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Drug Library

Recommended article: 【Chemoinformatics】 Material library

1. Overview

2. Low molecular weight drugs

3. Antibody Drugs

4. Nucleic Acid Treatment

5. Nanopharmaceuticals

6. Cell therapy

7. Radioactive agents

8. Next Generation Drugs

9. Examples of drugs according to cancer types

a. Drug class library

b. Pharmacology

c. Drug synergy modeling

1. Overview

⑴ Molecular representation

① Structure-based

○ Pattern-based FP: MACCS, PubChem, FP3, FP4

② Topological

○ Path-based FP: Daylight, FP2

○ Circular FP: ECFP2, ECFP4, ECFP6

○ Pharmacophore FP: 2D pharamacophore

③ Neural-network-based

○ Graph-based representation: GNN; graph convolutional network (GCN), graph attention network (GAT), gated graph neural network (GGNN)

○ Molecular embedding: seq2seq, mol2vec

⑵ Drug trends

① First-Generation Therapies: Chemotherapy, Radiotherapy (Complexity ↓↓)

○ Drug Efficacy Assessment: In vitro models (cancer cell lines)

○ Mechanism of Action (MoA) / Proof of Concept (PoC): Direct inhibition

② Second-Generation Therapies: Targeted Therapy (Complexity ↓)

○ Drug Efficacy Assessment: Mutation models (PDX, PDC)

○ Mechanism of Action (MoA) / Proof of Concept (PoC): Direct inhibition

○ Clinical Biomarkers: Mutations (cfDNA, WES, TES)

③ Third-Generation Therapies: Immunotherapy (Complexity ↑)

○ Drug Efficacy Assessment: TMB, TIL, TPS, MSI, Neoantigen

○ Mechanism of Action (MoA) / Proof of Concept (PoC): CTL / Macrophages, NK/B/MDSC/Treg, Stroma

○ Clinical Biomarkers: Blood (PBMC, Cytokines), Immune Score

④ Fourth-Generation Therapies: Microbiome / Metabolism (Complexity ↑↑)

○ Drug Efficacy Assessment: Microbiome, TMB, TIL, TPS, MSI, Neoantigen

○ Mechanism of Action (MoA) / Proof of Concept (PoC): CTL / Macrophages, NK/B/MDSC/Treg, Stroma, Microbiome, Metabolites

○ Clinical Biomarkers: Blood (PBMC, Cytokines), Immune Score, Microbiome, Metabolites

⑤ Recent Drug Trends: Increased drug size, increased fat solubility (clogP)This is contrary to Ripinsky’s rule of 5.

⑶ Drug screening technology

① Affymetrix GeneChip: HG-U133 Plus 2.0 Array, etc.

② Luminex bead arrays (L1000)

○ Level 1. Raw (LXB): 978 landmark genes only

○ Level 2. GEX: 978 landmark genes only

○ Level 3a. NORM: 12,328 genes (978개의 landmark + 11,350 inferred)

○ Level 3b. INF: 12,328 genes (978개의 landmark + 11,350 inferred)

○ Level 4. ZS (z-scoring): 12,328 genes (978개의 landmark + 11,350 inferred)

○ Level 5. MODZ (moderate z-score)

○ Analysis: WTCS(weighted connectivity score)의 계산, NCS(normalized connectivity score), Tau

③ Illumina Human HT-12 v4 Expression BeadChip Array

④ mRNA-seq (Illumina Hi-Seq)

⑤ GCP: histone profiling

⑥ P100: phosphoproteomics

⑦ KINOMEscan

⑧ KiNativ

⑨ MEMA

⑩ ELISA

⑪ RPPA

⑫ ATAC-seq

⑬ Cellarium

⑭ SWATH-MS

2. Small Molecule Drugs

○ Overview

① -nib suffix: In the smallmoleculeinhibitor, abbreviate “inhibit” to -nib

○ 4-aminopyridine (4-AP): A voltage-dependent potassium channel blocker

○ Abemaciclib: CDK4/CDK6 inhibitor

○ Abiraterone acetate: A CYP17A1 inhibitor. Reduces PSA.

○ Adagarasib: KRAS G^12C inhibitor

○ Afatinib (BIBW2992): EGFR inhibitor

○ Afuresertib: pan-AKT inhibitor

○ Alectinib: Tyrosine kinase inhibitor

○ Alexidine: Targeting DDR2

○ AMD3100: CXCR4 inhibitor

○ AMPA: An agonist for AMPA type glutamate receptor

○ AP5: A competitive antagonist for NMDA receptors

○ Asras tablet

① circular purification of microsulfur nuclei

② Nonsteroidal antipyretic, anti-inflammatory (inflammatory relief), painkillers

③ Store in airtight container at room temperature (1-30℃)

○ Atebimetinib: MEK inhibitor

○ AVL-292: BTK inhibitor

○ Axitinib: VEGFR  inhibitor 

○ Ayvakit: Avapritinib; PDGFRa; signaling/kinase; GIST; FDA-approved in 2020

○ AZ138: Eg5 inhibitor

○ Azacytidine: DNA methylation inhibitor

○ AZD7762: CHEK1/2 inhibitor

○ Balversa: Erdafitinib; FGFR2/3; signaling/kinase; bladder cancer; FDA-approved in 2019

○ BAY73-4506: Blockade of RAF

○ Benfluorex: Withdrawn due to cardiovascular side effects

○ Bicuculline methiodide: GABA_A receptor antagonist

○ Binimetinib: an inhibitor of MEK1 and MEK2, key kinases in the RAS–RAF–MEK–ERK signaling pathway. By inhibiting MEK1/2, binimetinib prevents the activation of ERK (extracellular signal-regulated kinase), thereby blocking downstream signaling that promotes cell proliferation and survival.

○ Bleomycin: Induces lung injury.

○ Bosutinib: BCR-ABL inhibitor

○ cAMP phosphodiesterase: cAMP inhibitor

○ Canertinib: EGFR/HER inhibitor

○ Cannabanine

① A large amount is present in the seeds of Canavalia eniformis.

② Substances very similar in structure to the amino acid arginine.

③ Non-protein amino acids that are not expressed in living proteins, and arginine-filled enzymes in herbivores cannot distinguish arginine from cannabanine, producing tRNA linked to cannabanine instead of arginine.

④ Canabanin is inserted into protein instead of arginine, resulting in the deformation of the tertiary structure of the protein, which makes it impossible to function normally, and the larvae of herbivores who ate it die.

○ Capillin: fungicide

○ (R)-(-)-carvone: spearmint oil

○ (S)-(+)-carvone: caraway seed oil

○ CGM097: Targeting MDM2 mutant form specifically

○ CGP55845: GABA_B receptor blocker

○ CHIR99021: GSK3inhibitor, WNT activator

○ Ciliobrevin D: inhibitor of degranulation of NK cells

○ Cinnamaldehyde: cinnamon flavoring

○ Cisplatin: FAP inhibitor

○ CNQX: A competitive antagonist for non-NMDA receptor

○ CNX-774: BTK inhibitor

○ COH34: PARG inhibitor

○ Crizotinib

① A receptor tyrosine kinase inhibitor and ROS1 inhibitor primarily used for NSCLC (Non-Small Cell Lung Cancer).

② The drug was approved by the FDA in 2021 and is also used for colorectal cancer.

○ Cyclosporine A: widely used in dry eye syndrome treatment

○ Dapansutrile: NLRP3 phase-2 inhibitor

○ DAPT: Notch inhibitor 

○ Dasatinib: BCR-ABL inhibitor

○ Decitabine: DNMT inhibitor (DNA methylation inhibitor)

○ Deoxycholic acid: Component of subsequent fat removal injection. trademark name is Kybella

○ Demecolcine: Microtubule destabilizing agent

○ DES (Diethylstilbestrol)

① drug for preventing pregnant failure prescribed between 1938 and 1971

② Estrogen simulation causes abnormalities in fetal uterine development: 24% of daughters born are infertile

③ Synthetic female hormone without steroid backbone

④ Prohibition of the use of backtracking research results by 20,000 women

○ Dexamethasone: Can penetrate BBB.

○ DiABZI 3: STING1 agonist

○ Diazinon: insect repellent

○ Digoxin: blocks a protein channel that helps cells cohere, used for the heart disease medication.

○ DM1: microtubule inhibitor

○ DMF(Dimethyl fumarate): an immunomodulatory drug that activates the Nrf2 (nuclear factor erythroid 2–related factor 2) pathway via covalent modification of the cysteine residues on Keap1, the cytosolic protein that normally binds Nrf2 and targets it for degradation. By oxidizing or alkylating the thiol groups of Keap1, DMF destabilizes the Keap1–Nrf2 complex, allowing Nrf2 to escape ubiquitination and translocate into the nucleus. In parallel, DMF also inhibits NFκB mediated transcription.

○ DNQX: AMPA receptor antagonist

○ Dopa: A treatment for Parkinson’s disease, is effective in its L-form only.

○ Doxycyclin: be used as an anticancer drug

○ enasidenib (Celgene) : mIDH inhibitor

○ Enediyne: anti-cancer drug

○ Erdafitinib (Erda): Tyrosine kinase (e.g., FGFR) inhibitor

○ Erivedge: Vismodegib; SMO (Hedgehog pathway); GPCR; basal cell carcinoma; FDA-approved in 2012

○ Erlotinib (Tarceva): EGFR inhibitor

○ Esomeprazole: proton pump inhibitor, digestive medicine

○ Eulexin: Flutamide, non-steroidal; androgen receptor; nuclear receptor; prostate cancer; FDA-approved in 1989

○ Fillipin: removes cholesterol from the cellular membrane

○ Finerenone

① NR3C2 antagonist

② FDA approval for CKD (chronic kidney disease) treatment in 2021

○ Gabazine: GABA_A receptor antagonist

○ Galunisertib (LY21577299) : TGF-βR1 inhibitor

○ Gardine tablet

① lanitidine hydrochloride H² blockers and gastric acid secretion inhibitors

② Prevention and treatment for gastric ulcer, duodenal ulcer, gastroesophageal reflux disease

○ Gefitinib (Iressa): Anti-cancer drugs that inhibit EGFR-TKI (EGFR-tyrosine kinase inhibitor). FDA Approved

○ Gemcitabine

① first line drug of pancreatic cancer

② pyrimidine antimetabolite

○ Gleevec: Imatinib: ABL; signaling/kinase; CML, ALL; FDA-approved in 2001

○ GSK690693: blockade of AKT

○ 4-hydroxybutanoic acid: a so-called mulberry drug

○ Ibotenic acid

① Compounds found in clown mushrooms and devil clown mushrooms

② If you eat a lot, you will have hallucinations.

○ Ibrance: Palbocicllib; CDK4/6; signaling/kinase; HR+/HER2- breast cancer; FDA-approved in 2015

○ Ibrutinib

① It targets Bruton’s tyrosine kinase (BTK) irreversibly.

② FDA approved for mantle cell lymphoma, chronic lymphocytic leukemia, and multiple hematological malignancy.

○ Ichthyothereol: convulsant

○ Idhifa: Enasidenib; IDH2; epigenetic/metabolism; AML; FDA-approved in 2017

○ IM2C6: VEGFR inhibitor 

○ Imatinib: Small molecule kinase inhibitor

○ Imbruvica: Ibrutinib; BTK; signaling/kinase; mantle cell lymphoma, CLL; FDA-approved in 2013

○ Iressa: gefitinib; EGFR; signaling/kinase; NSCLC, breast; FDA-approved in 2003

○ (-)-iridomyrmecin: compounds released when ants try to protect themselves from predators

○ Ispinesib: Specifically inhibits Kinesin spindle protein (KSP)

○ ITX-5061: Antagonist of SCARB1

○ ivosidenib (Agio): mIDH inhibitor

○ IWR-1-endo (Calbiochem): Wnt inhibitor

○ JQ1: BRD2, BRD3, BRD4, BRDT inhibitor

○ JT010: TRPA1 agonist

○ Kainic acid: An agonist for both kainate and AMPA glutamate receptors

○ KIRA6: IRE1α inhibitor

○ Kyn: An ionotropic glutamate receptor antagonist

○ Lapatinib (Tyverb): Inhibits the TKD, thereby directly suppressing downstream signaling. FDA-approved.

○ Lobeglitazone (Lobe)

① antiatherogenic drug

② promotes cholesterol efflux (through PPARγ activation & LXRα, ABCA1, and ABCG1 dependent pathways)

○ Losartan: angiotensin inhibitor

○ Loxonin: Painkillers

○ Lumakras: Sotorasib; KRAS; signaling; NSCLC; FDA-approved in 2021

○ Lutathera: Lutetium Lu177 dotatate; somatostatin receptor; GPCR; GEP-NETs; FDA-approved in 2018

○ LY-294002: Classical PI3K inhibitor

○ Lynparza: Olaparib; PARP Inh; DNA repair; ovarian, breast, prostate, pancreatic; FDA-approved in 2014

○ Mavorixafor: CXCR4 inhibitor

○ Mekinist: Trametinib; MEK; signaling/kinase; melanoma; FDA-approved in 2013

○ Met-enkephalin: Opioid receptor agonist

○ Metformin: Anti-diabetic drug (1959)

○ (S)-methamphetamine:illegal // (R)-methamphetamine:legal

○ MG132: proteasome inhibitor

○ Mivobulin isethionate: Colchicine analog. Also a microtubule targeting agent.

○ MK801: A NMDA receptor open-channel blocker. The non-competitive NMDA receptor antagonist

○ ML210: GPX4 inhibitor

○ MMAE(monomethyl auristatin E): Tubulin polymerization inhibitor

○ MSA-2: STING1 agonist

○ Nandrolone: anabolic steroids illegally used by athletes to strengthen their muscles

○ NCS23766: Rac1 inhibitor

○ NEM(N-ethylmaleimide): chemical that binds to myosin and inhibits its function

○ Niclosamide: anthelminthic drug

○ Nilotinib: BCR-ABL inhibitor

○ NMDA: An agonist for NMDA receptor

○ Ogumentin tablet

① white or nearly white oval

② Penicillin antibiotic used for bacterial infections

③ Store in airtight container (moisturizing packaging) at 1-25°C

④ Be careful of constipation and dizziness

○ OKN4395: Owkin first‑in‑class EP2/EP4/DP1 inhibitor

○ Olaparib: PARP inhibitor

○ Orgovyx: Relugolix; GnRH receptor; GPCR; prostate cancer; FDA-approved in 2020

○ Osimertinib (Tagrisso): EGFR inhibitor

○ Ouabain: Cardiac glycoside, Na/K-ATPase inhibitor. Plant-derived and was used as an arrow poison for both hunting and warfare.

○ Pacritinib: an oral tyrosine kinase inhibitor that selectively targets JAK2 and FLT3 kinases. By blocking JAK2’s kinase activity, pacritinib suppresses the overactive JAK-STAT signaling that drives pathogenic cell proliferation and cytokine production in diseases such as myelofibrosis. It also inhibits growth signaling pathways.

○ Palbociclib

○ An FDA-approved treatment for breast cancer.

○ It selectively inhibits cyclin-dependent kinases CDK4 and CDK6.

○ Panobinostat: pan‐HDAC inhibitor

○ Pazopanib: VEGFR inhibitor 

○ PD0325901: MEK inhibitor

○ PD173074: specific VEGFR inhibitor

○ PDD00017272: PARG inhibitor

○ PF7845-yne: Fatty acid amide hydrolase (FAAH) inhibitor

○ Phalloidin: Targeting actin filament

○ Piqray: Idelalisib; PI3Ka, PI3Kd; signaling/kinase; HR+ HER2- breast cancer, CLL, blood cancer; FDA-approved in 2019

○ PP2: Tyrosine kinase inhibitor

○ Pralsetinib: a selective Ret proto-oncogene (RET) kinase inhibitor. Known to target 11 key proteins: RET, DDR1, NTRK3, fms-related receptor tyrosine kinase 3 (FLT3), JAK1, JAK2, NTRK1, KDR, platelet derived growth factor receptor-β (PDGFRB), fibroblast growth factor receptor 1 (FGFR1) and FGFR2.

○ PX478: HIF1a inhibitor

○ Quizartinib: hERG inhibitor

○ Rapamycin: Sirolimus, Rapamune; mTOR; signaling; RCC; FDA-approved in 1999; anti-fungal agent (1975)

○ Rentosertib: TNIK inhibitor

○ Retevmo: Selpercatinib; RET; signaling/kinase; NSCLC, thyroid cancer; FDA-approved in 2020

○ RGFP966: Targeting GATA2

○ Ricin: ribosome-inactivating protein created by Ricinus communis

○ RSL3: GPX4 inhibitor

○ Rydapt: Midostaurin; FLT3; signaling/kinase; AML; FDA-approved in 2017

○ S1 nuclease: Hydrolyze all of the nucleic acid endotransferase, single-stranded DNA, or RNA isolated from Aspergillus aurizae

○ Sapitinib

○ SB216763: GSK-3 inhibitor 

○ SB431542 (Stemgent): TGF-β inhibitor

○ Silmitasertib(CX-4945): Kinase CK2 inhibitor

○ SN-38: An inhibitor of topoisomerase I. Active metabolite of irinotecan.

○ Sorafenib: Antiangiogenic treatment, multikinase inhibitor

○ Sotorasib: FDA approval for KRAS^G12C non-small-cell lung canceller

○ SP600125: blockade of JNK

○ SR95531: GABA_A receptor blocker

○ Sunitinib: VEGFR  inhibitor 

○ Sutent: Sunitinib; VEGFR; signaling/kinase; solid cancers; FDA-approved in 2006

○ T-5224: c-FOS inhibitor 

○ Tabrecta: Capmetinib; MET; signaling/kinase; NSCLC; FDA approved in 2020

○ Talabostat: FAP inhibitor

○ Tazemetostat: EZH2 inhibitor

○ Tazverik: Tazemotostat; EZH2; epigenetics; epitheliod sarcoma, follicular lymphoma; FDA-approved in 2020

○ TBOA

○ A competitive antagonist for glutamate transporters

○ Has at least one hydrophobic benzyl group larger than glutamate

○ TBOA mimics glutamate in potentiating GABA_A-receptor-mediated responses

○ Tepoxalin: It specifically kills cells with high ABCB1 expression.

○ Tibsovo: Ivosldenib; IDH1; epigenetic/metabolism; AML; FDA-approved in 2018

○ Tirofiban: Glycoprotein IIb/IIIa receptor inhibitor.

○ Toxane: microtubule toxin

○ Tramol tablet

① white circular tablet

② Lower fever and reduce pain as antipyretic drugs

③ Stored at room temperature (1-30℃) in an airtight container

○ Transgelin: smooth muscle marker

○ Trifluralin B: non-selective herbicide.

○ TTX: A voltage-dependent sodium channel blocker

○ Turalio: Pexidartnib; CSF1R, KIT, FLT3; signaling/kinase; symptomatic tenosynovial giant cell tumor; FDA-approved in 2019

○ Tykerb: Lapatinib; Her2; signaling/kinase; breast; FDA-approved in 2007

○ Unifectan capsule

① upper green and lower yellow capsules containing white powder

② Easy discharge of sputum with sputum solubilizer

③ Store in airtight container at room temperature (1-30℃)

④ Beware of dizziness

○ Vanadium: It specifically kills cells with high SLC26A2 expression.

○ Vanillin: Vanilla flavoring.

○ Vemurafenib: the first approved BRAF inhibitor for melanoma

○ Venclecta: Venetoclax; BCL2; apoptosis; CLL, AML; FDA-approved in 2016

○ Venetoclax: BCL-2 inhibitor

○ Vismodegib: SHH inhibitor

○ Vitrakvl: Larotrectinib; TRK; signaling/kinase; solid tumors w/ NTRK gene fusion; FDA-approved in 2018

○ Vorinostat: α histone deacetylase inhibitor used to treat cutaneous T cell lymphoma.

○ VS-4718: FAK inhibitor

○ WAY100635: 5HT1A receptor antagonist

○ Wortmannin: PI3K inhibitor

○ Xalkorl: Crizotinib; ROS1; signaling/kinase; NSCLC; FDA-approved in 2016

○ Xpovlo: Selinexor; XPO1; nuclear export; MM; FDA-approved in 2019

○ Y-27632: ROCK inhibitor

○ Z-DEVD-FMK: Caspase 3 inhibitor 

○ Zelboraf: Vemurafenib; BRAF; signaling/kinase; melanoma; FDA-approved in 2011

○ Zoldonrasib: RAS(ON) inhibitor

○ Zolinza: Volinostat; HDAC; epigenetics; cutaneous T-cell lymphoma; FDA-approved in 2006

○ Zydellg: Alpellsib; PI3Ka, PI3Kd; signaling/kinase; HR+ HER2- breast cancer, CLL, blood cancer; FDA-approved in 2014

Table 1. Kratom alkaloid

3. Antibody Drugs

⑴ Overview

① Since antibodies themselves are large, only a part of them are generally used as drugs.

○ VH

○ Fab

○ scFv

○ diabody

○ scFv-Fc

○ scFv-CH

○ scFab

○ scFv-zipper

② Humanization should be performed to prevent antibody drugs from triggering immune responses in the human body.

○ Types of humanization: mab means monoclonal anibody

○ -omab: murine (0% human).ability to act as an antigen in humans

○ -ximab: chimeric (65% human)

○ -zumab: humanized (＞ 90% human)

○ -umab: fully human (100% human)

○ humanization method

○ phage display

○ transgenic mouse

③ Antibody drugs last long in the blood, so you can prescribe them from time to time.

⑵ General Antibody Drugs: be labeled as “antigen:antibody”

○ B7-H3: enoblituzumab, ifinatamab deruxtecan (B7-H3–targeted ADC), elfetabart drozuntecan, ifinatamab deruxtecan, risvutatug rezetecan, MHB088C, tambotatug pelitecan

○ B7-H4: puxitatug samrotecan, mocertatug rezetecan

○ BCMA: belantamab mafodotin

○ cadherin-6: raludotatug deruxtecan

○ CAIX: cG250

○ CD19: loncastuximab tesirine, monjuvi (tafasitamab; immune; DLBCL; FDA-approved in 2020)

○ CD20: rituxan (rituximab; immune; NHL, CLL; FDA-approved in 1997), ibritumomab tiuxetan, tositumomab

○ CD22: inotuzumab ozogamicin

○ CD3: CD8 T cell activator

○ CD3/CD28: CD4 T cell activator

○ CD30: brentuximab vedotin

○ CD33: gemtuzumab ozogamicin, BL-M11D1

○ CD38: darzalex (daratumumab; immune; MM; FDA-approved in 2015)

○ CD4/8: T cell depletion

○ CD52: lemtrada (alemtuzumab; immune; CML; FDA-approved in 2001)

○ CD79b: polatuzumab vedotin, SHR-A1912

○ CD123: pivekimab sunirine

○ CEA: labetuzumab

○ claudin6: ixotatug vedodin

○ claudin18.2: sonesitatug vedotin, tecotabart vedotin, arcotatug tavatecan, JS107, garetatug rezetecan, XNW27011, ASP546C

○ cMET: telisotuzumab, MYTX-011, telisotuzumab adizutecan

○ CTLA4: yervoy (ipilimumab; immune; various cancers; FDA-approved in 2011), botensilimab

○ DLL3: zocilurtatug pelitecan

○ EGFR: cetuximab (erbitux; signaling; colorectal cancer, NSCLC; FDA-approved in 2004), panitumumab, nimotuzumab, 806, MCLA-158 (petosemtamab), izalontamab brengitecan, becotatug vedotin, CPO301, SYS6010

○ EpCAM: IGN101, adecatumumab

○ EPHA3: KB004, IIIA4

○ ERBB2: trastuzumab, pertuzumab

○ Trastuzumab is the only drug for glioblastoma.

○ 98% of small molecule drug is suppressed by close connection of brain capillaries.

○ ERBB3: MM-121

○ FAP: sibrotuzumab, F19

○ folate binding protein: MOv18, MORAb-003 (farletuzumab)

○ FRα (folate receptor α): mirvetuximab soravtansine with DM4, torvutatug samrotecan, onvontatug videtecan, rinatabart sesutecan, sofetabart mipitecan

○ fusion protein of RSV : palivizumab

○ ganglioside (e.g., GD2, GD3, GM2): 3F8, ch14.18, KW-2871

○ GD2: Unituxin (dinutuximab; ADCC/CDC; neuroblastoma; FDA-approved in 2015)

○ gpA33: huA33

○ GP IIb/IIIa: abciximab

○ HER2: margetuximab (monoclonal antibody), herceptin (trastuzumab; signaling; breast cancer, gastric, GEJ cancer; FDA-approved in 1998)

○ HER3: izalontamab brengitecan, beruzatatug pelitecan, ruzaltatug rezetecan, patritumab deruxtecan

○ IFNAR1: Anifrolumab (IFNAR1 antagonist. FDA approval for SLE (Systemic Lupus erythematosus) treatment in 2021)

○ IGF1R: AVE1642, IMC-A12, MK-0646, R1507, CP751871

○ IL-4R: Dupilumab, a treatment for atopic dermatitis, binds to the target called IL-4R and inhibits the secretion of IL-4R.

○ IL-6R: tocilizumab is anti-IL-6R humanized monoclonal antibody

○ integrin α4β1: natalizumab (approved for treating multiple sclerosis and Crohn disease)

○ integrin α5β1: volociximab

○ integrin αVβ3: etaracizumab

○ integrin β6: sigvotatug vedotin

○ Leγ: hu3S193, IgN311

○ MET: AMG102, METMAB, SCH900105

○ microtubule: enfortumab vedotin

○ MUC16: sofituzumab, DMUC4064A

○ mucin: pemtumomab, oregovomab

○ NECTIN4: enfortumab vedotin, sutantatug envedotin, bulumtatug fuvedotin, notiretatug rezetecan

○ OSMR_β: Vixarelimab (a first-in-class, human monoclonal antibody engineered to block OSMR_β-mediated signaling while preserving the LIFR pathway)

○ PD-1: XMT-2056, nivolumab (first approval in 2014 for melanoma), keytruda (pembrolizumab; immune; various cancers; FDA-approved in 2014), balstilimab

○ PD-L1: tecentriq (atezolizumab; immune; various cancers; FDA-approved in 2016), fetrastobart vedotin

○ PDGFRα: Lartruvo (olaratumab; signaling; soft tissue sarcoma; FDA-approved in 2016)

○ PSMA: J591

○ RANKL: denosumab

○ ROR1: zilovertamab vedotin

○ SEZ6: turmetabart adizutecan

○ SLAMF7: Empliciti (elotuzumab; immune; MM; FDA-approved in 2015)

○ TAG-72: CC49 (minretumomab)

○ Tenascin: 81C6

○ TNF: Adalimumabm, Infliximab

○ Topoisomerase I: Trastuzumab Deruxtecan, Sacituzumab Govitecan (having SN-38 as payload)

○ TRAILR1: mapatumumab (HGS-ETR1)

○ TRAILR2: HGS-ETR2, CS-1008

○ TROP2: sacituzumab govitecan with SN-38, datopotamab deruxtecan, sacituzumab tirumotecan, FDA018, OQY-3258, ESG-401, STI-3258, tizetatug rezetecan

○ VEGF: ranibizumab, aflibercept, bevacizumab

○ VEGFA: Avastin (bevacizumab; signaling; colorectal cancer; FDA-approved in 2004)

○ VEGFR: CDP791

○ VEGFR2: Cyramza (ramucirumab; signaling; gastric cancer; FDA-approved in 2014)

⑶ Bispecific antibody: be labeled as “antigen:antibody”

○ CD3/CD19: Blincyto (Blinatumomab; bi-specific Ab; ALL; FDA-approved in 2014)

○ CD3/CD20: Glofitamab (RG6026; bi-specific Ab; DLBCL; P3), Mosunetuzumab (RG7828; bi-specific Ab; FL; P3 (BTD))

○ EGFR/cMET: Rybrevant (Amivantamab; bi-specific Ab; NSCLC; FDA-approved in 2021)

○ PD-1/Lag3: Tebotelimab (Bi-specific Ab; gastric, GEJ; P3)

⑷ Antibody drug conjugate (ADC): be labeled as “antigen:antibody”

○ BMCA: Blenrep (Belantamab-mefodotinf; ADC; MM; FDA-approved in 2020)

○ CD19: Zynlonta (Ioncastuximab-tesirine; ADC; DLBCL; FDA-approved in 2021)

○ CD22: Besponsa (Inotuzumab-ozogamicin; ADC; ALL, hairy cell leukemia; FDA-approved in 2017)

○ CD30: Adcetris (Brentuximab-vedotin; ADC; hodgkin lympoma, systemic anaplastic, large cell lymphoma; FDA-approved in 2011)

○ CD33: Mylotarg (Gemtuzumab-ozogamicin; ADC; AML; 2000, FDA-approved in 2017)

○ CD76β: Polivy (Polatuzumab-vedotin; ADC; DLBCL; FDA-approved in 2019)

○ HER2: kadcyla (trastuzumab-emtansine; ADC; breast cancer; FDA-approved in 2012), disitamab vedotin, trastuzumab botidotin, trastuzumab deruxtecan, trastuzumab rezetecan, rolditamig deuderuxtecan, anvatabart opadotin, trastuzumab brengitecan, trastuzumab pamirtecan, trastuzumab envedotin, GQ1005, trastuzumab bultecan, caxmotabart entudotin, anbenitamab repodatecan, trastuzumab vedotin

○ Nectin4: Padcev (Enfortumab-vedotin; ADC; bladder cancer; FDA-approved in 2019)

○ Trop2: Trodelvy (Sacituzumab-govitecan; ADC; TNBC; FDA-approved in 2020)

Table 2. Clinically approved antibody–drug conjugates

⑸ TCE(T cell engager)

○ Blinatumomab: Bispecific T cell engager

○ Glofitamab: Bispecific T cell engager

○ Mosunetuzumab: Bispecific T cell engager

○ Tarlatamab: Used for the treatment of small cell lung cancer, is currently the only TCE that has achieved clinical proof of concept in solid tumors.

○ Teclistamab: Bispecific T cell engager

4. Nucleic Acid Treatment

⑴ Type 1. siRNA

⑵ Type 2. Nucleic Acid Nanopharmaceuticals: DNA aptamer, DNA origami, etc.

5. Nanopharmaceuticals

⑴ Overview

① Advantages: Design is possible. Various functions can be given through surface modification.ease of introduction of concomitant drugs

② Disadvantages: Difficulty in mass production.It can break down in vivo and cause toxicity or side effects

⑵ Type 1. Liposome

⑶ Type 2. IONP (iron oxide nanoparticle)

⑷ Type 3. MSNP (mesoporous silica nanoparticle)

⑸ Type 4. Nucleic acid nanopharmaceuticals: DNA aptamer, DNA orgami, etc.

⑹ Type 5. LNP: In vivo unstable siRNA, mRNA, etc. delivered to target

① ALC-0315 (Pfizer/BioNTech)

② SM-102 (Moderna)

③ ALC-0159 (Pfizer/BioNTech)

④ PEG-DMG (Moderna)

6. Cell Therapy

⑴ Overview

① Advantages

○ Design is possible.

○ It can utilize cell-specific functions such as crossing BBB or supplementing defective tissues.

② Disadvantages

○ low yield and low repeatability

○ Cells that are therapeutic must survive

○ The high cost

○ It can also form tumors.

③ Cell therapy works well for blood cancer, but not for solid cancer.

⑵ Type 1. CAR(chimeric antigen receptor)-T cell therapy

① 1^st. Extract T cell from patient’s blood

② 2^nd. Inject the inactive virus into the T cell to express an engineered receptor.

③ 3^rd. GROWTH TO MILLIONS OF CELL

④ 4^th. Injection into the patient’s body → Cancer treatment

⑤ Blood cancer is treated well, but solid cancer is not treated well.

○ Reason: Unlike blood cancer, tumor microenvironment of solid cancer reduces CAR-T activity.

⑥ Currently, there are five CAR-T FDA approved drugs.

○ Tisagenlecleucel (Kymriah; CD19; CAR-T; DLBCL, FL, ALL, MCL): FDA-approved in 2017

○ Axicabtagene ciloleucel (Yescarta): FDA-approved in 2017

○ Brexucabtagene autoleucel (Tecartus): FDA-approved in 2020

○ Lisocabtagene maraleucel (Breyanzi): FDA-approved in 2021

○ Iidecabtagene vicleucel (Abecma; BCMA; CAR-T; MM): FDA-approved in 2021

⑶ Type 2. Sipuleucel-T

① Examples of Cancer vacine for treatment

② 1^st. Extract antigen-presenting cells (APCs) from patients

③ 2^nd. Exposurend of antigen to antigen-presenting cells in vitro

④ 3^rd. Infuse the learned antigen-presenting cells back into the patient

⑤ Used to treat prostate cancer

⑥ Advantages of being able to provide one-on-one customized treatment

⑷ Type 3. Stem cell therapy

⑸ Type 4. Microbial treatment

7. Radioactive Drugs

⑴ ¹⁸F-FDG has fewer side effects: it uses fewer substances.

8. Next Generation Drugs

⑴ small molecule

① small molecule

② PROTAC

③ zirconium cyclosilicate

⑵ antibody therapeutic

① monoclonal antibody

② antibody drug conjugate

③ bispecific antibody

④ fragment antibody

⑶ peptide or protein therapeutic

① therapeutic protein

② bicyclic peptide

③ anticalin® protein

⑷ nucleotide-based therapeutic

① antisense oligonucleotide

② oligonucleotide conjugate

③ small interfering RNA

④ mRNA

⑤ therapeutic gene editing

⑸ cell-based therapeutic

⑹ IVEB(in vivo expressed biologics)

9. Examples of drugs according to cancer types

⑴ Lymphoma (30)

○ Ibritumomab tiuxetan (ZevalinⓇ), Denileukin diftitox (OntakⓇ), Brentuximab vedotin (AdcetrisⓇ), Rituximab (RituxanⓇ), Vorinostat (ZolinzaⓇ), Romidepsin (IstodaxⓇ), Bexarotene (TargretinⓇ), Bortezomib (VelcadeⓇ), Pralatrexate (FolotynⓇ), Ibrutinib (ImbruvicaⓇ), Siltuximab (SylvantⓇ), Idelalisib (ZydeligⓇ), Belinostat (BeleodaqⓇ), Obinutuzumab (GazyvaⓇ), Nivolumab (OpdivoⓇ), Pembrolizumab (KeytrudaⓇ), Rituximab & Hyaluronidase human (Rituxan Hycela™), Copanlisib hydrochloride (Aliqopa™), Axicabtagene ciloleucel (Yescarta™), Acalabrutinib (CalquenceⓇ), Tisagenlecleucel (KymriahⓇ), Venetoclax (Venclexta™), Mogamulizumab-kpkc (PoteligeoⓇ), Duvelisib (Copiktra™), Polatuzumab vedotin-piiq (Polivy™), Zanubrutinib (Brukinsa™), Tazemetostat hydrobromide (Tazverik™), Selinexor (Xpovio™), Tafasitamab-cxix (MonjuviⓇ), Brexucabtagene autoleucel (Tecartus™)

⑵ Leukemia (27)

○ Tretinoin (VesanoidⓇ), Imatinib mesylate (GleevecⓇ), Dasatinib (SprycelⓇ), Nilotinib (TasignaⓇ), Bosutinib (BosulifⓇ), Rituximab (RituxanⓇ), Alemtuzumab (CampathⓇ), Ofatumumab (ArzerraⓇ), Obinutuzumab (GazyvaⓇ), Ibrutinib (ImbruvicaⓇ), Idelalisib (ZydeligⓇ), Blinatumomab (BlincytoⓇ), Venetoclax (Vendexta™), Ponatinib hydrochloride (IclusigⓇ), Midostaurin (RydaptⓇ), Enasidenib mesylate (IdhifaⓇ), Inotuzumab ozogamicin (BesponsaⓇ), Tisagenledeucel (KymriahⓇ), Gemtuzumab ozogamicin (Mylotarg™), Rituximab & Hyaluronidase human (Rituxan Hycela™), Ivosidenib (TibsovoⓇ), Duvelisib (Copiktra™), Moxetumomab pasudotox-tdfk (Lumoxiti™), Glasdegib maleate (Daurismo™), Gilteritinib (XospataⓇ), Tagraxofusp-erzs (Elzonris™), Acalabrutinib (CalquenceⓇ)

⑶ Breast (25)

○ Everolimus (AfinitorⓇ), Tamoxifen (Nolvadex), Toremifene (FarestonⓇ), Trastuzumab (HerceptinⓇ), Fulvestrant (FaslodexⓇ), Anastrozole (ArimidexⓇ), Exemestane (AromasinⓇ), Lapatinib (TykerbⓇ), Letrozole (FemaraⓇ), Pertuzumab (PerjetaⓇ), Ado-trastuzumab emtansine (KadcylaⓇ), Palbociclib (IbranceⓇ), Ribociclib (KisqaliⓇ), Neratinib maleate (Nerlynx™), Abemaciclib (Verzenio™), Olaparib (Lynparza™), Talazoparib tosylate (TalzennaⓇ), Atezolizumab (TecentriqⓇ), Alpelisib (PiqrayⓇ), Fam-trastuzumab deruxtecan-nxki (EnhertuⓇ), Tucatinib (Tukysa™), Sacituzumab govitecan-hziy (Trodelvy™), Pertuzumab, Trastuzumab, Hyaluronidase–zzxf (Phesgo™)

⑷ Lung (23)

○ Bevacizumab (AvastinⓇ), Crizotinib (XalkoriⓇ), Erlotinib (TarcevaⓇ), Gefitinib (IressaⓇ), Afatinib dimaleate (GilotrifⓇ), Ceritinib (LDK378/Zykadia™), Ramucirumab (CyramzaⓇ), Nivolumab (OpdivoⓇ), Pembrolizumab (KeytrudaⓇ), Osimertinib (Tagrisso™), Necitumumab (Portrazza™), Alectinib (AlecensaⓇ), Atezolizumab (TecentriqⓇ), Brigatinib (Alunbrig™), Trametinib (MekinistⓇ), Dabrafenib (TafinlarⓇ), Durvalumab (Imfinzi™), Dacomitinib (VizimproⓇ), Lorlatinib (LorbrenaⓇ), Entrectinib (Rozlytrek™), Capmatinib hydrochloride (Tabrecta™), Ipilimumab (YervoyⓇ), Selpercatinib (Retevmo™)

⑸ Skin (15)

○ Vismodegib (ErivedgeⓇ), Sonidegib (OdomzoⓇ), Ipilimumab (YervoyⓇ), Vemurafenib (ZelborafⓇ), Trametinib (MekinistⓇ), Dabrafenib (TafinlarⓇ), Pembrolizumab (KeytrudaⓇ), Nivolumab (OpdivoⓇ), Cobimetinib (Cotellic™), Alitretinoin (PanretinⓇ), Avelumab (BavencioⓇ), Encorafenib (Braftovi™), Binimetinib (MektoviⓇ), Cemiplimab-rwlc (LibtayoⓇ), Atezolizumab (TecentriqⓇ)

⑹ Kidney (13)

○ Bevacizumab (AvastinⓇ), Sorafenib (NexavarⓇ), Sunitinib (SutentⓇ), Pazopanib (VotrientⓇ), Temsirolimus (ToriselⓇ), Everolimus (AfinitorⓇ), Axitinib (InlytaⓇ), Nivolumab (OpdivoⓇ), Cabozantinib (Cabometyx™), Lenvatinib mesylate (LenvimaⓇ), Ipilimumab (YervoyⓇ), Pembrolizumab (KeytrudaⓇ), Avelumab (BavencioⓇ)

⑺ Liver (11)

○ Sorafenib (NexavarⓇ), Regorafenib (StivargaⓇ), Nivolumab (OpdivoⓇ), Lenvatinib mesylate (LenvimaⓇ), Pembrolizumab (KeytrudaⓇ), Cabozantinib (Cabometyx™), Ramucirumab (CyramzaⓇ), Ipilimumab (YervoyⓇ), Pemigatinib (Pemazyre™), Atezolizumab (TecentriqⓇ), Bevacizumab (AvastinⓇ)

⑻ Colorectal (10)

○ Cetuximab (ErbituxⓇ), Panitumumab (VectibixⓇ), Bevacizumab (AvastinⓇ), Ziv-aflibercept (ZaltrapⓇ), Regorafenib (StivargaⓇ), Ramucirumab (CyramzaⓇ), Nivolumab (OpdivoⓇ), Ipilimumab (YervoyⓇ), Encorafenib (Braftovi™), Pembrolizumab (KeytrudaⓇ)

⑼ Prostate (8)

○ Cabazitaxel (JevtanaⓇ), Enzalutamide (XtandiⓇ), Abiraterone acetate (ZytigaⓇ), Radium 223 dichloride (XofigoⓇ), Apalutamide (Erleada™), Darolutamide (NubeqaⓇ), Rucaparib camsylate (Rubraca™), Olaparib (Lynparza™)

⑽ Bladder (7)

○ Atezolizumab (TecentriqⓇ), Nivolumab (OpdivoⓇ), Durvalumab (Imfinzi™), Avelumab (BavencioⓇ), Pembrolizumab (KeytrudaⓇ), Erdafitinib (Balversa™), Enfortumab Vedotin-ejfv (Padcev™)

⑾ Thyroid (7)

○ Cabozantinib (CometriqⓇ), Vandetanib (CaprelsaⓇ), Sorafenib (NexavarⓇ), Lenvatinib mesylate (LenvimaⓇ), Trametinib (MekinistⓇ), Dabrafenib (TafinlarⓇ), Selpercatinib (Retevmo™)

⑿ Targeted therapy ＜ 5

○ gastric, cervical, ovarian, pancreatic, brain, head & neck, soft tissue sarcomam, MM, etc.

Input: 2022.04.24 14:19