# Synthetic strategies and therapeutic insights into FDA-approved indole-containing drugs

**Authors:** Tengjiao Yang, Yanfeng Zhang, Peng Liu, Peng Qi, Xiankai Li, Wubin Zhi, Lijie Zhao

PMC · DOI: 10.1080/14756366.2026.2616556 · 2026-01-27

## TL;DR

This review explores FDA-approved drugs containing indole, highlighting their synthetic methods and therapeutic uses to guide future drug development.

## Contribution

The paper offers a comprehensive survey of recent FDA-approved indole-based drugs and their synthetic strategies.

## Key findings

- Indole-based drugs are used in oncology, infectious diseases, and other therapeutic areas.
- Synthetic strategies highlight the versatility of the indole scaffold in drug design.
- The review integrates chemistry and clinical data to guide future drug development.

## Abstract

Indole is a privileged heteroaromatic scaffold in medicinal chemistry, characterised by its unique physicochemical properties, hydrogen-bonding potential, and bioisosteric versatility. Over the past decades, numerous indole-containing drugs have been approved by the Food and Drug Administration (FDA), spanning diverse therapeutic areas including oncology, infectious diseases, gastrointestinal disorders, neurological conditions, and cardiovascular diseases. This review provides a comprehensive survey of FDA-approved indole-based drugs, with particular emphasis on those approved from 2013 to the present. Representative synthetic strategies are highlighted to illustrate the versatility of the indole framework in drug design. Furthermore, we systematically discuss each drug’s pharmacology, mechanisms of action, and clinical applications. By integrating synthetic chemistry with clinical applications, this review aims to provide medicinal chemists and drug developers with guidance for leveraging indole scaffolds in next-generation therapeutic discovery and development.

## Linked entities

- **Chemicals:** indole (PubChem CID 798)

## Full-text entities

- **Genes:** GH1 (growth hormone 1) [NCBI Gene 2688] {aka GH, GH-N, GHB5, GHN, IGHD1A, IGHD1B}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, S1PR3 (sphingosine-1-phosphate receptor 3) [NCBI Gene 1903] {aka C9orf108, C9orf47, EDG-3, EDG3, LPB3, S1P3}, C3 (complement C3) [NCBI Gene 718] {aka AHUS5, ARMD9, ASP, C3a, C3b, CPAMD1}, GHSR (growth hormone secretagogue receptor) [NCBI Gene 2693] {aka GHDP, GHS-R1a, GHSR-1a}, POMC (proopiomelanocortin) [NCBI Gene 5443] {aka ACTH, CLIP, LPH, MSH, NPP, OBAIRH}, PCSK1 (proprotein convertase subtilisin/kexin type 1) [NCBI Gene 5122] {aka BMIQ12, NEC1, PC1, PC1/3, PC3, SPC3}, CFB (complement factor B) [NCBI Gene 629] {aka AHUS4, ARMD14, BF, BFD, CFAB, CFBD}, EPHB2 (EPH receptor B2) [NCBI Gene 2048] {aka BDPLT22, CAPB, DRT, EK5, EPHT3, ERK}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, LEPR (leptin receptor) [NCBI Gene 3953] {aka CD295, LEP-R, LEPRD, OB-R, OBR, huB219}, S1PR1 (sphingosine-1-phosphate receptor 1) [NCBI Gene 1901] {aka CD363, CHEDG1, D1S3362, ECGF1, EDG-1, EDG1}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, ALK (ALK receptor tyrosine kinase) [NCBI Gene 238] {aka ALK1, CD246, NBLST3}, CFTR (CF transmembrane conductance regulator) [NCBI Gene 1080] {aka ABC35, ABCC7, CF, CFTR/MRP, MRP7, TNR-CFTR}, S1PR4 (sphingosine-1-phosphate receptor 4) [NCBI Gene 8698] {aka EDG6, LPC1, S1P4, SLP4}, MC3R (melanocortin 3 receptor) [NCBI Gene 4159] {aka BMIQ9, MC3, MC3-R, OB20, OQTL}, MC4R (melanocortin 4 receptor) [NCBI Gene 4160] {aka BMIQ20}, AR (androgen receptor) [NCBI Gene 367] {aka AIS, AR8, DHTR, HPCX3, HUMARA, HYSP1}, FLT3 (fms related receptor tyrosine kinase 3) [NCBI Gene 2322] {aka CD135, FLK-2, FLK2, STK1}, PARP2 (poly(ADP-ribose) polymerase 2) [NCBI Gene 10038] {aka ADPRT2, ADPRTL2, ADPRTL3, ARTD2, PARP-2, pADPRT-2}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, S1PR2 (sphingosine-1-phosphate receptor 2) [NCBI Gene 9294] {aka AGR16, DFNB68, EDG-5, EDG5, Gpcr13, H218}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, GGH (gamma-glutamyl hydrolase) [NCBI Gene 8836] {aka GATD10, GH}, S1PR5 (sphingosine-1-phosphate receptor 5) [NCBI Gene 53637] {aka EDG8, Edg-8, S1P5, SPPR-1, SPPR-2}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, PARP1 (poly(ADP-ribose) polymerase 1) [NCBI Gene 142] {aka ADPRT, ADPRT 1, ADPRT1, ARTD1, PARP, PARP-1}, PARP3 (poly(ADP-ribose) polymerase family member 3) [NCBI Gene 10039] {aka ADPRT3, ADPRTL2, ADPRTL3, ARTD3, IRT1, PADPRT-3}, HDAC9 (histone deacetylase 9) [NCBI Gene 9734] {aka HD7, HD7b, HD9, HDAC, HDAC7B, HDAC9B}
- **Diseases:** skin hyperpigmentation (MESH:D017495), nausea (MESH:D009325), hemangioma (MESH:D006391), sinus bradycardia (MESH:D012804), viral infections (MESH:D014777), gastrointestinal disorders (MESH:D005767), upper respiratory tract infections (MESH:D012141), brain metastasis (MESH:D009362), COVID-19 infection (MESH:D000086382), CF (MESH:D003550), HSDD (MESH:D020018), dizziness (MESH:D004244), AD (MESH:D000544), headache (MESH:D006261), cardiovascular diseases (MESH:D002318), cognitive impairment (MESH:D003072), deaths (MESH:D003643), dysgeusia (MESH:D004408), GHD (MESH:D004393), hepatic injury (MESH:D056486), constipation (MESH:D003248), weight loss (MESH:D015431), abdominal pain (MESH:D015746), heart rate abnormalities (MESH:D006330), AGHD (MESH:C537404), QT prolongation (MESH:D008133), cardiac toxicity (MESH:D066126), NFTs (MESH:D055956), bradycardia (MESH:D001919), allergic reactions (MESH:D004342), adiposity (MESH:D018205), castration-resistant prostate cancer (MESH:D064129), epithelial ovarian, fallopian tube, or primary peritoneal cancer (MESH:D000077216), endometrial cancer (MESH:D016889), BRCA (MESH:D001943), cardiac dysfunction (MESH:D006331), pulmonary (MESH:D008171), cardiomyopathy (MESH:D009202), pneumonitis (MESH:D011014), arrhythmias (MESH:D001145), diarrhoea (MESH:D003967), paronychia (MESH:D010304), inflammatory (MESH:D007249), obese (MESH:D009765), SCLC (MESH:D055752), rash (MESH:D005076), vasomotor symptoms (MESH:D012223), complement-mediated diseases (MESH:D020274), carcinogenicity (MESH:D011230), IPF (MESH:D054990), ILDs (MESH:D017563), hepatitis C virus infection (MESH:D006526), colitis (MESH:D003092), oncology (MESH:D000072716), myalgia (MESH:D063806), vomiting (MESH:D014839), anaemia (MESH:D000743), multiple myeloma (MESH:D009101), dry skin (MESH:D015352), decreased appetite (MESH:D001068)
- **Chemicals:** methylamine (MESH:C027451), sodium hydride (MESH:C524957), Palladium (MESH:D010165), C (MESH:D002244), ribavirin (MESH:D012254), sulphonamide (MESH:D013449), ester (MESH:D004952), amine (MESH:D000588), ATP (MESH:D000255), benzyl chloride (MESH:C021292), Symdeko (MESH:C000654124), indoles (MESH:D007211), carbodiimide (MESH:D002234), disulfide (MESH:D004220), Rucaparib (MESH:C531549), Bortezomib (MESH:D000069286), trabectedin (MESH:D000077606), Mobocertinib (MESH:C000720862), acid (MESH:D000143), Uprifosbuvir (MESH:C000627758), acetic anhydride (MESH:C031800), phosphine (MESH:C044646), Lurbinectedin (MESH:C568606), Grazoprevir (MESH:C578009), halogen (MESH:D006219), Chloride (MESH:D002712), Tezacaftor (MESH:C000625213), Osimertinib (MESH:C000596361), Gefitinib (MESH:D000077156), Macimorelin (MESH:C582727), Bazedoxifene (MESH:C447119), N-bromosuccinimide (MESH:D001974), serotonin (MESH:D012701), hydroxyl (MESH:D017665), hydrogen (MESH:D006859), Nintedanib (MESH:C530716), alkaloids (MESH:D000470), Piperidine (MESH:C032727), tert-butyldimethylsilyl (TBS) chloride (MESH:C404749), alcohol (MESH:D000438), hydroxamic acid (MESH:D006877), Farydak (MESH:D000077767), AlCl3 (MESH:D000077410), nitrogen (MESH:D009584), Ruzasvir (MESH:C000621654), imidazole (MESH:C029899), TEMPO (MESH:C003959), amide (MESH:D000577), amino acid (MESH:D000596), salt (MESH:D012492), taxanes (MESH:D043823), Erlotinib (MESH:D000069347), hydrochloric acid (MESH:D006851), tryptophan (MESH:D014364), platinum (MESH:D010984), methanol (MESH:D000432), Flortaucipir (MESH:C000591008), benzyl ether (MESH:C076624), glucose (MESH:D005947), Etrasimod (MESH:C000656249)
- **Species:** Cercopithecidae (monkey, family) [taxon 9527], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Canis lupus familiaris (dog, subspecies) [taxon 9615]
- **Mutations:** L858R, F508del, T790M
- **Cell lines:** Lurb-001 — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_B4K8)

## Figures

18 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12854230/full.md

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Source: https://tomesphere.com/paper/PMC12854230