Repositioning Candidate Details
| Candidate ID: | R0121 |
| Source ID: | DB00425 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Zolpidem |
| Synonyms: | |
| Molecular Formula: | C19H21N3O |
| SMILES: | CN(C)C(=O)CC1=C(N=C2C=CC(C)=CN12)C1=CC=C(C)C=C1 |
| Structure: |
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| DrugBank Description: | Zolpidem, also known as _Ambien_, is a hypnotic drug that was initially approved by the FDA in 1992 [FDA label]. Zolpidem improves sleep in patients with insomnia. It is aimed for use in patients with difficulties initiating sleep. This drug decreases the time to fall asleep (sleep latency), increases the duration of sleep, and decreases the number of awakenings during sleep in patients with temporary (transient) insomnia. It is available in both immediate acting and extended release forms [FDA label], [F3802]. Its tolerability profile is favorable when administered according to the manufacturer’s instructions, with a low risk of drug withdrawal, drug dependence, and drug tolerance [A175426]. In addition, zolpidem improves sleep quality in patients suffering from chronic insomnia and can show mild muscle relaxant properties [L5584]. Research also shows that zolpidem is rapid and effective in restoring brain function for patients in a vegetative state following brain injury. This drug has the propensity to completely or partially reverse the abnormal metabolism of damaged brain cells after injury [L5584], [A175444]. |
| CAS Number: | 82626-48-0 |
| Molecular Weight: | 307.3895 |
| DrugBank Indication: | This drug is indicated for the short-term treatment of insomnia in adults characterized by difficulties with sleep initiation [FDA label]. |
| DrugBank Pharmacology: | **Effects on the central nervous system (CNS)** This drug has CNS depressant effects, which may include somnolence, decreased alertness, sedation, drowsiness, dizziness, and other changes in psychomotor function [FDA label]. Due to the above effects, the FDA has recommended an initial dose of zolpidem (immediate-acting) is a single dose of 5 mg for women and a single dose of 5 or 10 mg for men, immediately before bedtime with at least 7-8 hours remaining before the planned time of awakening [L5581]. Refer to product labeling for detailed information [F3802], [FDA label]. **Effects on memory** Controlled studies in adults using objective measures of memory demonstrated no significant evidence of next-day memory impairment after the administration of zolpidem. On the contrary, in a clinical study involving the administration of zolpidem doses of 10 and 20 mg, a marked reduction in a next-morning recall of information relayed to subjects during peak drug effect (90 minutes after dosing) was observed. These subjects experienced a condition known as _anterograde amnesia_. Subjective evidence from adverse event data has suggested that anterograde amnesia may occur after zolpidem administration, mainly at doses above 10 mg [FDA label]. **Effects on psychomotor function** This drug may cause decreased psychomotor performance. Additive psychomotor effects may occur with other drugs that cause depression of psychomotor function, including alcohol [FDA label]. Patients taking zolpidem should be cautioned against participating in hazardous activities or occupations requiring complete mental alertness or motor coordination, including operating machinery or driving a motor vehicle after ingesting the drug. Potential impairment of the performance of the above types of activities may also occur the day after zolpidem ingestion, especially at higher doses and ingestion of the extended-release form [FDA label], [F3802]. **Effects on insomnia and sleep stages** Evidence suggests that this drug is associated with minimal rebound insomnia. During clinical trials with patients using zolpidem on an ‘as-needed’ basis, zolpidem use resulted in global improvements in sleep [A175426]. Zolpidem has been demonstrated to decrease sleep latency (the time it takes to fall asleep) for up to 35 days in controlled clinical studies [FDA label]. In studies measuring the percentage of sleep time spent in each sleep stage, zolpidem has primarily been shown to preserve sleep stages. Sleep time spent in stages 3 and 4 (deep sleep) was measured as similar to placebo with only minor and inconsistent changes in REM (paradoxical) sleep at the recommended dose [FDA label]. **Next-day residual effects** In 2013, the FDA issued a statement warning that patients who take zolpidem extended-release (Ambien CR)―either 6.25 mg or 12.5 mg―should not drive or participate in other activities requiring full mental alertness the day after taking the drug, due to the fact that zolpidem concentrations can remain increased the next day, and impair the ability to perform these activities [L5581], [F3802]. Patients may decrease their risk of next-morning impairment by taking the lowest dose of their insomnia medicine that treats their symptoms, according to the FDA [L5590]. Specific dosing recommendations for both men and women are included in this statement [L5581]. This information is also available on product labeling [F3802], [FDA label]. **Rebound effects** There was no polysomnographic (objective) evidence of rebound insomnia at normal doses, in studies evaluating sleep on the nights following discontinuation of zolpidem tartrate. Subjective evidence of impaired sleep in the elderly on the first post-treatment night was observed at doses higher than the recommended 5mg dose for elderly patients [FDA label]. |
| DrugBank MoA: | Zolpidem, the active moiety of zolpidem tartrate, is a hypnotic substance with a chemical structure that is not related to the structure benzodiazepines, barbiturates, pyrrolopyrazines, pyrazolopyrimidines or other drugs exerting hypnotic effects. It interacts with a _GABA-BZ_ receptor complex and shares various pharmacological properties with the _benzodiazepine_ class of drugs [FDA label]. Subunit binding of the _GABAA_ receptor chloride channel macromolecular complex is thought to lead to the sedative, anticonvulsant, anxiolytic, and myorelaxant drug effects of zolpidem. The main regulatory site of the GABAA receptor complex can be found on its _alpha (α) subunit_ and is called the _benzodiazepine_ (BZ) or _omega (ω)_ receptor. At least three different subtypes of the (ω) receptor have been identified to this date [FDA label]. In contrast to benzodiazepine drugs, which are found to modulate all benzodiazepine receptor subtypes in a non-selective fashion, zolpidem binds the (BZ1) receptor specifically with a potent affinity for the alpha 1/alpha 5 subunits (in vitro) [FDA label]. More recent studies suggest that zolpidem binds primarily to the alpha 1, 2, and 3 subunits of the GABA receptor [A173896], [A10523], [A175567], and not the alpha 5 subunit. The (_BZ1_) receptor is found primarily on the Lamina IV of the brain sensorimotor cortical regions, substantia nigra (pars reticulata), cerebellum molecular layer, olfactory bulb, ventral thalamic complex, pons, inferior colliculus, and globus pallidus. Specific and selective binding of zolpidem on the (BZ1) receptor is not considered absolute, however, this binding could potentially explain the relative lack of myorelaxant and anticonvulsant activity in animal studies in addition to the preservation of deep sleep (stages 3 and 4) in human studies of zolpidem at hypnotic doses [FDA label]. |
| Targets: | Gamma-aminobutyric acid receptor subunit alpha-1; Gamma-aminobutyric acid receptor subunit alpha-2; Gamma-aminobutyric acid receptor subunit alpha-3; Gamma-aminobutyric acid receptor subunit gamma-2 |
| Inclusion Criteria: |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S01 | anti-apoptosis | Anti-inflammatory; Anti-apoptosis; Anti-oxidative stress; Anti-inflammatory; Anti-apoptosis; Anti-apoptosis; Anti-apoptosis; Anti-oxidative stress; Anti-inflammatory; inducing apoptosis in those cells; Anti-fibrosis; Anti-inflammatory; Anti-apoptosis; Anti-inflammatory; Anti-oxidative stress; Anti-apoptosis; Anti-apoptosis; Enhance lipid metabolism; Anti-oxidative stress; Anti-fibrosis; Anti-apoptosis; Anti-inflammatory; Anti-fibrosis; Anti-apoptosis; Anti-oxidative stress; Anti-inflammatory; Anti-fibrosis; Anti-apoptosis; Anti-oxidative stress; Anti-apoptosis; Anti-fibrosis; Anti-apoptosis | MAPK; caspase-3; Bcl-2; TNF-α; IL-1β; IL-6; podocin; nephrin; IL-1β; IL-6; TNF-α; HO-1; NF-κB; VDR; p38 MAPK; NF-κB; PPAR; AMPK; AMPK; NOX4; caspase-3; NOX4; ERK; Bcl-2; Nrf2; p53; Smad2/3; NOX4 | streptozotocin; Oleuropein; NS-398; iN/i-acetylcysteine; aminoguanidine; metformin; l-cysteine; Astragalus; Salvia miltrorrhiza; Polygala fallax Hemsl; compound Sanqi granules; metformin; Okadaic acid; miR-218 inhibitor; Gushen Jiedu capsule; Hirudin; Akebia saponin D; STZ; calcitriol; streptozocin; 1,25-dihydroxyvitamin D3; anisomycin; Echinacoside; PDTC; fenofibrate; miRNA antagomiR; dencichine; canagliflozin; isoprenaline; streptozotocin; recombinant human clusterin protein; Chloroquine; Amodiaquine; Streptozotocin; angiotensin II; calycosin; mitoquinone; ML385; Calcium dobesilate; FK506; SIS3; Forskolin; recombinant thrombomodulin | Details |
| S02 | anti-fibrosis | Anti-fibrosis; Anti-hypertensive; Anti-inflammatory; Anti-fibrosis; Anti-oxidative stress; Anti-fibrosis; Anti-inflammatory; Anti-fibrosis; anti-fibrosis; Anti-inflammatory; Anti-oxidative stress; Anti-fibrosis; Anti-fibrosis; Enhance lipid metabolism; Enhance lipid metabolism; Anti-inflammatory; Anti-fibrosis; Anti-oxidative stress; Anti-inflammatory; Anti-fibrosis; Improve insulin resistance; Enhance lipid metabolism; Regulating intestinal flora; Anti-fibrosis; Anti-fibrosis; Anti-inflammatory; Anti-apoptosis; Anti-hypertensive; Anti-inflammatory; Anti-fibrosis; Anti-oxidative stress; Anti-fibrosis; Anti-fibrosis; Enhance lipid metabolism; Improve insulin resistance; Anti-inflammatory; Anti-fibrosis; Enhance lipid metabolism; Anti-fibrosis; Anti-inflammatory; Anti-oxidative stress; Anti-fibrosis; Anti-apoptosis; Cell therapy; Anti-inflammatory; Anti-fibrosis; Anti-inflammatory; Anti-fibrosis; Anti-apoptosis; Cell therapy; Anti-fibrosis; Improve insulin resistance; Anti-oxidative stress; Anti-inflammatory; Anti-fibrosis; Anti-fibrosis; Anti-inflammatory; Anti-hypertensive; Anti-oxidative stress; Anti-inflammatory; Anti-fibrosis; Anti-apoptosis; Anti-fibrosis; Anti-inflammatory; Anti-oxidative stress; Anti-fibrosis; Anti-apoptosis; Enhance lipid metabolism; Anti-inflammatory; Anti-fibrosis; Anti-oxidative stress; Anti-inflammatory; Anti-oxidative stress; Anti-lipogenesis; Anti-fibrosis | HIF; FGF23; MAPK; Nrf2; HO-1; p38 MAPK; JNK; PPAR; FXR; Smad2/3; Smad2/3; TLR4; Smad2/3; Wnt/β-catenin; Smad2/3; Smad4; TGF-β; IL-1β; IL-6; TNF-α; ACE; Smad4; PKD1; p62; mTOR; TNF-α; TLR4; TGF-β; erythropoietin receptor; MMP-9; TLR4; IL-2; IL-24; IL-2; NOX4; MAPK; ACE; NF-κB; STAT3; JAK2; NOX4; NF-κB; Nrf2; SGLT2; HIF; Smad2/3; NF-κB; AMPK; mTOR; ERK; MAPK; AMPK; IL-6; IL-1β; TNF-α; TGF-β; EGF; RAGE; Wnt/β-catenin; AKT; AMPK; NOX4; caspase-3; NLRP3; NLRP3; NF-κB; Smad2/3; Smad2/3; p38 MAPK; p53 | riociguat; sGC stimulators; sGC activators; MRI-1867; JD5037; 1400W; HIF-PH inhibitors; paricalcitol; LNA-anti-miR-150; scrambled LNA; Ganoderic acid; GA-A; BML-111; ML385; traditional medicine; saikosaponin B2; miR-9-5p; cisplatin; CP; obeticholic acid (OCA; 6-ethyl chenodeoxycholic acid); tropifexor; nidufexor; mdivi-1; silibinin; lisinopril; MK-521; Adriamycin; 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione; NOX5 siRNA; ICG-001; IC-2; IC-2-506-1; IC-2-506-2; IC-2-506-3; IC-2-Ar-Cl; IC-2-OH; IC-2-OTBS; IC-2-F; Rehmannia glutinosa leaves total glycoside; glucose; glucosamine; streptozotocin; Low molecular weight fucoidan; protamine sulfate; propionate; Hirudin; Hsub2/subS; NO; Hsub2/subSxa0; xa0; NO; angiotensin-converting enzyme inhibitors; angiotensin II receptor blockers; N-acetyl-seryl-aspartyl-lysyl-proline; USC; Korean red ginseng; Panax ginseng C.A. Mey.; streptozotocin; dapagliflozin; losartan; Bisphosphonates; RIS; recombinant human soluble thrombomodulin; deacetylase inhibitors; Human recombinant erythropoietin; rEPO; Huangkui capsule; 1,25sub2/subDsub3/sub; Danggui-Shaoyao-San; IL-24; Jiawei Shuilu Erxiandan; Coptis; CH5451098; MRS1754; Retinoic acid; ACE inhibitors; ATsub1/sub receptor antagonists; N-acetyl-seryl-aspartyl-lysyl-proline; glycolysis inhibitors; prolyl oligopeptidase inhibitor S17092; imidapril; TA-606; Baicalin; β-Caryophyllene; dapagliflozin; streptozocin; fosinopril; valsartan; Chrysophanol; Plantamajoside; miR-101a-3p; miR-101; Am80; all-trans retinoic acid; Ginsenoside Rb1; rapamycin; Akt inhibitor; metformin; p38-MAPK inhibitor; ERK-MAPK inhibitor; psoralen; GLP-1RAs; liraglutide; XAV-939; streptozocin; TGF-x3b2; 1; dencichine; streptozotocin; genistein; Streptozotocin; transforming growth factor-x3b2; 1; paramylon; streptozotocin; C-peptide; SKF96365; TRPC6-siRNA; NFAT2-siRNA; ICG-001; short-chain fatty acids; acetate; propionate; butyrate; GPR43 agonist; TRAIL; PF429242; liraglutide; enalapril; canagliflozin; isoprenaline; Liuwei Dihuang pill; streptozotocin; six novel poricoic acids from Poria cocos; poricoic acid ZM; poricoic acid ZP; secolanostane tetracyclic triterpenoids; emodin; HGF; traditional Chinese medicine; Western medicine therapies; Sauchinone; Shenkang VII recipe; rhEPO; MOCK-MPs; hEPO-MPs; Calcium dobesilate; topiroxostat; siXDH; Ginkgo biloba extract; Streptozotocin; recombinant thrombomodulin | Details |
| S03 | anti-inflammatory | Anti-inflammatory; Anti-fibrosis; Anti-oxidative stress; Anti-inflammatory; Immunotherapy; Anti-inflammatory; Anti-apoptosis; Anti-inflammatory; Anti-inflammatory; Anti-oxidative stress; Anti-inflammatory; Anti-fibrosis; Anti-oxidative stress; Anti-inflammatory; Anti-apoptosis; Anti-inflammatory; Anti-oxidative stress; Anti-fibrosis; Enhance lipid metabolism; Anti-inflammatory; Anti-fibrosis; Enhance lipid metabolism; Anti-inflammatory; Anti-inflammatory; Immunosuppressive; Anti-inflammatory; inducing apoptosis in those cells; Anti-inflammatory; Improve insulin resistance; Enhance lipid metabolism; Regulating intestinal flora; Anti-hypertensive; Anti-oxidative stress; Anti-inflammatory; Anti-fibrosis; Improve insulin resistance; Enhance lipid metabolism; Anti-inflammatory; anti-inflammatory; anti-oxidative stress; Anti-fibrosis; Anti-inflammatory; Anti-apoptosis; Anti-hypertensive; Anti-inflammatory; Anti-fibrosis; Anti-inflammatory; Immunotherapy; Anti-hypertensive; Anti-oxidative stress; Anti-inflammatory; Anti-inflammatory; Improve insulin resistance; Anti-inflammatory; Anti-oxidative stress; Anti-apoptosis; Anti-hypertensive; Anti-inflammatory; Anti-inflammatory; Lifestyle measures; non-steroidal anti-inflammatory agents (NSAIDs); Anti-inflammatory; Anti-fibrosis; Enhance lipid metabolism; Regulating intestinal flora; Improve insulin resistance; Enhance lipid metabolism; Anti-inflammatory; Enhance lipid metabolism; Anti-oxidative stress; Anti-inflammatory; anti-inflammatory; Anti-fibrosis; Anti-inflammatory; Cell therapy; Anti-inflammatory; Anti-fibrosis; Anti-inflammatory; Anti-fibrosis; Anti-apoptosis; Immunotherapy; Anti-inflammatory; Improve insulin resistance; Anti-oxidative stress; Anti-inflammatory; Anti-fibrosis; non-steroidal anti-inflammatory drugs (NSAIDs) treatment; Anti-fibrosis; Anti-inflammatory; Anti-hypertensive; Anti-oxidative stress; Anti-inflammatory; Anti-fibrosis; Anti-apoptosis; Anti-fibrosis; Anti-inflammatory; Anti-oxidative stress; Anti-inflammatory renoprotection; anti-inflammatory effect; Enhance lipid metabolism; Anti-inflammatory; Anti-fibrosis; Anti-oxidative stress; Anti-inflammatory; Anti-oxidative stress; Anti-lipogenesis; Anti-fibrosis | NF-κB; TNF-α; NF-κB; FGF23; MAPK; caspase-3; Bcl-2; Nrf2; HO-1; p38 MAPK; JNK; FXR; TNF-α; IL-1β; IL-6; AMPK; PPAR; IL-1β; IL-6; TNF-α; ACE; Smad4; PKD1; p62; mTOR; AMPK; HIF; HIF; Smad2/3; Smad2/3; VEGFA; IL-6; MAPK; IL-1β; EGFR; TLR4; IL-6; Wnt/β-catenin; HO-1; NF-κB; TLR4; NF-κB; NF-κB; STAT3; JAK2; NOX4; NF-κB; Nrf2; SGLT2; HIF; SIRT1; JAK1; JAK2; TLR4; Smad2/3; IL-17; IL-6; PI3K; AKT; IL-6; IL-1β; TNF-α; TGF-β; EGF; IL-17; AMPK; NOX4; caspase-3; NOX4; NLRP3; caspase-1; IL-1β; ERK; JNK; p38 MAPK; NLRP3; NLRP3; NF-κB; HIF; hepcidin | MRI-1867; JD5037; 1400W; prednisolone; methotrexate; eldecalcitol; teriparatide; denosumab; streptozotocin; chloroquine; dexamethasone; 5-aminosalicylates; azathioprine; methotrexate; Glatiramer acetate; Glatiramer; paricalcitol; Oleuropein; methyl corosolate; uvaol; oleanolic acid; phenolic-rich açaí seed extract; BML-111; ML385; Recombinant thrombomodulin; obeticholic acid (OCA; 6-ethyl chenodeoxycholic acid); tropifexor; nidufexor; Tripterygium wilfordii Hook F; C4BP(x3b2; -); cyclophosphamide; methylprednisolone; cyclophosphamide; tripterygium wilfordii multiglycosides; prednisone; Astragalus; Salvia miltrorrhiza; Polygala fallax Hemsl; compound Sanqi granules; metformin; Okadaic acid; berberine; NOX5 siRNA; Tectorigenin; gentamicin; miR-218 inhibitor; methylprednisolone; prednisolone; mycophenolate mofetil; cyclosporine A; cyclophosphamide; rituximab; azathioprine; tacrolimus; propionate; Hirudin; Hsub2/subS; NO; Hsub2/subSxa0; xa0; NO; USC; prednisolone; mizoribine; angiotensin-converting enzyme inhibitors; steroids; cyclophosphamide; Korean red ginseng; Panax ginseng C.A. Mey.; streptozotocin; probiotics; Lactobacillus; Bifidobacterium; Sodium-glucose cotransporter 2 inhibitors; SGLT2 inhibitors; intravenous immunoglobulins; glucocorticoids; cyclophosphamide; azathioprine; Cyanidin-3-glucoside; Curcumin; quercetin; formononetin; calycosin; 7-O-methylisomucronulatol; quercetin; 1,25sub2/subDsub3/sub; parthenolide; insulin; Tocilizumab; Oral prednisolone; Astragaloside IV; Akebia saponin D; dioscin; streptozocin; Baicalin; tegafur/gimeracil/oteracil; furosemide; prednisolone; methylprednisolone; prednisolone; steroid; allopurinol; β-Caryophyllene; Colchicine; systemic/intra-articular corticosteroids; non-steroidal anti-inflammatory agents; IL-1 inhibitors; immunosuppressive therapy; STZ; dapagliflozin; streptozocin; Ergosterol; Streptozotocin; corticosteroids; cyclophosphamide; tofacitinib; inulin; Sodium-glucose cotransporter 2 inhibitors; curcumin; camptothecin; streptomycin; JAK inhibitors; ruxolitinib; Plantamajoside; methylprednisolone; intravenous immunoglobulin; vitamin D receptor agonists; paricalcitol; Am80; all-trans retinoic acid; Capsicum annuum L.; HPMA copolymer-based dexamethasone prodrug; PEG-based dexamethasone prodrug; glucocorticoid; cyclophosphamide; psoralen; Caffeine; glucocorticoids; Streptozotocin; paramylon; Campath; IV steroid; IV antibiotics; clindamycin; cMet agonistic antibody; short-chain fatty acids; acetate; propionate; butyrate; GPR43 agonist; Infliximab; corticosteroids; secukinumab; prednisolone; methylprednisolone; Cyclophosphamide; non-steroidal anti-inflammatory drugs; methotrexate; steroid; Dexamethasone; Tiliacora triandra extract; 5,7-dihydroxy-6-oxoheptadecanoic acid; liraglutide; enalapril; canagliflozin; isoprenaline; Liuwei Dihuang pill; streptozotocin; six novel poricoic acids from Poria cocos; poricoic acid ZM; poricoic acid ZP; secolanostane tetracyclic triterpenoids; Chuanxiong Rhizoma; Myricanone; Wallichilide; Sitosterol; Chloroquine; Amodiaquine; Streptozotocin; statins; atorvastatin; Allopurinol; febuxostat; Terminalia bellerica; saxagliptin; Adriamycin; baru almond oil; mineral oil; Epicatechin; 2,3-dihydroxybenzoic acid; 3,4-dihydroxyphenylacetic acid; 3-hydroxyphenylpropionic acid; Sauchinone; Shenkang VII recipe; porcine collagen hydrolysate; prolyl-hydroxyproline; APX-115; sodium nitrite; isoquercetin; topiroxostat; siXDH; Ginkgo biloba extract; Streptozotocin | Details |
| S04 | anti-lipogenesis | Enhance lipid metabolism; Anti-lipogenesis; Anti-inflammatory; Anti-oxidative stress; Anti-lipogenesis; Anti-fibrosis | AMPK | Liraglutide; Ginkgo biloba extract; Streptozotocin | Details |
| S05 | anti-oxidative stress | Anti-inflammatory; Anti-fibrosis; Anti-oxidative stress; Anti-inflammatory; Anti-oxidative stress; Enhance lipid metabolism; Improve insulin resistance; Anti-oxidative stress; Anti-oxidative stress; Anti-oxidative stress; Anti-inflammatory; Anti-apoptosis; Anti-inflammatory; Anti-oxidative stress; Anti-fibrosis; Anti-apoptosis; Anti-oxidative stress; Anti-oxidative stress; Anti-inflammatory; Anti-fibrosis; anti-inflammatory; anti-oxidative stress; Anti-oxidative stress; Anti-inflammatory; Anti-inflammatory; Anti-oxidative stress; Anti-apoptosis; Anti-oxidative stress; Anti-fibrosis; Enhance lipid metabolism; Anti-oxidative stress; Anti-inflammatory; Anti-oxidative stress; Anti-fibrosis; Anti-apoptosis; Anti-oxidative stress (Epigallocatechin-3-gallate (EGCG) activates Nrf2/ARE signaling pathway by downregulating Keap1 and boosting nuclear Nrf2 level); Anti-hypertensive; Anti-oxidative stress; Improve insulin resistance; Anti-oxidative stress; Anti-inflammatory; Anti-fibrosis; Anti-oxidative stress; Anti-inflammatory; Anti-fibrosis; Anti-apoptosis; Anti-oxidative stress; Anti-apoptosis; Anti-fibrosis; Anti-inflammatory; Anti-oxidative stress; relieving oxidative stress; Enhance lipid metabolism; Anti-inflammatory; Anti-fibrosis; Anti-oxidative stress; Anti-inflammatory; Anti-oxidative stress; Anti-lipogenesis; Anti-fibrosis | TNF-α; NF-κB; MAPK; caspase-3; Bcl-2; DPP4; Nrf2; HO-1; p38 MAPK; JNK; SGLT2; mineralocorticoid receptor; MMP-9; AMPK; HIF; HIF; Smad2/3; Smad2/3; VEGFA; IL-6; MAPK; IL-1β; EGFR; Wnt/β-catenin; HO-1; NF-κB; NOX4; MAPK; NF-κB; STAT3; JAK2; NOX4; NF-κB; Nrf2; NF-κB; NOX4; SIRT1; AMPK; Nrf2; AMPK; NOX4; caspase-3; ERK; JNK; p38 MAPK; NLRP3; NLRP3; NF-κB; AMPK; AMPK; Bcl-2; Nrf2; Smad2/3; NOX4 | MRI-1867; JD5037; 1400W; Glatiramer acetate; Glatiramer; Berberine; GKT137831; febuxostat; topiroxostat; Oleuropein; Resveratrol; Dipeptidyl peptidase-4 inhibitors; alogliptin; saxagliptin; sitagliptin; teneligliptin; phenolic-rich açaí seed extract; BML-111; ML385; empagliflozin; dapagliflozin; ramipril; hydro-chloro-thiazide; iN/i-acetylcysteine; aminoguanidine; metformin; l-cysteine; NOX5 siRNA; gentamicin; syringic acid; streptozotocin; tamarind seed coat ethanol extract; Finerenone; USC; probiotics; Lactobacillus; Bifidobacterium; Sodium-glucose cotransporter 2 inhibitors; SGLT2 inhibitors; Cyanidin-3-glucoside; N-acetylcysteine; quercetin; formononetin; calycosin; 7-O-methylisomucronulatol; quercetin; streptozotocin; Astragaloside IV; Akebia saponin D; Retinoic acid; Folic acid; N-acetyl-cysteine; Baicalin; β-Caryophyllene; Ergosterol; Streptozotocin; GKT137831; GKT13783; Sodium-glucose cotransporter 2 inhibitors; Plantamajoside; Capsicum annuum L.; dencichine; reactive oxygen species scavenger; Ang II receptor blockers; Epigallocatechin-3-gallate; type 1 angiotensin II receptor blockade; olmesartan; short-chain fatty acids; acetate; propionate; butyrate; GPR43 agonist; Tiliacora triandra extract; 5,7-dihydroxy-6-oxoheptadecanoic acid; canagliflozin; isoprenaline; streptozotocin; recombinant human clusterin protein; six novel poricoic acids from Poria cocos; poricoic acid ZM; poricoic acid ZP; secolanostane tetracyclic triterpenoids; Chloroquine; Amodiaquine; Streptozotocin; Allopurinol; febuxostat; Terminalia bellerica; Epicatechin; 2,3-dihydroxybenzoic acid; 3,4-dihydroxyphenylacetic acid; 3-hydroxyphenylpropionic acid; Sauchinone; GLP-1; liraglutide; exendin-4; Cinacalcet; mitoquinone; ML385; sodium nitrite; isoquercetin; vitamin E; selenium; SIS3; Forskolin; topiroxostat; siXDH; Ginkgo biloba extract; Streptozotocin; puromycin aminonucleoside; amiloride | Details |
| S07 | antihypertensive | Anti-fibrosis; Anti-hypertensive; Anti-hypertensive; antihypertensive medications; multidrug combination antihypertensive treatment; empirical addition (or increase in the dose) of an antihypertensive agent of a different class""; Anti-hypertensive; Lifestyle measures; Anti-inflammatory; Improve insulin resistance; Enhance lipid metabolism; Regulating intestinal flora; Anti-hypertensive; Anti-hypertensive; Anti-inflammatory; Anti-fibrosis; Anti-inflammatory; Immunotherapy; Anti-hypertensive; Immunosuppressive treatment; Anti-hypertensive; Anti-hypertensive; Anti-platelet aggregation; other antihypertensive drugs; antihypertensive therapy; Anti-hypertensive; Anti-inflammatory; Anti-hypertensive (standard antihypertensive treatment; intensive antihypertensive treatment); Blood pressure management; Anti-hypertensive; Enhance lipid metabolism; Anti-hypertensive; Enhance lipid metabolism; Anti-platelet aggregation; Improve insulin resistance; Anti-hypertensive; Anti-hypertensive; Anti-oxidative stress; antihypertensives; Lifestyle measures; Anti-hypertensive; Anti-fibrosis; Anti-inflammatory; Anti-hypertensive | ACE; Smad4; PKD1; angiotensin receptor; SGLT2; angiotensin II receptor; mineralocorticoid receptor; ACE | riociguat; sGC stimulators; sGC activators; antihypertensive medications; carvedilol; lercanidipine; enalapril; folic acid; retinoic acid; angiotensin II; antihypertensive drug; Tripterygium Wilfordii Hook F; valsartan; Renin-angiotensin system inhibitors; diuretics; calcium channel blocker; corticosteroid; anti-hypertensive treatment; NSAIDs; naproxen; celecoxib; proton pump inhibitor; non-selective NSAID; selective cyclo-oxygenase-2 inhibitor; renin-angiotensin system blockers; antihypertensive agent; cilnidipine; valsartan; RAAS-is; steroids; immunosuppressors; amiloride; hydrochlorothiazide; berberine; Aliskiren; calcium channel blocker; angiotensin II receptor blocker; ARB; Chlorthalidone; Hydrochlorothiazide; Hsub2/subS; NO; Hsub2/subSxa0; xa0; NO; prednisolone; mizoribine; angiotensin-converting enzyme inhibitors; ACEI; eculizumab; antihypertensive agents; antithrombotics; antianemics; proton pump inhibitors; allopurinol; rilmenidine; long-term benzodiazepines; anticholinergic drugs; hydroxyzine; Qian Yang Yu Yin Granule; RAAS blockers; other antihypertensive drugs; antihypertensives; antihypertensive classes; antihypertensive therapy; melatonin; RAASi; Aliskiren; ARBs; ACEIs; tegafur/gimeracil/oteracil; furosemide; prednisolone; angiotensin receptor blockers; valsartan; antihypertensive drugs; fosinopril; valsartan; Canagliflozin; sodium glucose co-transporter 2 inhibitors; Aspirin; Antihypertensive; Lipid-Lowering Treatment; Sodium-glucose cotransporter 2 inhibitors; angiotensin II receptor blocker; Spironolactone; KBP-5074; captopril; enalaprilate; lisinopril; losartan; valsartan; furosemide; pravastatin; simvastatin; Renin Angiotensin System inhibitors; ACE inhibitors; diuretics; β-blockers; Thiazide diuretics; dihydropyridine calcium-channel blockers; angiotensin-converting enzyme inhibitors; angiotensin receptor blockers; calcium-channel blockers; thiazide-like diuretics; lisinopril; Edarbyclor; azilsartan medoxomil; chlorthalidone; hydrochlorothiazide; aliskiren; ARB; enalapril; non-steroidalanti-inflammatory drugs; antihypertensive treatment; Chlorthalidone; loop diuretics; angiotensin-converting enzyme inhibitor; angiotensin receptor blocker; statin; captopril; tiopronin; active form of dalcetrapib; active metabolite of prasugrel, R-138727; Liuwei Dihuang pills; metformin hydrochloride sustained-release tablets; irbesartan tablets; renin-angiotensin-aldosterone system inhibitor; type 1 angiotensin II receptor blockade; olmesartan; steroid; immunosuppressive agents; enalapril; corticosteroid treatment; Angiotensin-converting-enzyme inhibitors; antihypertensives; GLP-1 receptor analogue; SGLT2-inhibitor; sacubitril/valsartan; valsartan; Sulodexide; liraglutide; enalapril; ACE-I/ARBs; angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers; labetalol; ACEi; ARB; ARBs | Details |
| S09 | cell therapy | high-dose melphalan/autologous peripheral blood stem cell transplantation; Cell therapy; Cell therapy; Anti-inflammatory; Anti-fibrosis; Cell therapy; Anti-fibrosis | B cells; IL-6; IL-1β; TNF-α; TGF-β; EGF; SIRT1 | chemotherapy; high-dose melphalan; melatonin; granulocyte-colony stimulating factor; metformin; Mesenchymal stem cells; Human gingiva derived MSCs; Streptozotocin; streptozotocin; C-peptide; SIRT1 activators | Details |
| S12 | enhance lipid metabolism | Enhance lipid metabolism; Improve insulin resistance; Anti-oxidative stress; Anti-fibrosis; Enhance lipid metabolism; Enhance lipid metabolism; Anti-inflammatory; Anti-fibrosis; Enhance lipid metabolism; Enhance lipid metabolism; Anti-inflammatory; Anti-inflammatory; Improve insulin resistance; Enhance lipid metabolism; Regulating intestinal flora; Anti-hypertensive; Improve insulin resistance; Enhance lipid metabolism; Anti-inflammatory; Improve insulin resistance; Enhance lipid metabolism; Regulating intestinal flora; Anti-fibrosis; Anti-platelet aggregation; Enhance lipid metabolism; Enhance lipid metabolism; Anti-lipogenesis; Anti-fibrosis; Enhance lipid metabolism; Improve insulin resistance; Anti-inflammatory; Anti-fibrosis; Enhance lipid metabolism; Regulating intestinal flora; Improve insulin resistance; Enhance lipid metabolism; Anti-inflammatory; Enhance lipid metabolism; Anti-oxidative stress; Anti-inflammatory; Anti-hypertensive; Enhance lipid metabolism; Anti-apoptosis; Enhance lipid metabolism; Anti-hypertensive; Enhance lipid metabolism; Anti-platelet aggregation; Enhance lipid metabolism; Anti-platelet aggregation; Enhance lipid metabolism; Anti-inflammatory; Anti-fibrosis; Anti-oxidative stress | PPAR; FXR; AMPK; PPAR; Smad2/3; Smad4; PCSK9; AMPK; ACE; SGLT2; HIF; SIRT1 | Berberine; miR-9-5p; obeticholic acid (OCA; 6-ethyl chenodeoxycholic acid); tropifexor; nidufexor; Pemafibrate; conventional fibrates; Tripterygium wilfordii Hook F; berberine; Tectorigenin; Rehmannia glutinosa leaves total glycoside; evolocumab; statin products; icodextrin dialysate; insulin; dual antiplatelet therapy; statins; beta-blockers; Liraglutide; ACE inhibitors; ATsub1/sub receptor antagonists; N-acetyl-seryl-aspartyl-lysyl-proline; glycolysis inhibitors; prolyl oligopeptidase inhibitor S17092; imidapril; TA-606; dapagliflozin; streptozocin; fenofibrate; inulin; Sodium-glucose cotransporter 2 inhibitors; captopril; enalaprilate; lisinopril; losartan; valsartan; furosemide; pravastatin; simvastatin; fenofibrate; miRNA antagomiR; captopril; tiopronin; active form of dalcetrapib; active metabolite of prasugrel, R-138727; statins; topiroxostat; siXDH | Details |
| S14 | immunotherapy | immunosuppressants; immunosuppressive medications; immunosuppression; Immunotherapy; immunosuppressive treatments; Immunosuppressive therapy; immune-suppressive medications; Anti-inflammatory; Immunotherapy; Standard CNI-based mammalian target of rapamycin-free immunosuppression; Immunosuppression; steroid-sparing immunosuppressive protocols; Immunoadsorption; immunosuppressive therapy; Anti-inflammatory; Immunosuppressive; Immunosuppressive treatment; Immunoregulation; Immunosuppressive therapy with cyclophosphamide (CTX); Anti-inflammatory; Immunotherapy; Anti-hypertensive; Immunosuppressive treatment; Anti-hypertensive; Immunization with PTX3 to incite anti-PTX3 antibodies; immunosuppressive drugs; Immunotherapy (predizone; immunosuppressive therapies; Enhanced immunosuppressive treatment; Immunosuppressant therapy; checkpoint inhibitor (CPI) immunotherapy plus conventional chemotherapy; [Immunotherapy; targeting the mucosal immune system dysregulation underlying IgAN pathogenesis with a pH-modified formulation of budesonide; immunosuppression (primarily glucocorticoids); immunosuppressors; systemic immunosuppressant; Immunotherapy (rituximab); Intravenous immunoglobulins; Immunotherapy; Anti-inflammatory; other immunosuppressives; Immunotherapy; Genetic therapy; 'classical' immunosuppressive drugs; Immunotherapy (anti-PD1 antibodies: nivolumab or pembrolizumab); corticosteroids plus immunosuppressant; immunosuppressive agents; immunosuppressive regimen; immunosuppressive drugs; immunosuppressive therapy; Immunosuppressive intervention | angiotensin receptor; IL-2; calcineurin; CD20; FGF23; C5; PLA2R; CD20; JNK; ERK; MAPK; NLRP3; PLA2R; IL-6; B cells; IL-17; PD-1; Smad2/3; p38 MAPK; C3 | ACE-Is; ARBs; steroids; immunosuppressants; immunosuppressive medications; steroids; immunosuppression; ustekinumab; immunosuppressant; immunosuppressive treatments; corticosteroids; immune-suppressive medications; immunosuppressive medications; rituximab; RTX; IL-2; prednisolone; methotrexate; eldecalcitol; teriparatide; denosumab; calcineurin inhibitors; Sirolimus; ofatumumab; rituximab; calcineurin inhibitors; antiproliferative agents; prednisone; IVIg; SCIg; 5-aminosalicylates; azathioprine; methotrexate; Triptolide; immunosuppressants; corticosteroids; glucocorticoid; vitamin D supplementation; active vitamin D; oral phosphate; magnesium supplementation; recombinant human growth hormone; alemtuzumab; Recombinant thrombomodulin; Yi-Qi-Qing-Jie formula; prednisolone; cyclophosphamide; rituximab; steroids; mycophenolate mofetil; tacrolimus; basiliximab; antithymocyte globulins; valganciclovir; renin-angiotensin-aldosterone system blockers; Eculizumab; immunosuppressive therapy; Rituximab; steroids; cyclosporine; ofatumumab; rituximab; monoclonal antibodies; humanized anti-CD20 therapies; ofatumumab; methylprednisolone; cyclophosphamide; tripterygium wilfordii multiglycosides; prednisone; Belimumab; Benlysta; steroids; corticosteroids; immunosuppressive medication; methylprednisolone; prednisolone; mycophenolate mofetil; cyclosporine A; cyclophosphamide; rituximab; azathioprine; tacrolimus; Tris dipalladium; Tris DBA; Denosumab; cyclophosphamide; Tacrolimus; glucocorticoid; Ustekinumab; infliximab; steroid; prednisolone; mizoribine; angiotensin-converting enzyme inhibitors; steroids; cyclophosphamide; ACEI; eculizumab; steroid; steroids; immunosuppressants; PF-06730512; intravenous immunoglobulins; glucocorticoids; cyclophosphamide; azathioprine; Iguratimod; prednisone; denosumab; human recombinant PTX3; Rituximab; steroids; calcineurin inhibitors; ofatumumab; immunosuppressive drugs; prednizone; cyclosporine A; enoxaparine; Tocilizumab; Lenalidomide; anthracycline; prednisolone; prednisolone; mycophenolate mofetil; cyclophosphamide; Mycophenolic acid; MPA; enhanced immunosuppressive treatment; corticosteroids; cyclophosphamide; RAAS blockers; immunosuppression; herbal medication; herbal supplement; IV cyclophosphamide; steroids; cyclosporine; sirolimus; steroid; immunosuppressants; corticosteroids; cyclophosphamide; tofacitinib; FTY720; SEW2871; TY52156; renin angiotensin system inhibitors; corticosteroids; immunosuppressant; Checkpoint inhibitor; conventional chemotherapy; corticosteroids; anti-IL-12/23 p40 antibody; abatacept; budesonide; corticosteroid; rituximab (RTX; anti-CD20); belimumab (BLM; anti-BAFF); prednisolone; rituximab; cyclophosphamide; mycophenolate mofetil; glucocorticoids; immune checkpoint inhibitors; angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers; diuretics; corticosteroids; rituximab; immunosuppressive treatment; methylprednisolone; intravenous immunoglobulin; corticosteroids; immunosuppressors; systemic immunosuppressant; rituximab; steroids; tacrolimus; cyclosporine; cyclophosphamide; mycophenolate mofetil; Intravenous immunoglobulins; Rituximab; glucocorticoid; cyclophosphamide; immunosuppressants; certolizumab pegol; methotrexate; infliximab; rituximab; corticosteroids; cyclophosphamide; cyclophosphamide; cyclo; rituximab; belimumab; cyclophosphamide; glucocorticoids; steroid; pulse methylprednisolone; cyclophosphamide; cyclosporine; mycophenolate mofetil; rituximab; abatacept; Campath; IV steroid; IV antibiotics; clindamycin; corticosteroids; mycophenolate mofetil; other immunosuppressives; ecluzimab; Infliximab; corticosteroids; secukinumab; prednisolone; methylprednisolone; Cyclophosphamide; miR-10a-3p agomir; miR-10a-3p antagomir; REG3A low expression vector; rituximab; corticosteroids; ""'classical' immunosuppressive drugs; Janus kinase inhibitors""; antiviral medications; corticosteroid; cyclophosphamide; mycophenolate mofetil; nivolumab; pembrolizumab; renin-angiotensin-aldosterone system inhibitors; proton-pump inhibitors; corticosteroids; corticosteroids; immunosuppressant; tacrolimus; mycophenolate mofetil; tocilizumab; high dose corticosteroids; glucocorticoids; immunosuppressants; cyclosporine; rituximab; intravenous immunoglobulins; IVIg; methylprednisolone; cyclophosphamide; glucocorticoids; cyclophosphamides; steroids; immunosuppressive drugs; immunosuppressive; rituximab; nivolumab; daratumumab; bortezomib; melphalan; prednisone; thalidomide | Details |
| S15 | improve insulin resistance | Enhance lipid metabolism; Improve insulin resistance; Anti-oxidative stress; Anti-inflammatory; Improve insulin resistance; Enhance lipid metabolism; Regulating intestinal flora; Anti-hypertensive; Improve insulin resistance; Enhance lipid metabolism; Anti-inflammatory; Improve insulin resistance; Enhance lipid metabolism; Regulating intestinal flora; Anti-fibrosis; Anti-inflammatory; Improve insulin resistance; Anti-fibrosis; Enhance lipid metabolism; Improve insulin resistance; Regulating intestinal flora; Improve insulin resistance; Enhance lipid metabolism; Anti-inflammatory; Improve insulin resistance; Anti-hypertensive; Improve insulin resistance; Anti-oxidative stress; Anti-inflammatory; Anti-fibrosis | AMPK; PPAR; Smad2/3; Smad4; ACE | Berberine; berberine; Tectorigenin; Rehmannia glutinosa leaves total glycoside; parthenolide; insulin; ACE inhibitors; ATsub1/sub receptor antagonists; N-acetyl-seryl-aspartyl-lysyl-proline; glycolysis inhibitors; prolyl oligopeptidase inhibitor S17092; imidapril; TA-606; inulin; Liuwei Dihuang pills; metformin hydrochloride sustained-release tablets; irbesartan tablets; short-chain fatty acids; acetate; propionate; butyrate; GPR43 agonist | Details |
| S16 | lifestyle measures | Lifestyle measures; adequate dietary or supplemental vitamin D and calcium intake; avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies; Dietary supplementation with grains containing high β-glucan fiber; metabolic bariatric surgery; intensive lifestyle intervention; A low-glycemic, low-phosphate dietary intervention; Anti-hypertensive; Lifestyle measures; Dietary counseling; Adequate dietary or supplemental vitamin D and calcium intake; Avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies; dietary flavonoid supplementation; lifestyle modifications including exercise and an energy-restricted diet; Anti-inflammatory; Lifestyle measures; lifestyle interventions; Lifestyle measures; Anti-hypertensive; Hemodialysis; diet modifications; intensive dietary modifications | Klotho; SGLT2 | trelagliptin; trelagliptin; bisphosphonates; alendronate; risedronate; zoledronic acid; denosumab; anabolic agents; vitamin D; calcium; oat β-glucan; metformin; rosiglitazone; insulin; insulin therapy; amiloride; hydrochlorothiazide; Tolvaptan; agrochemicals; alendronate; risedronate; zoledronic acid; denosumab; anabolic agents; vitamin D; dietary flavonoid supplementation; metformin; linagliptin; fixed-dose combination of linagliptin/metformin; Kangen-karyu extract; phosphate binders; vitamin D; calcimimetics; allopurinol; testosterone gel; sodium-glucose cotransporter-2 inhibitors; glucagon-like peptide-1 receptor agonists; Sulodexide; uric acid lowering drugs; calcium salts; calcium; vitamin D; antiresorptive; anabolic agent | Details |
| S18 | regulating intestinal flora | Anti-inflammatory; Improve insulin resistance; Enhance lipid metabolism; Regulating intestinal flora; Anti-hypertensive; Improve insulin resistance; Enhance lipid metabolism; Regulating intestinal flora; Anti-fibrosis; gut microbiota modulation; innovative absorption-based approach; gut microbiota reprogramming; Regulating intestinal flora; Improve insulin resistance; Enhance lipid metabolism; Anti-inflammatory; Regulating intestinal flora; Modulation of IS production in the gut microbiota | Smad2/3; Smad4 | berberine; Rehmannia glutinosa leaves total glycoside; synbiotic; broad-spectrum oral antibiotics; sodium acetate; GPR43 siRNA; inulin; choline analogues; histidine-based scaffold; isoquercitrin | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I02 | 1184 | nephrotic syndrome | "A nephrosis characterized by marked increase in glomerular protein permeability resulting in marked elevation of urine protein levels, hypoalbuminemia, hyperlipidemia, and hypercoagulability." [url:https\://en.wikipedia.org/wiki/Nephrotic_syndrome, url:https\://www.niddk.nih.gov/health-information/kidney-disease/nephrotic-syndrome-adults] | Details |