Drug Library
Recommended article: 【Chemistry】 Chapter 16-1. Pharmacology, 【Bioinformatics】 Bioinformatics Index
1. Overview
6. Cell therapy
1. Overview
⑴ Recent Drug Trends: Increased drug size, increased fat solubility (clogP)This is contrary to Ripinsky’s rule of 5.
⑵ For other information, see https://www.scinapse.io/ and https://typeset.io/, which curated billions of papers.
2. Small Molecule Drugs
○ Overview
① -nib suffix: In the smallmoleculeinhibitor, abbreviate “inhibit” to -nib
○ alexidine: Targeting DDR2
○ AMD3100: CXCR4 inhibitor
○ anifrolumab
① IFNAR1 antagonist
② FDA approval for SLE (Systemic Lupus erythematosus) treatment in 2021
○ AVL-292: BTK inhibitor
○ AZD7762: CHEK1/2 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
○ ciliobrevin D: inhibitor of degranulation of NK cells
○ cinnamaldehyde: cinnamon flavoring
○ cisplatin: FAP inhibitor
○ CNX-774: BTK 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
○ decitabine : DNMT inhibitor
○ deoxycholic acid: Component of subsequent fat removal injection. trademark name is Kybella
○ diethylstilbestrol (DES)
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
○ diazinon: insect repellent
○ dopa: A treatment for Parkinson’s disease, is effective in its L-form only.
○ doxycyclin: be used as an anticancer drug
○ enediyne: anti-cancer drug
○ esomeprazole: proton pump inhibitor, digestive medicine
○ finerenone
① NR3C2 antagonist
② FDA approval for CKD (chronic kidney disease) treatment in 2021
○ galunisertib (LY21577299) : TGF-βR1 inhibitor
○ gemcitabine
① first line drug of pancreatic cancer
② pyrimidine antimetabolite
○ 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.
○ 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
○ (-)-iridomyrmecin: compounds released when ants try to protect themselves from predators
○ ispinesib: Specifically inhibits Kinesin spindle protein (KSP)
○ JQ1: BRD2,BRD3,BRD4,BRDT inhibitor
○ lobeglitazone (Lobe)
① antiatherogenic drug
② promotes cholesterol efflux (through PPARγ activation & LXRα, ABCA1, and ABCG1 dependent pathways)
○ losartan: angiotensin inhibitor
○ loxonin: Painkillers
○ (S)-methamphetamine:illegal // (R)-methamphetamine:legal
○ nandrolone: anabolic steroids illegally used by athletes to strengthen their muscles
○ NEM(N-ethylmaleimide): chemical that binds to myosin and inhibits its function
○ niclosamide: anthelminthic drug
○ palbociclib
○ An FDA-approved treatment for breast cancer.
○ It selectively inhibits cyclin-dependent kinases CDK4 and CDK6.
○ panobinostat: pan‐HDAC inhibitor
○ PD173074: specific VEGFR inhibitor
○ phalloidin: Targeting actin filament
○ RGFP966: Targeting GATA2
○ ricin: ribosome-inactivating protein created by Ricinus communis
○ S1 nuclease: Hydrolyze all of the nucleic acid endotransferase, single-stranded DNA, or RNA isolated from Aspergillus aurizae
○ sotorasib
FDA approval for KRASG12C non-small-cell lung canceller
○ talabostat: FAP inhibitor
○ tazemetostat: EZH2 inhibitor
○ tepoxalin: It specifically kills cells with high ABCB1 expression.
○ tirofiban: Glycoprotein IIb/IIIa receptor inhibitor.
○ toxane: microtubule toxin
○ transgelin: smooth muscle marker
○ trifluralin B: non-selective herbicide.
○ vanadium: It specifically kills cells with high SLC26A2 expression.
○ vanillin: Vanilla flavoring.
○ vismodegib: SHH inhibitor
○ vorinostat: α histone deacetylase inhibitor.
○ wortmannin: PI3K inhibitor
○ VS-4718: FAK inhibitor
○ 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
○ 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
○ 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℃)
○ Gardine tablet
① lanitidine hydrochlorideH2 blockers and gastric acid secretion inhibitors
② Prevention and treatment for gastric ulcer, duodenal ulcer, gastroesophageal reflux disease
○ 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
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 Types of Antibody Drugs: be labeled as “antigen:antibody”
○ CAIX: cG250
○ CD20: rituximab, ibritumomab tiuxetan, tositumomab
○ CD3: CD8 T cell activator
○ CD3/CD28: CD4 T cell activator
○ CD30: brentuximab vedotin
○ CD33: gemtuzumab ozogamicin
○ CD4/8: T cell depletion
○ CD52: alemtuzumab
○ CEA: labetuzumab
○ EGFR: cetuximab, panitumumab, nimotuzumab, 806
○ EpCAM: IGN101, adecatumumab
○ EPHA3: KB004, IIIA4
○ ERBB2: trastuzumab, pertuzumab
○ ERBB3: MM-121
○ FAP: sibrotuzumab, F19
○ folate binding protein: MOv18, MORAb-003 (farletuzumab)
○ ganglioside (e.g., GD2, GD3, GM2): 3F8, ch14.18, KW-2871
○ gpA33: huA33
○ IGF1R: AVE1642, IMC-A12, MK-0646, R1507, CP751871
○ integrin α5β1: volociximab
○ integrin αVβ3: etaracizumab
○ Leγ: hu3S193, IgN311
○ MET: AMG102, METMAB, SCH900105
○ mucin: pemtumomab, oregovomab
○ PSMA: J591
○ RANKL: denosumab
○ TAG-72: CC49 (minretumomab)
○ tenascin: 81C6
○ trastuzumab
○ trastuzumabThis glioblastoma is actually the only drug.
○ 98% of small molecule drug is suppressed by close connection of brain capillaries.
○ tocilizumab: anti-IL-6R humanized monoclonal antibody
○ TRAILR1: mapatumumab (HGS-ETR1)
○ TRAILR2: HGS-ETR2, CS-1008
○ VEGF: ranibizumab, aflibercept, bevacizumab
○ VEGFR: sunitinib, pazopanib, axitinib, IM2C6, CDP791
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 1st. Extract T cell from patient’s blood
② 2nd. Inject the inactive virus into the T cell to express an engineered receptor.
③ 3rd. GROWTH TO MILLIONS OF CELL
④ 4th. 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): 2017
○ Axicabtagene ciloleucel (Yescarta): 2017
○ Brexucabtagene autoleucel (Tecartus): 2020
○ Lisocabtagene maraleucel (Breyanzi): 2021
○ Iidecabtagene vicleucel (Abecma): 2021
⑶ Type 2. Sipuleucel-T
① Examples of Cancer vacine for treatment
② 1st. Extract antigen-presenting cells (APCs) from patients
③ 2nd. Exposurend of antigen to antigen-presenting cells in vitro
④ 3rd. 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)
Input: 2022.04.24 14:19