Table 5.
Drugs targeting MC-derived tumors.
| Drug | Target | Mode of Action | References |
|---|---|---|---|
| Midostaurin Chemical name: N-[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo [1 2.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-N-methylbenzamide Brand name: Rydapt |
PKC alpha, VEGFR2, KIT | Antagonist and inhibitor | PubChem CID: 9829523 [103] |
| WT and/or mutant FLT3 tyrosine kinases | Apoptosis of target leukemia cells expressing target receptors and mast cells, Antiproliferative activity, Interacts with OATP | ||
| Imatinib Chemical name: 4-[(4-methylpiperazin-1-yl) methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide Brand name: Gleevec (USA) or Glivec (Europe/Australia) |
BCRP | Inhibitor | PubChem CID: 5291 [64] |
| MSCGFR KIT | Antagonist, multitarget | ||
| RET proto-oncogene | Inhibitor | ||
| HANGFR | Antagonist | ||
| PDGFRα | Antagonist | ||
| EDDCR 1 | Antagonist | ||
| KIT ABL1 | Inhibitor | ||
| Platelet-derived growth factor receptor beta | Antagonist | ||
| Dasatinib Chemical name: N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide |
KIT ABL1 | Multitarget-bind to both the active and inactive conformation of the ABL kinase domain | PubChem CID: 3062316 [59,83] |
| Proto-oncogene KIT Src | Multitarget | ||
| Ephrin type-A receptor 2 | Antagonist | ||
| KIT Lck | Multitarget | ||
| KIT | Inhibitor | ||
| MSCGFR Kit | Antagonist | ||
| PDGFRP | Antagonist | ||
| STAT5B | Inhibitor | ||
| Abelson KIT2 | Multitarget | ||
| KIT Fyn | Multitarget | ||
| Nilotinib Chemical name: 4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide |
KIT ABL1 | Inhibitor of BCR–ABL-binds to the inactive conformation of ABL | PubChem CID: 644241 [201] |
| MSCGFR Kit | Antagonist | ||
| Tranilast Chemical name: 2-[[(E)-3-(3,4-dimethoxyphenyl)prop-2-enoyl]amino]benzoic acid Brand name: Rizaben |
Hematopoietic prostaglandin D synthase | Inhibitor | PubChem CID: 5282230 [103,189] |
| MAP kinases (extracellularly regulated kinase 1 and 2 and JNK) | Calcium channel blocker, Antineoplastic agent, Aryl hydrocarbon receptor agonist and a hepatoprotective agent, Inhibit TGF-β production, interferon-gamma, IL-6, IL-10, and IL-17 by lymphoid cells | ||
| Gabexate Chemical name: 4-[[6-[(Aminoiminomethyl)amino]-1-oxohexyl]oxy]-benzoic acid ethyl ester mesylate Brand name: Gabexate mesylate (Japan), Foy (Taiwan), Reminaron (Japan) |
Serine protease Thrombin Trypsin Plasminogen Plasma kallikrein |
Inhibitor, Antithrombotic in vitro and in vivo, inhibits LPS-induced TNF-α production, Inhibiting NF-κB and AP-1 activation |
PubChem CID: 3447 [202] |
| Nafamostat mesylate Chemical name: (6-carbamimidoylnaphthalen-2-yl) 4-(diaminomethylideneamino)benzoate Brand name: Fusan |
Serine protease | Inhibits enzyme: thrombin, Xa, and XIIa), The kallikrein–kinin system, The complement system, Pancreatic proteases and activation of protease-activated receptors (PARs), Lipopolysaccharide-induced nitric oxide production, apoptosis, Interleukin (IL)-6 and IL-8. Antioxidant in TNF-α-induced ROS production | PubChem CID: 5311180 [203] |
| Prothrombin Coagulation factor X Coagulation factor XII Trypsin-1 Kallikrein-1 Intracellular adhesion molecule 1 |
Inhibitor | ||
| Masitinib mesylate Chemical name: N-(4-methyl-3-{[4-(pyridin-3-yl)-1,3-thiazol-2-yl]amino}phenyl)-4-[(4-methylpiperazin-1-yl)methyl]benzamide Brand name: Masivet, Kinavet |
Tyrosine-kinase PDGF and KIT | Inhibiting the stem cell factor that regulates mast cell tumor proliferation, Antiproliferative actions- targets the c-KIT pathway | PubChem CID: 25024769 [103] |
| Avapritinib Chemical name: (1S)-1-(4-fluorophenyl)-1-(2-{4-[6-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl}pyrimidin-5-yl)ethan-1-amine Brand name: Ayvakit |
MSCGFR KIT and PDGFR alpha |
Inhibitor Negatively modulates the action of cell transporters |
PubChem CID: 118023034 [204] |
| Obatoclax Chemical name: 2-[(2Z)-2-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-3-methoxy-2H-pyrrol-5-yl]-1H-indole |
Apoptosis regulator Bcl-2 | Leads to release of apoptosis-inducing cytochromec | PubChem CID: 11404337 [205] |
| Bcl-2 family of proteins | Displaces BH3 domains by activation of a pocket of the BcL-2 family member | ||
| Gemcitabine Chemical name: 4-amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one Brand name: Gemzar, Infugem |
Block DNA Replication DNA during the “S” phase (or DNA synthesis phase of the cell cycle), stopping normal development and division | Cross-linking/Alkylation | PubChem CID: 60750 [206] |
| Ribonucleoside-diphosphate reductase large subunit | Blocks an enzyme which converts the cytosine nucleotide into the deoxy derivative | ||
| Thymidylate synthase | Blocks the incorporation of the thymidine nucleotide | ||
| UMP-CMP kinase | Inhibitor | ||
| Orantinib Chemical name: 3-(2,4-dimethyl-5-{[(3Z)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]methyl}-1H-pyrrol-3-yl)propanoic acid |
KIT autophosphorylation VEGFR2 PDGFR FGFR angiogenesis proliferation |
Inhibitor | PubChem CID: 5329099 [207] |
| Cromolyn Chemical name: 5-{3-[(2-carboxy-4-oxo-4H-chromen-5-yl)oxy]-2-hydroxypropoxy}-4-oxo-4H-chromene-2-carboxylic acid Brand name: Spinhaler, nebulizer solution, metered-dose inhaler, NasalCrom, Nasal Allergy Control, Nasalcrom Child |
Protein S100-P | Antagonist | PubChem CID: 2882 [99,200] |
| Calcium sensor Capsaicin receptor |
Ion channel blockade Blockade |
||
| Cellular calcium signaling | Blockade of signaling of heat shock protein or G-protein | ||
| Stabilizing mast cells | Prevents the subsequent release of mediators; Precise mechanism/clinical activity not delineated |