBL_ACT_12163600
CYP3A4	5.82	IC50	1500	nM	CHEMBL_ACT_1166308
ABCB1	5.8	IC50	1600	nM	CHEMBL_ACT_1166311
CACNA1F	5.72	IC50	1900	nM	CHEMBL_ACT_15373355
TACR2	5.68	Ki	2071	nM	CHEMBL_ACT_7815858
TBXAS1	5.66	IC50	2182	nM	CHEMBL_ACT_7815861
OPRK1	5.61	AC50	2451	nM	CHEMBL_ACT_25129905
P19327	5.61	Ki	2442	nM	CHEMBL_ACT_7815832
OPRK1	5.56	Ki	2780	nM	CHEMBL_ACT_7815776
ABCB11	5.54	IC50	2900	nM	CHEMBL_ACT_18051980
ABCB11	5.54	IC50	2900	nM	CHEMBL_ACT_22396452
OPRM1	5.41	Ki	3907	nM	CHEMBL_ACT_7815778
P19327	5.37	IC50	4273	nM	CHEMBL_ACT_7815831
ABCB11	5.31	IC50	4900	nM	CHEMBL_ACT_18051770
ABCB11	5.31	IC50	4900	nM	CHEMBL_ACT_18129058
DRD3	5.28	Ki	5219	nM	CHEMBL_ACT_7813691
TACR2	5.21	IC50	6214	nM	CHEMBL_ACT_7815857
ABCB1	5.19	IC50	6500	nM	CHEMBL_ACT_11001807
OPRK1	5.16	IC50	6951	nM	CHEMBL_ACT_7815775
AVPR1A	5.15	Ki	7030	nM	CHEMBL_ACT_7815870
KCNH2	5.12	AC50	7543	nM	CHEMBL_ACT_25118606
Q63089	5.08	IC50	8260	nM	CHEMBL_ACT_11001866
OPRM1	5.02	IC50	9625	nM	CHEMBL_ACT_7815777
DRD2	5	AC50	10000	nM	CHEMBL_ACT_25140857
OPRD1	5	Ki	9930	nM	CHEMBL_ACT_7815774

Target pathways

Aggregated over 1 target gene(s): ZC3H14.

Dominant GO biological processes

GO term	Targets
spermatogenesis	1
cell differentiation	1
regulation of mRNA stability	1
mRNA stabilization	1
spliceosome-depend formation of circular RNA	1

Indications & clinical

Indications

2 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
HIV infectious disease	4	MONDO:0005109	EFO:0000764
viral infectious disease	4	MONDO:0005108	EFO:0000763

2 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
AIDS	3	MONDO:0012268	EFO:0000765
HIV-associated nephropathy	3	MONDO:0005798	EFO:0007313

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 65.

Phase distribution

Phase	Trials
PHASE2	24
PHASE3	11
PHASE1	11
PHASE4	8
Not specified	5
PHASE1/PHASE2	3
PHASE2/PHASE3	2
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00002229	PHASE4	COMPLETED	Safety and Effectiveness of Adding Saquinavir (FORTOVASE) in Soft Gel Capsule Form to an Anti-HIV Drug Combination in HIV-Infected Patients
NCT00002425	PHASE4	COMPLETED	The Safety and Effectiveness of Saquinavir Soft Gelatin Capsules Combined With Other Anti-HIV Drugs
NCT00050180	PHASE4	COMPLETED	Influence of the MDR1 Genotype on Blood Levels of Indinavir and Saquinavir in Healthy Volunteers
NCT00192660	PHASE4	COMPLETED	HIV Infection And Metabolic Abnormalities Protocol 1 (HAMA001)
NCT00379405	PHASE4	COMPLETED	Saquinavir/Ritonavir in Single Therapy as Maintenance Treatment
NCT00389402	PHASE4	COMPLETED	BASIC: Boosted Atazanavir or Saquinavir Induced Lipid Changes
NCT00438152	PHASE4	COMPLETED	Lopinavir Capsules to Kaletra or Invirase Tablets
NCT00717067	PHASE4	COMPLETED	Pharmacokinetics, Safety And Toleration Of Maraviroc Administered To Subjects With Various Degrees Of Renal Impaired And Normal Renal Function
NCT00002178	PHASE3	COMPLETED	A Phase IIIB Open-Label, Comparative Study to Evaluate Saquinavir Soft Gel Capsule (SGC) Treatment in Combination With Other Antiretrovirals in HIV-1 Infected Antiretroviral-Naive Patients
NCT00002334	PHASE3	COMPLETED	A Study of Zidovudine (AZT) Used Alone or in Combination With Other Anti-HIV Drugs in HIV-Infected Patients With Little or No Previous Treatment
NCT00002367	PHASE3	COMPLETED	A Study of Saquinavir Soft Gelatin Capsules Plus Zidovudine Plus Lamivudine in the Treatment of HIV-1 Infected Patients Who Have Never Taken Anti-HIV Drugs
NCT00002374	PHASE3	COMPLETED	A Study of Saquinavir Soft Gelatin Capsules Combined With Other Anti-HIV Drugs in HIV-1 Infected Patients
NCT00002378	PHASE3	COMPLETED	A Comparison of Three Anti-HIV Drug Combinations Containing Saquinavir Soft Gelatin Capsules Used in HIV-1 Infected Patients
NCT00002382	PHASE3	COMPLETED	A Study of Saquinavir Used Alone or in Combination With Other Anti-HIV Drugs in HIV-Infected Patients
NCT00002397	PHASE3	COMPLETED	A Study of Saquinavir Soft Gel Capsules (SGC) Used in Combination With Two Other Anti-HIV Drugs in Patients With HIV-Associated Kidney Disease
NCT00002447	PHASE3	COMPLETED	A Study to Compare Two Anti-HIV Drug Combinations
NCT00002448	PHASE3	COMPLETED	A Study to Compare the Effects of Two Anti-HIV Drug Combinations on the Immune Systems of HIV-Infected Patients
NCT00035932	PHASE3	COMPLETED	Atazanavir (BMS-232632) in Combination With Ritonavir or Saquinavir, and Lopinavir/Ritonavir, Each With Tenofovir and a Nucleoside in Subjects With HIV
NCT00038519	PHASE2/PHASE3	COMPLETED	Amprenavir/Ritonavir or Saquinavir/Ritonavir in HIV-Infected Subjects Following Failure With Kaletra as Their Second Protease Inhibitor
NCT00105079	PHASE3	COMPLETED	GEMINI Study - A Study of Saquinavir/Ritonavir in Treatment-Naive Patients With HIV-1 Infection
NCT00476983	PHASE2/PHASE3	WITHDRAWN	Pharmacokinetic and Efficacy of SQV/r 1500/100 Plus Tenofovir/Emtricitabine 300/200 mg
NCT00000848	PHASE2	COMPLETED	The Anti-HIV Effects of Saquinavir Soft Gelatin Capsules Versus Indinavir in Patients Who Have Used Saquinavir Hard Gelatin Capsules for One Year
NCT00000891	PHASE2	COMPLETED	Immunologic and Virologic Consequences of Long-Term Highly Active Antiretroviral Therapy (HAART) in Subjects With Moderately Advanced HIV-1 Disease: A Follow-Up Study to ACTG 315
NCT00000912	PHASE2	COMPLETED	A Study on Amprenavir in Combination With Other Anti-HIV Drugs in HIV-Positive Patients
NCT00000913	PHASE2	COMPLETED	A Study to Compare Two Anti-HIV Combination Therapies Each Containing Saquinavir in HIV-Positive Children
NCT00000918	PHASE2	COMPLETED	A Study to Compare The Ability of Different Anti-HIV Drugs to Decrease Viral Load After Nelfinavir (an Anti-HIV Drug)Treatment Failure
NCT00001040	PHASE2	COMPLETED	Comparison of Ro 31-8959 Plus Zidovudine (AZT) Versus AZT Plus Zalcitabine (ddC) Versus Ro 31-8959 Plus AZT Plus ddC
NCT00001087	PHASE2	COMPLETED	The Effectiveness of Nelfinavir and Efavirenz, Used Alone or Together, Combined With Other Anti-HIV Drugs in Patients Who Have Taken Anti-HIV Drugs
NCT00001094	PHASE2	WITHDRAWN	A Comparison of Nelfinavir Plus Saquinavir Plus Delavirdine or 3TC/ZDV Versus Nelfinavir Plus 3TC/ZDV in HIV-Infected Patients
NCT00002162	PHASE2	COMPLETED	A Randomized, Parallel Arm, Comparative, Open Label, Multicenter Study of the Activity and Safety of Two Formulations of Saquinavir in Combination With Other Antiretroviral Drugs
NCT00002184	PHASE2	COMPLETED	A Phase II, Stratified, Randomized, Double-Blind, Multi-Center Study of the Safety and Efficacy of Adefovir Dipivoxil (ADF) at Two Dose Levels in Triple Combination Therapies With Protease Inhibitors (PI) and Nucleoside Reverse Transcriptase Inhibitors (RTI) for the Treatment of HIV-Infected Patient
NCT00002190	PHASE2	COMPLETED	A Phase II Open-Label Exploratory Study of Saquinavir + Zidovudine + Lamivudine in HIV Infected Patients
NCT00002333	PHASE2	COMPLETED	A Study of Saquinavir and Zalcitabine, Used Alone and Together, in the Treatment of Advanced HIV Infection in Patients Who Stopped Taking or Who Cannot Take Zidovudine
NCT00002347	PHASE2	COMPLETED	The Safety and Effectiveness of Retrovir Plus HIVID Combined With Either Nevirapine or Invirase in the Treatment of HIV Infection
NCT00002440	PHASE2	COMPLETED	A Study of 1592U89 in Combination With Protease Inhibitors in HIV-Infected Patients Who Have Never Taken Anti-HIV Drugs
NCT00004584	PHASE2	COMPLETED	Safety and Effectiveness of a New Protease Inhibitor, BMS-232632, in HIV-Positive Patients Who Have Received Previous Treatment
NCT00038532	PHASE2	COMPLETED	Amprenavir/Ritonavir, Saquinavir/Ritonavir or Efavirenz in HIV-Infected Subjects Following Failure With Kaletra (ABT-378/Ritonavir) as Their First Protease Inhibitor Based HAART
NCT00046033	PHASE2	COMPLETED	Comparing Standard-Dose Versus Adjusted-Dose Lopinavir/Ritonavir Therapy in HIV-Infected Persons With Drug Resistance
NCT00056641	PHASE2	COMPLETED	Dual Boosted - Protease Inhibitor (PI) Pharmacokinetics (PK) Trial (Tipranavir / Ritonavir) in Highly Treatment-experienced HIV-1 Infected Patients
NCT00084058	PHASE1/PHASE2	COMPLETED	Safety of Saquinavir and High Doses of Lopinavir/Ritonavir in Children With HIV
NCT00102206	PHASE2	COMPLETED	A Comparison of Two Anti-HIV Drug Regimens for Youth Who Have Failed Prior Therapy
NCT00122603	PHASE2	COMPLETED	Dual Boosted Protease Inhibitor Regimens Without Any Additional Antiretroviral Therapy in HIV-1 Infected Patients (ANRS127)
NCT00145561	PHASE1/PHASE2	COMPLETED	The Pharmacokinetic Study of Saquinavir New Tablet Formulation in HIV-infected Pregnant Women.
NCT00400738	PHASE2	COMPLETED	The Pharmacokinetics of Double Boosted Protease Inhibitors in Antiretroviral-naive HIV-1 Infected Patients
NCT00477048	PHASE2	COMPLETED	Efficacy and Safety of SQV in Patients Who Have Chronic IDV Nephrotoxicity
NCT00622206	PHASE1/PHASE2	COMPLETED	Pharmacokinetics of Low Dose Ritonavir
NCT00623597	PHASE2	COMPLETED	A Study of Invirase (Saquinavir)/Ritonavir in HIV-Infected Infants and Children.
NCT02239835	PHASE2	TERMINATED	Tipranavir and Ritonavir vs. Saquinavir and Ritonavir Used With Two Nucleoside Reverse Transcriptase Inhibitors in Single Protease Inhibitor-experienced HIV-1 Patients
NCT00000906	PHASE1	COMPLETED	Interactions of HIV Protease Inhibitors and Methadone in HIV-Infected Patients
NCT00000920	PHASE1	COMPLETED	Fortovase (Saquinavir) Given With Low-Dose Ritonavir, Zidovudine, and Lamivudine to HIV-Positive Pregnant Women During and After Pregnancy and to Their Newborns
NCT00000941	PHASE1	COMPLETED	A Study on Possible Interactions Between Protease Inhibitors (Anti-HIV Drugs) and Drugs Which Lower the Level of Fat in Your Blood
NCT00001108	PHASE1	COMPLETED	A Study of the Safety and Effectiveness of Treating Advanced AIDS Patients Between Ages 4 and 22 With 7 Drugs, Some at Higher Than Usual Doses
NCT00002111	PHASE1	COMPLETED	A Dose-Escalating Study of Ro 31-8959 ( HIV Protease Inhibitor ) in Patients With HIV Disease.
NCT00002372	PHASE1	COMPLETED	A Study of 141W94 in Combination With Other Anti-HIV Drugs
NCT00002380	PHASE1	COMPLETED	The Safety and Effectiveness of Two Forms of Saquinavir Combined With Other Anti-HIV Drugs in HIV-Infected Infants and Children
NCT00002383	PHASE1	COMPLETED	A Comparison of Saquinavir Hard- and Soft-Gelatin Capsules in HIV-Infected Patients
NCT00307502	PHASE1	COMPLETED	Study to Determine the Pharmacokinetic Behavior of Antiretroviral Drugs in Patients Infected by HIV
NCT00435929	PHASE1	COMPLETED	A Study of Saquinavir/Ritonavir in Liver-Impaired Patients With HIV Infection.
NCT01638650	PHASE1	COMPLETED	A Study of Ritonavir-Boosted Invirase (Saquinavir) in Treatment-Naïve HIV-1 Infected Patients
NCT02023450	EARLY_PHASE1	UNKNOWN	Testing of HIV Protease Inhibitors to Suppress Inflammation and Improve Cardio Pulmonary Hemodynamics in Subjects With Pulmonary Arterial Hypertension
NCT00000892	Not specified	COMPLETED	A Study of Several Anti-HIV Drug Combinations in HIV-Infected Patients Who Have Used Indinavir
NCT00000898	Not specified	COMPLETED	The Effects of Staggered Dosing on Interactions Between Paired Combinations of Nelfinavir, Ritonavir, and Saquinavir
NCT00005762	Not specified	COMPLETED	Drug Interactions of Amprenavir and Efavirenz, in Combination With a Second Protease Inhibitor, in HIV-Negative Volunteers
NCT00051831	Not specified	COMPLETED	Effect of an Enfuvirtide-based Anti-HIV Drug Regimen on Latent HIV Reservoirs in Treatment Naive Adults
NCT00192608	Not specified	COMPLETED	A 48-Week, Randomised, Study to Describe the Pharmacokinetic Profile and Durability of Atazanavir-Saquinavir-Ritonavir Once Daily and Describe the Pharmacokinetic Profile of Saquinavir-Ritonavir Using Saquinavir 500mg Formulation: the ASK-500 Study

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).