pro-tumor

N-Nitroso-N-methylurea (NMU/MNU/NMH) is a nitrosourea compound with alkylating, carcinogenic, and mutagenic properties; as a direct-acting alkylating agent, it interacts with DNA and targets multiple animal organs to induce various cancers and degenerative diseases, and is commonly used to induce disease models such as gastric cancer and breast cancer in mice.

RBN012759 inhibits PARP14 protein with an IC50 value of 0.003 μM and is more than 300-fold selective over all PARP family members.[2]

BAY-218 is an aryl hydrocarbon receptor (AHR) antagonist with IC50 of 39.9 nM in the human glioblastoma U87 cell line. BAY-218 inhibition of AhR stimulates pro-inflammatory monocyte and T cell responses in vitro and drives anti-tumor immune responses, leading to reduced tumor growth in vivo.

A-802715 is a novel methylxanthine derivative that decreases the endogenous formation and blood levels of pro-inflammatory substances and increases the formation and blood levels of anti-inflammatory substances such as interleukin 10 receptor and tumor necrosis factor receptor.

SU11652 is an effective and competitive receptor tyrosine kinase (RTK) inhibitor, including VEGFR, FGFR, PDGFR, and Kit. SU11652 disrupts the function of all forms of mutant Kit and may be used in the study of cancers involving Kit mutations.

CP 461 (UNII-68OJX9I7DT), a specific PDE2A inhibitor, is a novel pro-apoptotic compound that inhibits cyclic GMP phosphodiesterase but not cyclooxygenase-1 or -2. CP 461 inhibits the growth of a variety of human tumor cell lines in vitro and selectively induces apoptosis in cancer cell lines, but not in normal cells.

Rofecoxib (MK 966) binds to and inhibits the enzyme cyclooxygenase-2 (COX-2), resulting in an inhibition of the conversion of arachidonic acid to prostaglandins. Rofecoxib is a synthetic, nonsteroidal derivative of phenyl-furanone with anti-inflammatory, antipyretic and analgesic properties and potential antineoplastic properties. COX-related metabolic pathways may represent key regulators of cell proliferation and neo-angiogenesis. Some epithelial tumor cell types overexpress pro-angiogenic COX-2.

1. Linalool (Linalol), a natural compound of the essential oils, has been shown to have antinociceptive, antimicrobial, and anti-inflammatory properties. 2. Linalool was protected against LPS/GalN-induced liver injury through induction of antioxidant defense via Nrf2 activating and reduction inflammatory response via NF-κB inhibition. 3. Linalool biosynthesis and accumulation might be involved in plant defense against bacterial and fungal pathogens and be associated with field resistance to citrus canker. 4. Linalool significantly increased the expression of antioxidant enzymes regulated by Nrf-2 and diminished lung tissue levels of several pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin (IL)-6.

NSC-37445 has anti-tumor activity, such as inhibits growth of bladder tumor cells in a nude mice model , prevents the recurrence and progression of non-muscle-invasive urothelial cell carcinoma. NSC-37445 can significantly reduce the expression of CDK1-inhibitory kinases, Myt1 and Wee1, and cause cyclin B1 protein accumulation leading to CDK1 activation in T24 cells. 3. Flavokawain A (Flavokavain A) may exert anti-inflammatory responses by suppressing LPS-induced expression of pro-inflammatory mediators via blockage of NF-κB-AP-1-JNK/p38 MAPK signaling pathways in the murine macrophages.

ABzOH is a benzoic acid derivative, similar in structure to non-steroidal anti-inflammatory drugs such as aspirin, with anti-inflammatory, anti-tumor and anti-proliferative effects. ABzOH can not only inhibit the expression of tumor necrosis factor-α (TNF-a), interleukin-1β (IL-1β), interleukin-6 (IL-6) and other pro-inflammatory cytokines, but also inhibit breast cancer, lung cancer and pancreatic cancer.

BI605906 is an IKKβ inhibitor that inhibits tumor necrosis factor alpha-dependent IkappaB degradation and expression of the pro-inflammatory mediator interleukin-6, which can be used to study inflammatory skin diseases such as psoriasis.

MKC8866 is a selective IRE1 RNase inhibitor (IC50: 0.29 μM in human vitro). MKC8866 inhibits IRE1 RNase in breast cancer cells leading to the decreased production of pro-tumorigenic factors and it can inhibit prostate cancer (PCa) tumor growth.

STAT3-IN-31 (compound K2071), derived from STATtic, acts as an inhibitor of both STAT3 and mitotic processes. This compound interrupts mitotic progression and impacts the formation of the mitotic spindle. Additionally, STAT3-IN-31 hampers migration in glioblastoma cells, suppresses cellular proliferation within tumor spheroids, induces senescence in glioblastoma, and inhibits the growth of Temozolomide-resistant cells while reducing the secretion of the pro-inflammatory cytokine monocyte chemoattractant protein (MCP-1).

DPP-21 is an inhibitor of microtubule protein polymerization (IC50: 2.4 μM). It exhibits antiproliferative activity against various cancer cell lines, with IC50 values of 0.38 nM (HCT116), 11.69 nM (B16), 5.37 nM (HeLa), 9.53 nM (MCF7), 8.94 nM (H23), and 9.37 nM (HepG2). DPP-21 induces cell cycle arrest at the G2/M phase of mitosis and subsequently triggers apoptosis in tumor cells by decreasing Bcl-2 while increasing pro-apoptotic protein Bax levels.

06:0 PE (PE(6:0/6:0)) is a water-soluble phospholipid characterized by its short acyl chains. It possesses notable antitumor activity and can inhibit tumor progression in the body. Additionally, it exhibits antiproliferative and pro-apoptotic properties, and serves as a precursor for phosphatidylcholine and phosphatidylethanolamine.

PLD-IN-1 (Compound 3r) is an orally effective inhibitor of phospholipase D (phospholipaseD) with an IC50 of 1.97 μM. It reduces the expression of CD24, CD47, and PD-L1 while enhancing the expression of calreticulin, thereby modulating the immune evasion mechanisms of lung cancer cells by promoting the phagocytosis of cancer cells by macrophages. PLD-IN-1 inhibits the viability of lung cancer cell lines A549, HCC44, H460, and HCC15 with IC50 values of 18.44, 22.31, 24.85, and 21.45 μM, respectively. It induces apoptosis (apoptosis) in A549 cells and inhibits cell migration. Additionally, PLD-IN-1 increases pro-inflammatory M1 macrophage levels and decreases anti-inflammatory M2 macrophage levels, exhibiting anti-tumor activity in mouse models.

AZD5991 is a potent and selective Mcl-1 inhibitor aimed at treating hematological cancers. As a well-designed macrocyclic compound, AZD5991 exhibits sub-nanomolar affinity for Mcl-1. It primarily inhibits the myeloid cell leukemia-1 protein (Mcl-1; Bcl2-L-3), showing potential pro-apoptotic and anti-tumor activity. AZD5991 binds to Mcl-1, preventing its interaction with certain pro-apoptotic proteins, leading to apoptosis in cells overexpressing Mcl-1.

Δ8-Tetrahydrocannabinoquinone (HU-336) is a potent anti-angiogenic agent that inhibits angiogenesis by directly inducing apoptosis in vascular endothelial cells. It achieves this without altering the expression of pro-angiogenic and anti-angiogenic cytokines and receptors. Δ8-Tetrahydrocannabinoquinone also shows significant effectiveness against tumor xenografts in nude mice.

CB2 receptor agonist 8 (Compound 17) is an agonist of the cannabinoid receptor 2 (CB2 receptor). It shows cytotoxicity in U87, RPMI 8226, HL-60, and L929 cells with IC50 values of 91.03, 16.29, 23.51, and 564.6 μM, respectively. CB2 receptor agonist 8 activates caspase 3/7, increases the expression of pro-apoptotic genes BAX, BAD, BIM, and the tumor suppressor gene p53, and induces apoptosis in U87 cells. Additionally, it inhibits the migration of U87 cells.

TopoisomeraseI inhibitor 17 (Compound 7h) is an inhibitor of TopoisomeraseI (Top1). It reduces DDX5 and reverses the locking effect of DDX5 on Top1 activity. This compound induces Top1-mediated DNA damage and promotes reactive oxygen species (ROS) production. It triggers apoptosis by decreasing anti-apoptotic proteins XIAP, Bcl-2, and Survivin, while increasing pro-apoptotic proteins Bax and γH2AX. Moreover, TopoisomeraseI inhibitor 17 halts progression at the G2/M checkpoint, leading to cell cycle arrest. It significantly impairs colorectal cancer cell colony formation and migration, and effectively reduces tumor size in human PDX tumor mouse models.

Anti-TNBC agent-9 (Compound 3as) is an anticancer agent used for treating triple-negative breast cancer (TNBC). It exhibits significant inhibitory activity against MDA-MB-453 cells, with an IC50 value of 8.5 μM. Anti-TNBC agent-9 impedes tumor cell migration by upregulating E-cadherin and downregulating N-cadherin, matrix metalloproteinase 2 (MMP2), and MMP9. Additionally, it inhibits tumor cell proliferation by inducing apoptosis, achieved through the increased expression of pro-apoptotic protein BAX and decreased expression of anti-apoptotic protein BCL-2.

PARP14 inhibitor2 (Compound 3) is an orally active and highly selective PARP14 inhibitor with an IC50 value of less than 30 nM. It effectively inhibits the mono ADP-ribosyltransferase activity of PARP14 and modulates IFN-γ and IL-4 signaling, thereby reversing pro-tumor macrophage polarization and suppressing anti-tumor inflammatory responses. PARP14 inhibitor2 holds potential for research in PARP14-related conditions such as tumors, atopic dermatitis, and autoimmune diseases.

Pro-905 is a phosphonate peptide with antitumor activity. It delivers the active nucleotide antimetabolite thioinosine monophosphate (TGMP) to tumors. Pro-905 effectively inhibits the binding of purine residue substrates to nucleic acids, thereby suppressing colony formation of human malignant peripheral nerve sheath tumor (MPNST) cells. It prevents purine residues from incorporating into nucleic acids, hindering cell growth. Additionally, Pro-905 inhibits the growth of MPNST and enhances the antitumor effect of JHU395.

pro-FTY is an anticancer prodrug of FTY720 and acts as a sphingosine-1-phosphate (S1P) inhibitor. It specifically inhibits S1P signaling in cancer cells via a drug delivery system (DDS) that reacts with acrolein. pro-FTY significantly reduces the survival of breast cancer cells, including multidrug-resistant cells and organoids resistant to Paclitaxel or Doxorubicin. Additionally, pro-FTY effectively suppresses tumor growth in xenograft mouse models of 4T1 cells or organoids while avoiding lymphopenia.