As the basic substance of life, carbohydrate molecules participate in almost all aspects of life activities and play various important biological functions. Based on the extensive biological functions of carbohydrate, the development of carbohydrate-based drugs has been an important field of drug research for a long time. Since 2000, the field of glycochemistry, glycobiology and glycochemical biology has developed rapidly, which has brought many opportunities for the research and development of carbohydrate-based drugs.
According to statistics, from 2000 to 2021, a total of 54 carbohydrate-based drugs were launched in the market. Drugs are classified by indication, including antiviral, antibacterial/antiparasitic, antineoplastic, antidiabetic, cardiovascular drugs and nervous system drugs.
| No. | Generic name | Indications | Year | Country | Chemical category |
| 1 | Remdesivir | Antiviral | 2020 | USA | Nucleoside |
| 2 | Molnupiravir | Antiviral | 2021 | UK | Nucleoside |
| 3 | Azvudine | Antiviral | 2021 | China | Nucleoside |
| 4 | Entecavir | Antiviral | 2005 | USA | Nucleoside |
| 5 | Telbivudine | Antiviral | 2006 | USA | Nucleoside |
| 6 | Clevudine | Antiviral | 2006 | South Korea | Nucleoside |
| 7 | Sofosbuvir | Antiviral | 2013 | USA | Nucleoside |
| 8 | Maribavir | Antiviral | 2021 | USA | Nucleoside |
| 9 | Peramivir | Antiviral | 2010 | Japan | Nucleoside |
| 10 | Laninamivir Octanoate | Antiviral | 2010 | Japan | Nucleoside |
| 11 | Carragelose | Antiviral | 2013 | Europe | NP-deriveda |
| 12 | Telithromycin | Antibacterial | 2001 | USA | NP-derived |
| 13 | Cethromycin | Antibacterial | 2009 | USA | NP-derived |
| 14 | Carrimycin | Antibacterial | 2019 | China | NP-derived |
| 15 | Fidaxomicin | Antibacterial | 2011 | USA | NP-derived |
| 16 | Telavancin | Antibacterial | 2009 | USA | NP-derived |
| 17 | Oritavancin | Antibacterial | 2014 | USA | NP-derived |
| 18 | Dalbavancin | Antibacterial | 2014 | USA | NP-derived |
| 19 | Plazomicin | Antibacterial | 2018 | USA | NP-derived |
| 20 | Paromomycin | Antiparasitic | 2006 | India | NP-derived |
| 21 | Azacitidine | Anticancer | 2004 | USA | Nucleoside |
| 22 | Decitabine | Anticancer | 2006 | USA | Nucleoside |
| 23 | Clofarabine | Anticancer | 2004 | USA | Nucleoside |
| 24 | Nelarabine | Anticancer | 2005 | USA | Nucleoside |
| 25 | Forodesine | Anticancer | 2017 | Japan | Nucleoside |
| 26 | Amrubicin | Anticancer | 2002 | Japan | NP-derived |
| 27 | Midostaurin | Anticancer | 2017 | USA | NP-derived |
| 28 | Mifamurtide | Anticancer | 2009 | Europe | NP-derived |
| 29 | Dapagliflozin | Antidiabetic | 2012 | Europe | NP-derived |
| 30 | Canagliflozin | Antidiabetic | 2013 | USA | NP-derived |
| 31 | Empagliflozin | Antidiabetic | 2014 | Europe | NP-derived |
| 32 | Ipragliflozin | Antidiabetic | 2014 | Japan | NP-derived |
| 33 | Luseogliflozin | Antidiabetic | 2014 | Japan | NP-derived |
| 34 | Tofogliflozin | Antidiabetic | 2014 | Japan | NP-derived |
| 35 | Ertugliflozin | Antidiabetic | 2017 | USA | NP-derived |
| 36 | Sotagliflozin | Antidiabetic | 2019 | Europe | NP-derived |
| 37 | Remogliflozin Etabonate | Antidiabetic | 2019 | India | NP-derived |
| 38 | Tinzaparin sodium | Cardiovascular/anticoagulant | 2000 | USA | NP-derived |
| 39 | Fondaparinux Sodium | Cardiovascular/anticoagulant | 2001 | USA | NP-derived |
| 40 | Ticagrelor | Cardiovascular | 2010 | Europe | Nucleoside |
| 41 | Cangrelor | Cardiovascular | 2015 | USA | Nucleoside |
| 42 | Sodium oligomannate | Alzheimer Disease | 2019 | China | NP-derived |
| 43 | Sugammadex | Anesthesia | 2008 | Europe | NP-derived |
| 44 | Diquafosol tetrasodium | Dry eye disease | 2010 | Japan | Nucleoside |
| 45 | Lactitol | Chronic idiopathic constipation | 2020 | USA | NP-derived |
| 46 | Magnesium isoglycyrrhizinate | Anti-inflammatory | 2005 | China | NP-derived |
| 47 | Miglustat | Gaucher disease | 2002 | Europe | NP-derived |
| 48 | Migalastat | Fabry disease | 2016 | Europe | NP-derived |
| 49 | Uridine Triacetate | Hereditary orotic aciduria | 2015 | USA | Nucleoside |
| 50 | Regadenoson | Myocardial perfusion imaging | 2008 | USA | Nucleoside |
| 51 | [99mTc]Tilmanocept | Contrast media | 2013 | USA | NP-derived |
| 52 | Givosiran | siRNA for AHP | 2019 | USA | Glycoconjugate |
| 53 | S. Pneumoniae vaccines | S. Pneumoniae prevention | 2000-2021 | USA, Europe, etc. | Glycoconjugate |
| 54 | Typhim Vi vaccine | Typhim prevention | 2014 | USA | Glycoconjugate |
Carbohydrate-based Antiviral Drugs
1. Remdesivir, sold under the brand name Veklury, is a broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences. It is a nucleotide prodrug of an adenosine analog. It binds to the viral RNA-dependent RNA polymerase and inhibits viral replication by terminating RNA transcription prematurely.
2. Molnupiravir is a small-molecule ribonucleoside prodrug of N-hydroxycytidine (NHC), which has activity against SARS-CoV-2 and other RNA viruses and a high barrier to development of resistance.
3. Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). It has a therapeutic potential and safety profile for the treatment of patients infected with SARS-CoV-2.
4. Entecavir is an antiviral that belongs to a class of drugs known as hepatitis B virus nucleoside reverse transcriptase inhibitors. It is a nucleoside analogue used in the treatment of chronic hepatitis B for patients with active viral replication, histological evidence of active disease, or persistent elevations in liver transaminases.
5. Telbivudine is a thymidine nucleoside analog used for the treatment of chronic hepatitis B with clinical evidence of viral replication or persistent elevations in serum aminotransferases (ALT or AST).
6. Clevudine, a pyrimidine analog, is a potent inhibitor of HBV replication both in vitro and in vivo.
7. Sofosbuvir is a nucleotide analog inhibitor of hepatitis C virus NS5B polymerase, which is the key enzyme mediating HCV RNA replication.
8. Maribavir (previously known as 1263W94) is a novel benzimidazole riboside compound. It is an orally bioavailable anti-CMV compound that targets and inhibits the UL97 protein kinase and its natural substrates.
9. Peramivir is a neuraminidase inhibitor, acting as a transition-state analogue inhibitor of influenza neuraminidase and thereby preventing new viruses from emerging from infected cells.
10. Laninamivir octanoate (CS-8958), a prodrug of Laninamivir, is a long-acting neuraminidase (NA) inhibitor with anti-influenza virus activity.
11. Carragelose is a sulfated polymer from red seaweed and is a unique, broadly active anti-viral compound.
Carbohydrate-based Antibacterial and Antiparasitic Drugs
1. Telithromycin is a semi-synthetic erythromycin derivative. It is a ketolide antibiotic which has an antimicrobial spectrum similar or slightly broader than that of penicillin.
2. Cethromycin is a new ketolide, a semisynthetic derivative of macrolide erythromycin A. It has broad-spectrum activity against Gram-positive, Gram-negative, and atypical bacteria that may be useful for treating several conditions including community-acquired pneumonia, inhalation anthrax, plague, and tularemia.
3. Carrimycin is a 16-member macrolide antibiotic with anticancer activity, and monomeric isovalerylspiramycin I is a main component.
4. Fidaxomicin belongs to the class of medicines known as macrolide antibiotics. It works by killing bacteria or preventing their growth. However, this medicine will not work for colds, flu, or other virus infections. It is used to treat Clostridium difficile-associated diarrhea (CDAD).
5. Telavancin is a lipoglycopeptide antibiotic exerting a concentration-dependent bactericidal activity. It is a semisynthetic derivative of vancomycin with a hydrophobic side chain attached to the vancosamine sugar.
6. Oritavancin is a semisynthetic glycopeptide antibiotic medication for the treatment of serious Gram-positive bacterial infections. Its chemical structure as a lipoglycopeptide is similar to vancomycin.
7. Dalbavancin is a lipoglycopeptide antibiotic derived from teicoplanin, an analog of vancomycin. It possesses a similar spectrum of activity to vancomycin with potent activity against Gram-positive microorganisms, including Streptococcus spp., Enterococcus spp., and both methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA).
8. Plazomicin is a novel semisynthetic parenteral aminoglycoside that inhibits bacterial protein synthesis.
9. Paromomycin is an aminoglycoside antibiotic used in the treatment of acute and chronic intestinal amebiasis, and as an adjunct for the management of hepatic coma.
Carbohydrate-based Anticancer Drugs
1. Azacitidine is a pyrimidine nucleoside analogue used to treat certain subtypes of myelodysplastic syndrome.
2. Decitabine is a chemotherapeutic pyrimidine nucleoside analogue used for the treatment of myelodysplastic syndromes (MDS) by inducing DNA hypomethylation and corresponding alterations in gene expression.
3. Clofarabine is a purine nucleoside antimetabolite. It is used as an antineoplastic agent in the treatment of relapsed or refractory acute lymphoblastic leukaemia.
4. Nelarabine is a prodrug of arabinosylguanine nucleotide triphosphate (araGTP), a type of purine nucleoside analog, which causes inhibition of DNA synthesis and cytotoxicity.
5. Forodesine is a purine nucleoside analog and purine nucleoside phosphorylase (PNP) inhibitor for the treatment of patients with T-cell acute lymphoblastic leukemia and for treatment of B-cell acute lymphocytic leukemia.
6. Amrubicin is a third-generation synthetic anthracycline currently in development for the treatment of small cell lung cancer.
7. Midostaurin is a multi-targeted protein kinase inhibitor that has been investigated for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and advanced systemic mastocytosis. It is a semi-synthetic derivative of staurosporine, an alkaloid from the bacterium Streptomyces staurosporeus.
8. Mifamurtide is a muramyl dipeptide derivative used to treat high grade, resectable, non-metastatic osteosarcoma after surgical resection.
Carbohydrate-based Antidiabetic Drugs
1. Dapagliflozin is a sodium-glucose cotransporter 2 inhibitor used in the management of type 2 diabetes mellitus.
2. Canagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor used to manage hyperglycemia in type 2 diabetes mellitus (DM).
3. Empagliflozin is an inhibitor of sodium-glucose co-transporter-2 (SGLT2), the transporters primarily responsible for the reabsorption of glucose in the kidney.
4. Ipragliflozin is a novel anti-hyperglycemic agent that lowers plasma glucose through reabsorption which is mediated through SGLT-2 blockade.
5. Luseogliflozin is sodium-glucose cotransporter 2 (SGLT2) inhibitor used in the treatment of type 2 diabetes mellitus.
6. Tofogliflozin is an inhibitor of subtype 2 sodium-glucose transport protein, which is responsible for at least 90% of the glucose reabsorption in the kidney.
7. Ertugliflozin is a SGLT2 inhibitor used to treat type 2 diabetes mellitus.
8. Sotagliflozin is an orally bioavailable inhibitor of the sodium-glucose co-transporter subtype 1 (SGLT1) and 2 (SGLT2), with potential antihyperglycemic activity.
9. Remogliflozin etabonate (RE), an inhibitor of the sodium-glucose transporter 2, improves glucose profiles in type 2 diabetes.
Carbohydrate-based Other Drugs
1. Tinzaparin sodium is a low molecular weight heparin with antithrombotic properties.
2. Fondaparinux sodium is a synthetic, sulfated pentasaccharide, selective factor Xa inhibitor that is indicated in Europe for preventing thrombus formation in patients with acute coronary syndromes (ACS; the focus of this review), including those with ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), or unstable angina.
3. Ticagrelor is a P2Y12 platelet inhibitor used in patients with a history of myocardial infarction or with acute coronary syndrome (ACS) to prevent future myocardial infarction, stroke and cardiovascular death.
4. Cangrelor is an intravenous platelet P2Y12 antagonist characterized by a rapid onset of action and achieving potent P2Y12 inhibitory effects.
5. Sodium oligomannate (GV-971) is an oligosaccharide mixture that is proposed to affect the gut microbiota and reduce immune cell infiltration and inflammation in the brain, and it has shown an ability to inhibit amyloid-β fibril formation.
6. Diquafosol tetrasodium (DQS), a purinergic P2Y2 receptor agonist, stimulates secretion of both water and mucins from the conjunctiva into tears.
7. Lactitol is a sugar alcohol used as a replacement bulk sweetener for low calorie foods with 30%-40% of the sweetness of sucrose.
8. Magnesium isoglycyrrhizinate (MgIG) is a magnesium salt mainly composed of 18α-glycyrrhizic acid stereoisomers and belongs to the fourth generation of glycyrrhizic acid preparations.
9. Miglustat is an oral inhibitor of glucosylceramide synthase which is used in the therapy of type 1 Gaucher disease.
10. Migalastat is a pharmacological chaperone that reversibly binds to the active site of the alpha-galactosidase A (alpha-Gal A) protein (encoded by the galactosidase alpha gene, GLA), which is deficient in Fabry disease.
11. Uridine triacetate, formerly known as vistonuridine, is an orally active prodrug of the naturally occurring nucleoside uridine. It is used for the treatment of hereditary orotic aciduria (Xuriden), or for the emergency treatment of fluorouracil or capecitabine overdose or toxicity (Vistogard).
12. Regadenoson is an A2A adenosine receptor agonist that causes coronary vasodilation and used for myocardial perfusion imagining.
13. (99m)Tc-tilmanocept is a receptor-binding molecular imaging agent approved by the U.S. Food and Drug Administration for lymphatic mapping and lymph node localization in breast cancer, melanoma, clinically node-negative squamous cell carcinoma of the oral cavity, and other solid tumors.
14. Givosiran is a 5-aminolevulinic acid synthase-directed small interfering RNA (siRNA) used in the prophylaxis of acute hepatic porphyria.
Reference:
Carbohydrate-based drugs launched during 2000-2021, Acta Pharmaceutica Sinica B, 2022, ISSN 2211-3835