Raltitrexed is an antimetabolite drug used in chemotherapy, acting by inhibiting thymidylate synthase.
Anticancer agent 82 is a FiVe1 derivative, an orally active and selective anticancer agent. FiVe1 binds type III intermediate filament protein vimentin (VIM), to induce hyperphosphorylation of Ser56, resulting selective disruption of mitosis and multinucleation in transformed VIM-expressing mesenchymal cancer cells. Anticancer agent 82 shows better oral bioavailability and pharmacokinetic profiles than FiVe1[1].
Avdoralimab (IPH 5401) is a fully human IgGκ monoclonal antibody that targets the complement C5a receptor 1 (C5aR1) that prevents its binding to C5a. Avdoralimab can be used for complement-driven inflammatory diseases and solid tumours research[1].
Quarfloxin (CX 3543), a fluoroquinolone derivative with antineoplastic activity, targets and inhibits RNA pol I activity, with IC50 values in the nanomolar range in neuroblastoma cells. Quarfloxin disrupts the interaction between the nucleolin protein and a G-quadruplex DNA structure in the ribosomal DNA (rDNA) template[1].
[D-Arg1,D-Phe5,D-Trp7,9,Leu11]-Substance P, a Substance P derivative, is a biased agonist toward neuropeptide and chemokine receptors. [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-Substance P activates G12. [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-Substance P binds to IL-8 and GRP receptors. [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-Substance P inhibits ERK-2 activation, activates JNK activity. [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-Substance P stimulates an increase in neutrophil migration and Ca2+ mobilization. [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-Substance P is also a bombesin antagonist, and inhibits the growth of small cell lung cancer[1][2][3]
Mogroside I E1, a triterpenoid glycoside isolated from the extracts of Luo Han Guo, is a nonsugar sweetener. Mogrosides are sweeter than sucrose. Mogrosides exhibit antioxidant, antidiabetic and anticancer activities[1].
Chrysotobibenzyl can be isolated from stem of Dendrobium pulchellum. Chrysotobibenzyl inhibits lung cancer cell (H460 and H292) migration, invasion, filopodia formation via Cav-1, integrins β1, β3, and αν, and EMT suppressions. Chrysotobibenzyl also sensitizes lung cancer cell death mediated by Cisplatin (HY-17394)[1].
Epothilone D is a potent microtubule stabilizer.
CDK2/4/6-IN-1(example 29) is a CDK2/4/6 inhibitor with IC50 values of 2.5, 23.7 and 44.3 nM for CDK2, CDK4 and CDK6, respectively. CDK2/4/6-IN-1 can be used in cancer research[1].
Ambazone is an orally active membrane active antitumor agent. Ambazone also shows antibacterial and weak antiviral activities[1].
Ganoderic acid LM2 is a natural terpenoid isolated from the Fungus Ganoderma lucidum. Ganoderic acid LM2 possesses potential anti-tumor activity[1].
Methylproamine is a DNA-binding radioprotector which, on the basis of published pulse radiolysis studies, acts by repair of transient radiation-induced oxidative species on DNA.IC50 Value: N/ATarget: DNA-binding radioprotectorin vitro: The extent of radioprotection at the clonogenic survival endpoint increased with methylproamine concentration up to a maximum dose modification factor (DMF) of 2.0 at 10 μM. At least 0.1 fmole/nucleus of methylproamine is required to achieve a substantial level of radioprotection (DMF of 1.3) with maximum protection (DMF of 2.0) achieved at 0.23 fmole/nucleus. The γH2AX focus yield per cell nucleus 45 min after irradiation decreased with drug concentration with a DMF of 2.5 at 10 μM [1]. Methylproamine-treated cells had fewer γH2AX foci after IR compared to untreated cells. Also, the presence ofmethylproamine decreased the amount of lower molecular weight DNA entering the gel as shown by the pulsed field gel electrophoresis assay [2]. Experiments with V79 cells have shown that methylproamine is approximately 100-fold more potent than the classical aminothiol radioprotector WR1065. The crystal structures of methylproamine and proamine complexes with the dodecamer d(CGCGAATTCGCG)(2) confirm that the new analogues also are minor groove binders [3].in vivo: N/AClinical trial: N/A
AKR1C3-IN-6 (Compound 1) is a potent, selective AKR1C3 inhibitor with IC50 values of 0.31 μM and 73.23 μM against AKR1C3 and AKR1C2, respectively. AKR1C3-IN-6 shows antitumor activity[1].
CBP/p300-IN-19 is a potent p300/CBP HAT inhibitor with IC50s of 1.4, 2.2, >100, >100 µM for p300-HAT, CBP-HAT, PCAF, Myst3, respectively. CBP/p300-IN-19 shows antitumor activity[1].
Baohuoside I, a flavonoid isolated from Epimedium koreanum Nakai, acts as an inhibitor of CXCR4, downregulates CXCR4 expression, induces apoptosis and shows anti-tumor activity.
Paris saponin VII (Chonglou Saponin VII) is a steroidal saponin isolated from the roots and rhizomes of Trillium tschonoskii Maxim. Paris saponin VII-induced apoptosis in K562/ADR cells is associated with Akt/MAPK and the inhibition of P-gp. Paris saponin VII attenuates mitochondrial membrane potential, increases the expression of apoptosis-related proteins, such as Bax and cytochrome c, and decreases the protein expression levels of Bcl-2, caspase-9, caspase-3, PARP-1, and p-Akt. Paris saponin VII induces a robust autophagy in K562/ADR cells and provides a biochemical basis in the treatment of leukemia[1].
Cycloheximide (Naramycin A) is an eukaryote protein synthesis inhibitor, with IC50s of 532.5 nM and 2880 nM for protein synthesis and RNA synthesis in vivo, respectively.
ar-Turmerone ((+)-ar-Turmerone) is a major bioactive compound of the herb Curcuma longa with anti-tumorigenesis and anti-inflammatory activities[1][2][3]. ar-turmerone ((+)-ar-Turmerone) activates apoptotic protein in human lymphoma U937 cells[3]. ar-Turmerone ((+)-ar-Turmerone) exerts positive modulation on murine DCs, induces NSC proliferation and constitutes a promising therapeutic agent for various neurologic disorders[4][5].
Damulin B is a dammarane-type saponin found in Gynostemma pentaphyllum.Damulin B can induce cell apoptosis and has anti-cancer activities in vitro[1][2].
L-threo-PPMP is a GlcT (UDP-Glc: Ceramide β1,1glucosyltransferase) inhibitor. L-threo-PPMP inhibits glycosphingolipid biosynthesis and induces apoptosis. L-threo-PPMP has anti-cancer activity[1].
o-Vanillin (2-Vanillin) is a nature product, could be extracted from Vanilla planifolia, Pinus koraiensis fruit. o-Vanillin is a potent antifungal agent. o-Vanillin inhibits the growth of mycelia by disrupting the integrity of cell walls and cell membranes. o-Vanillin inhibits Doxorubicin (HY-15142A)- and 4-hydroperoxycyclophosphamide-induced NF-κB activation[1][2].
Selenocystine is a broad-spectrum anti-cancer agent. Selenocystine induces DNA damage in HepG2 cells, particularly in the form of DNA double strand breaks (DSBs). Selenocystine exhibits great promise as a therapeutic or adjuvant agent targeting DNA repair for cancer treatment[1].
Selicrelumab is an agonist CD40 antibody, induces changes in the tumor microenvironment. Selicrelumab can be used for the research of pancreatic cance and neoadjuvant study[1].
1,4-O-Diferuloylsecoisolariciresinol (compound 7) is a nature product that could be isolated from Hypericum nagasawae. 1,4-O-Diferuloylsecoisolariciresinol can be used in research of cancer[1].
N6-Bz-5’-O-DMTr-2’-O-hexadecanyl adenosine is a purine nucleoside analog. Purine nucleoside analogs have broad antitumor activity targeting indolent lymphoid malignancies. Anticancer mechanisms in this process rely on inhibition of DNA synthesis, induction of apoptosis, etc[1].
BCR-ABL-IN-5 (compound II) is a Bcr-Abl kinase (Breakpoint cluster region-Abelson) inhibitor. BCR-ABL-IN-5 inhibits Bcr-AblWT and Bcr-AblT3151 with the IC50 value of 0.014 μM and 0.45 μM, respectively. BCR-ABL-IN-5 has some anti-proliferative activity against leukemic cells[1].
Ursolic acid(Bungeolic acid) is a natural pentacyclic triterpenoid carboxylic acid, exerts anti-tumor effects and is an effective compound for cancer prevention and therapy. IC50 value:Target:in vitro: UA induced phosphorylation of AMP-activated protein kinase alpha (AMPKα) and suppressed the protein expression of DNA methyltransferase 1 (DNMT1) in the dose-dependent manner [1]. The combination of ursolic acid (0.5 μM) and leucine (10 μM) proved to be the most effective in promoting myogenic differentiation. The combination of ursolic acid and leucine significantly increased CK activity than treatment with either agent alone. The level of myosin heavy chain, a myogenic differentiation marker protein, was also enhanced by the combination of ursolic acid and leucine [2]. Ursolic acid efficiently induced apoptosis, possibly via the downregulation of B-cell lymphoma 2 (Bcl-2), the upregulation of Bcl-2-associated X protein and the proteolytic activation of caspase-3. Furthermore, the activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase was increased by the administration of ursolic acid. In addition, ursolic acid significantly suppressed the invasive phenotype of the SNU-484 cells and significantly decreased the expression of matrix metalloproteinase (MMP)-2 [3]. ursolic acid (UA) potently induces the apoptosis of gastric cancer SGC-7901 cells. Further mechanistic studies revealed that the ROCK1/PTEN signaling pathway plays a critical role in UA-mediated mitochondrial translocation of cofilin-1 and apoptosis [4].in vivo: UA treatment markedly improved the survival of septic rats, and attenuated CLP-induced lung injury, including reduction of lung wet/dry weight ratio, infiltration of leukocytes and proteins, myeloperoxidase activity, and malondialdehyde content. In addition, UA significantly decreased the serum levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β, inhibited the expression of inducible nitric oxide synthase and cyclooxygenase-2 in the lung, which are involved in the productions of nitric oxide and prostaglandin E2 [5].
2-mercaptoethane sulfonate (Mesna), is a synthetic small molecule, widely used as a systemic protective agent against chemotherapy toxicity, but is primarily used to reduce hemorrhagic cystitis induced by cyclophosphamide.IC50 Value: 182 mM (decreased superoxide anion production stimulated with PMA (tetradecanoylphorbol acetate) in PMN in-vitro); 70mM (inhibited H2O2 production) [3]Target: in vitro: MESNA had no effect on the qualitative and quantitative characteristics of the indicated processes in both the types of the doxorubicin sensitive cells. The combined use of doxorubicin and phosphamide or cyclophosphane the use of MESNA for lowering the urotoxic action of oxazophosphorines had no effect on the biological efficacy of doxorubicin [4].in vivo: AMH-positive follicles were significantly decreased after cisplatin administration, which was significantly reversed when mesna was co-administered with cisplatin. The end product of lipid peroxidation, malondialdehyde (MDA), was significantly increased, but the anti-oxidative enzymatic activity of superoxide dismutase (SOD) and glutathione (GSH) were significantly decreased in cisplatin groups when compared with NS group. In contrast, after co-administration of cisplatin with mesna, MDA was significantly decreased whereas the activity of SOD and the concentration of GSH were increased. Moreover, mesna did not decrease the anti-tumor property of cisplatin in HePG2 cell lines [2]. After head trauma, tissue malondialdehyde levels increased; these levels were significantly decreased by MESNA administration. Caspase-3 levels were increased after trauma, but no effect of MESNA was determined in caspase-3 activity [1].Clinical trial: Effects of Mesna on Homocysteine in Kidney Failure . Phase2
NVP-BVU972 is a selective and potent Met inhibitor (IC50 = 14 nM). Antitumor agents.IC50 value: 14 nM [1]Target: MetNVP-BVU972 potently inhibits MET kinase but displays low inhibition against other kinases including the most closely related kinase RON with IC50 values of more than 1000 nM. NVP-BVU972 also suppresses constitutive MET phosphorylation in GTL-16 cells or HGF-stimulated MET phosphorylation in A549 cells with IC50 values of 7.3 nM and 22 nM, respectively. NVP-BVU972 potently prevents the growth of the MET gene amplified cell lines GTL-16, MKN-45 and EBC-1 with IC50 values of 66 nM, 82 nM and 32 nM, respectively. In line with their high frequency in the NVP-BVU972 screen, Y1230 and D1228 mutations give rise to dramatic shifts in the measured IC50 values for NVP-BVU972 in BaF3 cell line. Resistance triggered by V1155L is more limited to NVP-BVU972. A dose-dependent reduction in TPR-MET phosphorylation when applying NVP-BVU972 to BaF3 cells expressing wild-type TPR-MET. Both Y1230H and D1228A mutations abrogated the effect of NVP-BVU972 but not AMG 458. However, F1200I and L1195V interferes with the potency of NVP-BVU972 to prevent TPR-MET phosphorylation.
TNF-α-IN-1 is a TNF-α inhibitor extracted from patent US20030096841A1, compound example I-7.