The World Health Organization's ATC classification organizes medical drugs based on therapeutic properties, chemical composition, and anatomy. It helps make essential medicines readily available globally and is widely used in the pharmaceutical industry.
Aflibercept, also known as VEGF TRAP in the scientific literature, is a recombinant fusion protein consisting of VEGF-binding portions from the extracellular domains of human VEGF receptors 1 and 2 fused to the Fc portion of the human IgG1. Aflibercept blocks the activation of VEGF receptors and the proliferation of endothelial cells, thereby inhibiting the growth of new vessels that supply tumours with oxygen and nutrients.
Alitretinoin is a naturally-occurring endogenous hormone related to vitamin A, binds to and activates all known intracellular retinoid receptor subtypes (RAR, RAR, RAR, RXR, RXR, RXR). The efficacy of alitretinoin in treating KS lesions may be related to the demonstrated ability of alitretinoin to inhibit the in vitro growth of KS cells.
Altretamine is an antineoplastic agent. It is indicated for use as a single agent in the palliative treatment of patients with persistent or recurrent ovarian cancer following first-line therapy with cisplatin and/or alkylating agent-based combination. It is not considered a first-line treatment, but it can be useful as salvage therapy.
5-Aminolevulinic acid (5-ALA) is a natural biochemical precursor of heme that is metabolised in a series of enzymatic reactions to fluorescent porphyrins, particularly PPIX. 5-ALA synthesis is regulated by an intracellular pool of free heme via a negative feedback mechanism. Administration of excess exogenous 5-ALA avoids the negative feedback control, and accumulation of PPIX occurs in target tissue. In the presence of visible light, fluorescence of PPIX (photodynamic effect) in certain target tissues can be used for photodynamic diagnosis.
Amsidine is a sterile antitumour chemotherapeutic agent for intravenous infusion. Although not completely clarified, the mode of action of amsacrine is related to its property of binding the DNA through intercalation and external (electrostatic) forces.
Anagrelide is an inhibitor of cyclic AMP phosphodiesterase III and suppress expression of transcription factors including GATA-1 and FOG-1 required for megakaryocytopoiesis, ultimately leading to reduced platelet production.
Arsenic trioxide causes morphological changes and deoxyribonucleic acid (DNA) fragmentation characteristic of apoptosis in NB4 human promyelocytic leukaemia cells in vitro. Arsenic trioxide also causes damage or degradation of the fusion protein PML/RAR alpha.
Asparaginase hydrolyses asparagine to aspartic acid and ammonia. In contrast to normal cells, lymphoblastic tumour cells have a very limited capacity for synthesising asparagine because of a significantly reduced expression of asparagine synthetase. Therefore, they require asparagine which diffuses from the extracellular environment. As a result of asparaginase-induced asparagine depletion in serum, protein synthesis in lymphoblastic tumour cells is disturbed while sparing most normal cells.
Axicabtagene ciloleucel, an engineered autologous T-cell immunotherapy product, binds to CD19 expressing cancer cells and normal B cells. Following anti-CD19 CAR T-cell engagement with CD19 expressing target cells, a sequence of events leads to apoptosis and necrosis of CD19-expressing target cells. Αxicabtagene ciloleucel is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL), after two or more lines of systemic therapy.
Belinostat is a histone deacetylase (HDAC) inhibitor. Belinostat shows preferential cytotoxicity towards tumor cells compared to normal cells. It is indicated for the treatment of adult patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).
Bexarotene is a synthetic compound that exerts its biological action through selective binding and activation of the three RXRs: α, β, and γ. Once activated, these receptors function as transcription factors that regulate processes such as cellular differentiation and proliferation, apoptosis, and insulin sensitisation. The exact mechanism of action of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL) is unknown.
Bortezomib is a proteasome inhibitor. It is specifically designed to inhibit the chymotrypsin-like activity of the 26S proteasome in mammalian cells. Inhibition of the 26S proteasome prevents this targeted proteolysis and affects multiple signalling cascades within the cell, ultimately resulting in cancer cell death.
Carboplatin interferes with DNA intrastrand and interstrand crosslinks in cells exposed to the drug. DNA reactivity has been correlated with cytotoxicity.
Carfilzomib is a tetrapeptide epoxyketone proteasome inhibitor that selectively and irreversibly binds to the N-terminal threonine containing active sites of the 20S proteasome, the proteolytic core particle within the 26S proteasome, and displays little to no activity against other protease classes. Carfilzomib had antiproliferative and proapoptotic activities in preclinical models in haematologic tumours.
Celecoxib is an oral, selective, cyclooxygenase-2 (COX-2) inhibitor within the clinical dose range (200-400 mg daily). No statistically significant inhibition of COX-1 (assessed as ex vivo inhibition of thromboxane B2 [TxB2] formation) was observed in this dose range in healthy volunteers.
Ciltacabtagene autoleucel is a BCMA-directed, genetically modified autologous T cell immunotherapy, which involves reprogramming a patient’s own T cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that express BCMA. BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells.
Cisplatin is an anorganic substance containing a heavy metal [cis-diamminedichloroplatinum(II)]. This substance inhibits the DNA synthesis by realising transverse connections within and between the DNA strings. The protein and RNA synthesis is inhibited to a lesser extent.
Denileukin diftitox is a recombinant DNA-derived cytotoxic protein composed of the amino acid sequences for diphtheria toxin fragments A and B (Met1 –Thr387)-His and the sequences for human interleukin-2 (IL-2; Ala1 –Thr133).
Enasidenib is a small molecule inhibitor of the isocitrate dehydrogenase 2 (IDH2) enzyme. Enasidenib targets the mutant IDH2 variants R140Q, R172S, and R172K at approximately 40-fold lower concentrations than the wild-type enzyme in vitro. Inhibition of the mutant IDH2 enzyme by enasidenib led to decreased 2-hydroxyglutarate (2-HG) levels and induced myeloid differentiation in vitro and in vivo in mouse xenograft models of IDH2 mutated AML. In blood samples from patients with AML with mutated IDH2, enasidenib decreased 2-HG levels, reduced blast counts and increased percentages of mature myeloid cells.
Eribulin is a microtubule dynamics inhibitor belonging to the halichondrin class of antineoplastic agents. It is a structurally simplified synthetic analogue of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai.
Estramustine is a chemical compound of oestradiol and nitrogen mustard. It is effective in the treatment of advanced prostatic carcinoma. Estramustine has a dual mode of action. The intact molecule acts as an anti-miotic agent; after hydrolysis of the carbamate ester, the metabolites act to bridge the released oestrogens and exert an anti-gonadotrophic effect.
Glasdegib is an inhibitor of the Hedgehog (Hh) signal transduction pathway that binds to Smoothened (SMO), a transmembrane protein, leading to decreased Glioma-Associated Oncogene (GLI) transcription factor activity and downstream pathway signalling. Hh pathway signalling is required for maintaining a leukaemic stem cell (LSC) population thus, glasdegib binding to and inhibiting SMO reduces GLI1 levels in AML cells and the leukaemic initiating potential of AML cells.
One of the mechanisms by which hydroxycarbamide acts is the elevation of foetal haemoglobin (HbF) concentrations in sickle cell patients. In addition hydroxycarbamide causes an immediate inhibition of DNA synthesis by acting as a ribonucleotide reductase inhibitor, without interfering with the synthesis of ribonucleic acid or protein.
Idecabtagene vicleucel is a chimeric antigen receptor (CAR)-positive T cell therapy targeting B-cell maturation antigen (BCMA), which is expressed on the surface of normal and malignant plasma cells. The CAR construct includes an anti-BCMA scFv-targeting domain for antigen specificity, a transmembrane domain, a CD3-zeta T cell activation domain, and a 4-1BB costimulatory domain. Antigen-specific activation of idecabtagene vicleucel results in CAR-positive T cell proliferation, cytokine secretion and subsequent cytolytic killing of BCMA-expressing cells.
Ivosidenib is a small molecule inhibitor that targets the mutant isocitrate dehydrogenase 1 (IDH1) enzyme. Susceptible IDH1 mutations are defined as those leading to increased levels of 2-hydroxyglutarate (2-HG) in the leukemia cells and where efficacy is predicted by 1) clinically meaningful remissions with the recommended dose of ivosidenib and/or 2) inhibition of mutant IDH1 enzymatic activity at concentrations of ivosidenib sustainable at the recommended dosage according to validated methods. The most common of such mutations are R132H and R132C substitutions.
Ixazomib is an oral, highly selective and reversible proteasome inhibitor. Ixazomib preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome. Ixazomib induced apoptosis of several tumour cell types in vitro. In vivo, ixazomib demonstrated antitumour activity in various tumour xenograft models, including models of multiple myeloma.
Methyl aminolevulinate is a prodrug that is metabolized to protoporphyrin. After topical application of methyl aminolevulinate, porphyrins accumulate intracellularly in the treated skin lesions. The intracellular porphyrins (including PpIX) are photoactive, fluorescing compounds and, upon light activation in the presence of oxygen, singlet oxygen is formed which causes damage to cellular compartments, in particular the mitochondria. Light activation of accumulated porphyrins leads to a photochemical reaction and thereby phototoxicity to the light-exposed target cells.
Mitotane is an adrenal cytotoxic active substance, although it can apparently also cause adrenal inhibition without cellular destruction. Available data suggest that mitotane modifies the peripheral metabolism of steroids and that it also directly suppresses the adrenal cortex. The administration of mitotane alters the extra-adrenal metabolism of cortisol in humans, leading to a reduction in measurable 17-hydroxy corticosteroids, even though plasma levels of corticosteroids do not fall.
Niraparib is an inhibitor of poly(ADP-ribose) polymerase (PARP) enzymes, PARP-1 and PARP-2, which play a role in DNA repair.
Olaparib is a potent inhibitor of human poly (ADP-ribose) polymerase enzymes (PARP-1, PARP-2 and PARP-3), and has been shown to inhibit the growth of selected tumour cell lines in vitro and tumour growth in vivo either as a standalone treatment or in combination with established chemotherapies.
Omacetaxine mepesuccinate is a cephalotaxine ester. The mechanism of action of omacetaxine mepesuccinate has not been fully elucidated but includes inhibition of protein synthesis and is independent of direct Bcr-Abl binding. It is used for the treatment of patients with chronic or accelerated phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKI).
Oxaliplatin is an antineoplastic active substance belonging to a new class of platinum-based compounds in which the platinum atom is complexed with 1,2-diaminocyclohexane (“DACH”) and an oxalate group.
Padeliporfin is retained within the vascular system. When activated with 753 nm wavelength laser light, padeliporfin triggers a cascade of pathophysiological events resulting in focal necrosis within a few days.
Panobinostat is a histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDACs at nanomolar concentrations. HDACs catalyse the removal of acetyl groups from the lysine residues of histones and some non-histone proteins. Inhibition of HDAC activity results in increased acetylation of histone proteins, an epigenetic alteration that results in a relaxing of chromatin, leading to transcriptional activation.
Pegaspargase is a covalent conjugate of Escherichia coli-derived L-asparaginase with monomethoxypolyethylene glycol. The mechanism of action of L-asparaginase is the enzymatic cleavage of the amino acid L-asparagine into aspartic acid and ammonia. Depletion of L-asparagine in blood results in inhibition of protein-synthesis, DNA-synthesis and RNA-synthesis, especially in leukaemic blasts which are not able to synthesise L-asparagine, thus undergoing apoptosis.
Pentostatin is a potent transition state inhibitor of the enzyme adenosine deaminase. The greatest activity of ADA is found in cells of the lymphoid system with T-cells having higher activity than B-cells and T-cell malignancies higher ADA activity than B-cell malignancies. Pentostatin has been shown to have activity against a variety of lymphoid malignancies, but is most active against indolent cancers with lower ADA concentration, such as hairy cell leukaemia.
Porfimer is a mixture of porphyrin units, which are linked together in chains of two to eight units The cytotoxic actions of porfimer are light- and oxygen-dependent. Photodynamic therapy with porfimer is a 2-stage process. Cellular damage caused by porfimer PDT is a consequence of the propagation of free radical reactions.
Procarbazine, a methylhydrazine derivative, is a cytostatic agent with weak MAO inhibitor properties. Its exact mode of action on tumour cells is unknown.
Rucaparib is an inhibitor of poly(ADP-ribose) polymerase (PARP) enzymes, including PARP-1, PARP-2, and PARP-3, which play a role in DNA repair. In vitro studies have shown that rucaparibinduced cytotoxicity involves inhibition of PARP enzymatic activity and the trapping of PARP-DNA complexes resulting in increased DNA damage, apoptosis, and cell death.
Satraplatin is a cytotoxic agent. The primary cytotoxic mechanism of satraplatin is similar to that of other platinum compounds including cisplatin, carboplatin and oxaliplatin, and is based on the formation of DNA adducts. Platinum-DNA adducts, which are formed following uptake of the drug into the nucleus of the cell, activate several cellular processes that mediate the cytotoxicity of these drugs. These processes include the signalling of DNA damage, cell cycle checkpoints and arrest, DNA repair and cell death.
Selinexor is a nuclear export inhibitor. In nonclinical studies, selinexor reversibly inhibits nuclear export of tumor suppressor proteins (TSPs), growth regulators, and mRNAs of oncogenic proteins by blocking exportin 1 (XPO1).
Sonidegib is an orally bioavailable inhibitor of the Hh signalling pathway. It binds to Smoothened (Smo), a G protein-coupled receptor-like molecule that positively regulates the Hh pathway. Aberrant Hh signalling has been linked to the pathogenesis of several types of cancer, including basal cell carcinoma (BCC). Sonidegib binding to Smo will inhibit Hh signalling and consequently block signal transduction.
Sotorasib is a selective KRAS G12C (Kirsten rat sarcoma viral oncogene homolog) inhibitor, which covalently and irreversibly binds to the unique cysteine of KRAS G12C. Inactivation of KRAS G12C by sotorasib blocks tumour cell signalling and survival, inhibits cell growth, and promotes apoptosis selectively in tumours harbouring KRAS G12C, an oncogenic driver of tumourigenesis.
Tagraxofusp is a CD123-directed cytotoxin composed of recombinant human interleukin-3 (IL-3) and truncated diphtheria toxin (DT) fusion protein that inhibits protein synthesis and causes cell death in CD123-expressing cells. It is used for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN).
Talazoparib is an inhibitor of PARP enzymes, PARP1, and PARP2. PARP enzymes are involved in cellular DNA damage response signalling pathways such as DNA repair, gene transcription, and cell death. PARP inhibitors (PARPi) exert cytotoxic effects on cancer cells by 2 mechanisms, inhibition of PARP catalytic activity and by PARP trapping, whereby PARP protein bound to a PARPi does not readily dissociate from a DNA lesion, thus preventing DNA repair, replication, and transcription, thereby resulting in apoptosis and/or cell death.
Talimogene laherparepvec is an oncolytic immunotherapy that is derived from HSV-1. Talimogene laherparepvec has been modified to replicate within tumours and to produce the immune stimulatory protein human GM-CSF. Talimogene laherparepvec causes the death of tumour cells and the release of tumour-derived antigens.
Tebentafusp is a bispecific fusion protein, comprised of a T cell receptor (TCR; targeting domain) fused to an antibody fragment targeting CD3 (cluster of differentiation 3; effector domain). The TCR end binds with high affinity to a gp100 peptide presented by human leukocyte antigen – A*02:01 (HLA-A*02:01) on the cell surface of uveal melanoma tumour cells, and the effector domain binds to the CD3 receptor on the polyclonal T cell.
Tisagenlecleucel is an autologous, immunocellular cancer therapy which involves reprogramming a patient’s own T cells with a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19 expressing cells.
Tretinoin decreases cohesiveness of follicular epithelial cells resulting in decreased microcomedone formation. Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells, causing extrusion of the comedones.
Venetoclax is a potent, selective inhibitor of B-cell lymphoma (BCL)-2, an anti-apoptotic protein. Overexpression of BCL-2 has been demonstrated in CLL cells where it mediates tumour cell survival and has been associated with resistance to chemotherapeutics. Venetoclax binds directly to the BH3-binding groove of BCL-2, displacing BH3 motif-containing pro-apoptotic proteins like BIM, to initiate mitochondrial outer membrane permeabilization (MOMP), caspase activation, and programmed cell death.
Vismodegib is an orally available small-molecule inhibitor of the Hedgehog pathway. Hedgehog pathway signalling through the Smoothened transmembrane protein (SMO) leads to the activation and nuclear localisation of Glioma-Associated Oncogene (GLI) transcription factors and induction of Hedgehog target genes. Vismodegib binds to and inhibits the SMO protein thereby blocking Hedgehog signal transduction.
Vorinostat inhibits the enzymatic activity of histone deacetylases HDAC1, HDAC2 and HDAC3 (Class I) and HDAC6 (Class II) at nanomolar concentrations. Inhibition of HDAC activity allows for the accumulation of acetyl groups on the histone lysine residues resulting in an open chromatin structure and transcriptional activation. In vitro, vorinostat causes the accumulation of acetylated histones and induces cell cycle arrest and/or apoptosis of some transformed cells.