osteosarcoma

Osteosarcoma-IN-D14 is an inhibitor of migration and invasion of osteosarcoma cells mediated by p53, regulating EMT-related genes.

Deracoxib (SC 46) is a non-steroidal, non-narcotic anti-inflammatory drug. It is also a selective cyclooxygenase-2 inhibitor, and IC50 Value: 70 to 150 μM(inhibition of 3 osteosarcoma cell lines).

Mifamurtide is a drug against osteosarcoma, is an immunomodulator with antitumor effects.

Calycosin (Cyclosin) acts as a selective estrogen receptor modulator. Calycosin induces apoptosis in human ovarian cancer SKOV3 cells by activating caspases and Bcl-2 family proteins. Calycosin suppresses breast cancer cell growth via ERβ-dependent regulation of IGF-1R, p38 MAPK and PI3K/Akt pathways. Calycosin has antineoplastic effects against osteosarcoma through inducing apoptosis showing in vitro and in vivo investigations. Calycosin was shown to induce angiogenesis in human umbilical vein endothelial cell cultures (HUVEC) in vitro. Calycosin may be an effective skin-lightening agent that regulates the expression of melanogenic enzymes. Calycosin exhibited tyrosinase inhibitory activity with an IC(50) value of 38.4 microM.

Columbamine (Columbamin) shows strong activity with IC5 48.1 μM.Columbamine exerts anti-proliferative and anti-vasculogenic effects on metastatic human osteosarcoma U2OS cells with low toxicity.

1. Daphnoretin (Thymelol) has strong antiviral activity, mainly on the later phase of the replication cycle. 2. Daphnoretin has anticancer effects on leukemia, osteosarcoma and uterine cervix cancer cells, might through promoting apoptosis in a mitochondria-mediated way. 3. Daphnoretin causes death of HOS cells by blocking cells successively in G2/M phases and activating the caspase-3 pathway.

TMPyP4 tosylate (TMP 1363) is a quadruplex-specific ligand and telomerase inhibitor that exhibits antitumor effects in osteosarcoma cell lines.

BMS-986122 (BMS 986122) is a positive allosteric modulator of μ-opioid receptors that increases β-arrestin recruitment stimulated by endomorphin 1 in U2OS-OPRM1 human osteosarcoma cells expressing μ-opioid receptors (EC50 = 3 μM).

WM-3835 is a novel and high-specific small molecule inhibitor of Lysine Acetyltransferase 7 (KAT7, MYST2, HBO1) , able to potently suppressed OS cell proliferation and migration, and leads to apoptosis activation.

AZ-Dyrk1B-33 (3-(2-Methyl-4-pyrimidinyl)-1-(phenylmethyl)-1H-pyrrolo[2,3-c]pyridine) is a potent and selective Dyrk1B kinase inhibitor with an IC50 of 7 nM.

2-deoxy-2-fluoro-D-Glucose (2-FG) is a derivative of glucose with anticancer activity.1It inhibits the growth of 143B osteosarcoma cells grown under normoxic and hypoxic conditions when used at concentrations of 6 and 24 mM.

2-deoxy-D-Glucose-13C6is intended for use as an internal standard for the quantification of 2-deoxy-D-glucose by GC- or LC-MS. 2-deoxy-D-Glucose is a glucose antimetabolite and an inhibitor of glycolysis.1,2It inhibits hexokinase, the enzyme that converts glucose to glucose-6-phosphate, as well as phosphoglucose isomerase, the enzyme that converts glucose-6-phosphate to fructose-6-phosphate.32-deoxy-D-Glucose (16 mM) induces apoptosis in SK-BR-3 cells, as well as inhibits the growth of 143B osteosarcoma cells cultured under hypoxic conditions when used at a concentration of 2 mg/ml.4,5In vivo, 2-deoxy-D-glucose (500 mg/kg) reduces tumor growth in 143B osteosarcoma and MV522 non-small cell lung cancer mouse xenograft models when used alone or in combination with doxorubicin or paclitaxel .6 1.Kang, H.T., and Hwang, E.S.2-Deoxyglucose: An anticancer and antiviral therapeutic, but not any more a low glucose mimeticLife Sci.78(12)1392-1399(2006) 2.Aft, R.L., Zhang, F.W., and Gius, D.Evaluation of 2-deoxy-D-glucose as a chemotherapeutic agent: Mechanism of cell deathBr. J. Cancer87(7)805-812(2002) 3.Ralser, M., Wamelink, M.M., Struys, E.A., et al.A catabolic block does not sufficiently explain how 2-deoxy-D-glucose inhibits cell growthProc. Natl. Acad. Sci. USA105(46)17807-17811(2008) 4.Liu, H., Savaraj, N., Priebe, W., et al.Hypoxia increases tumor cell sensitivity to glycolytic inhibitors: A strategy for solid tumor therapy (Model C)Biochem. Pharmacol.64(12)1745-1751(2002) 5.Zhang, X.D., Deslandes, E., Villedieu, M., et al.Effect of 2-deoxy-D-glucose on various malignant cell lines in vitroAnticancer Res.26(5A)3561-3566(2006) 6.Maschek, G., Savaraj, N., Priebe, W., et al.2-deoxy-D-glucose increases the efficacy of adriamycin and paclitaxel in human osteosarcoma and non-small cell lung cancers in vivoCancer Res.64(1)31-34(2004)

Naxitamab (Hu3F8) is a humanized monoclonal antibody targeting GD2 with antitumor activity, used to study neuroblastoma, osteosarcoma, and other GD2-positive cancers.

BRC4wt, an acetylated peptide originating from the BRC4 repeat within human BRCA2 (1521-1536), acts as an inhibitor of the BRCA2 and RAD51 protein-protein interaction. When linked to the cationic cell-penetrating peptide (Arg)9, it effectively shortens DNA replication tract lengths and diminishes the frequency of homologous repair of camptothecin-induced DNA damage in vitro. Additionally, BRC4wt enhances the efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib in inducing cell death in HeLa human cervical cancer and U2OS human osteosarcoma cells, albeit it does not affect non-cancerous hTERT RPE-1, MRC-5, or MCF-10A cells.

AM-6761 is a potent inhibitor of the MDM2-p53 interaction. In the SJSA-1 osteosarcoma xenograft model, AM-6761 shows excellent antitumor activity with an ED50 of 11 mg/kg.

KRH102140 is a potent activator of PHD2. KRH102140, which has a structure similar to KRH102053. KRH102140 more efficiently suppressed HIF-1α than KRH102053 in human osteosarcoma cells under hypoxia. Furthermore, KRH102140 decreased the mRNA levels of HIF-regulated downstream target genes associated with angiogenesis and energy metabolism such as vascular endothelial growth factor, adrenomedullin, Glut1, aldolase A, enolase 1 and monocarboxylate transporter 4. KRH102140 also inhibited tube formation in human umbilical vein endothelium cells. The results suggest that KRH102140 has potential therapeutic effects in alleviating various diseases associated with HIFs.

1. Ganoderic acid A exhibits antitumor activity, mediated through its inhibitory effect on nuclear transcription factor-kappaB and activator protein-1. 2. Ganoderic acid A can induce proliferation inhibition, apoptosis and suppression of invasion in human

Raddeanin A (NSC-382873) has moderate inhibitory activity against histone deacetylases (HDACs). Raddeanin A has high antiangiogenic potency, antitumor activity.

PDGFR-IN-1 (compound 7m) is an orally active PDGFR (platelet-derived growth factor receptor) inhibitor that targets PDGFRα (IC50: 2.4 nM) and PDGFRβ (IC50: 0.9 nM), exhibiting strong anti-tumor effects and low toxicity, making it suitable for osteosarcoma studies.

1. Steviol (NSC-226902), a natural sweetener, it inhibits proliferation of the gastrointestinal cancer cells intensively. 2. Steviol can induce a significant increase in CYP3A29 expression. 3. Steviol inhibits the proliferation of the human osteosarcoma U2OS cell line in a dose- and time-dependent manner. 4. Steviol can treat polycystic kidney disease, it slowed cyst growth, in part, by reducing AQP2 transcription, promoted proteasome, and lysosome-mediated AQP2 degradation.

KSQ-4279 (USP1-IN-1) is an inhibitor of USP1 and PARP, exhibiting anticancer activity. It is utilized in the study of non-small cell lung cancer, osteosarcoma, ovarian, breast, glioblastoma, bladder, uterine, and pancreatic cancers.

YW3-56 is an inhibitor of protein arginine deiminase 2 (PAD2) and PAD4 (IC50s = 0.5-1 and 1-5 μM, respectively).1It inhibits the growth of U2OS osteosarcoma cells (IC50= ~2.5 μM) in a p53-dependent mannerviainduction of SESN2 and subsequent inhibition of mTORC1. YW3-56 (10 mg/kg) reduces tumor growth in an S-180 murine sarcoma tumor model. It also inhibits tumor growth in the 1883 MDA-MB-231 breast cancer bone metastasis mouse xenograft model.2 1.Wang, Y., Li, P., Wang, S., et al.Anticancer peptidylarginine deiminase (PAD) inhibitors regulate the autophagy flux and the mammalian target of rapamycin complex 1 activityThe Journal of Biological Chemisty287(31)25941-25952(2012) 2.Wang, S., Chen, X.A., Hu, J., et al.ATF4 gene network mediates cellular response to the anticancer PAD inhibitor YW3-56 in triple-negative breast cancer cellsMol. Cancer Ther.14(4)877-888(2015)

Zoledronate disodium is an inhibitor of osteoclastogenesis and macrophage recruitment, decreasing bone turnover and stabilizing the bone matrix, exhibiting diverse anti-tumor effects in osteosarcoma.

MSC-4381 (MCT4-IN-1) is an orally available and selectively modeled highly potent inhibitor of monocarboxylic acid transporter protein 4 (MCT4/SLC16A3) with potential anticancer and antitumor activity for the study of osteosarcoma.

Mifamurtide TFA (MTP-PE TFA), a muramyl dipeptide (MDP) analog, acts as a nonspecific immunomodulator by activating macrophages and monocytes to stimulate the immune response. As an orphan agent and a specific NOD2 ligand, it is utilized as an insulin sensitizer and holds research potential in osteosarcoma [1][2][3].

Robatumumab (Sch 717454), an anti-human insulin-like growth factor receptor-1 (IGF-1R) antibody, exhibits anti-tumor and anti-proliferative effects on cancer cells. It is applicable in research concerning osteosarcoma and Ewing sarcoma [1] [2].

Socazolimab (ZKAB001), an anti-PD-L1 monoclonal antibody, demonstrates enduring safety and efficacy in treating recurrent or metastatic cervical cancer. Additionally, it shows promise for treating small cell lung cancer, esophageal squamous cell carcinoma (ESCC), advanced urothelial carcinoma, and osteosarcoma [1] [2] [3] [4] [5].

Neogrifolin is a potential candidate for osteosarcoma, it can induce concentration- and time-dependent suppression of proliferation and induce apoptosis in U2OS and MG63 osteosarcoma cell lines; it exhibits inhibitory activity against nitric oxide (NO) production stimulated by lipopolysaccharide (LPS) in RAW 264.7 cells with the IC50value of 23.3 microM. Neogrifolin possesses antimicrobial activities against Bacillus cereus and Enterococcus faecalis, the MIC values of 20 and 0.5 microg/mL, respectively.

DC_AC50 is a dual inhibitor of Atox1 and CCS (copper chaperones), aimed at reducing or preventing acquired chemotherapy resistance by inhibiting intracellular copper chaperones. It binds to Atox1 and CCS, thereby reducing cancer cell proliferation and tumor growth.

Mifamurtide sodium is a drug against osteosarcoma, a kind of bone cancer mainly affecting children and young adults. It was approved in Europe in March 2009.

Seocalcitol is an analog of vitamin D, binds vitamin D receptor protein from human osteosarcoma MG-63 cells(Kd : 0.27 nM).

(±)19(20)-EDP ethanolamide is an ω-3 endocannabinoid epoxide and cannabinoid (CB) receptor agonist (EC50s = 108 and 280 nM for CB1 and CB2, respectively). It is produced through direct epoxygenation of docosahexaenoyl ethanolamide by cytochrome P450 (CYP) epoxygenases. (±)19(20)-EDP ethanolamide (25 μM) reduces the viability of 143B metastatic osteosarcoma cells. It decreases the production of IL-6 and increases the production of IL-10 when used at concentrations ranging from 2.5 to 10 μM in BV-2 microglia stimulated by LPS and decreases LPS-induced cytotoxicity when used at concentrations ranging from 5 to 10 μM. It also decreases nitrite production when used at a concentration of 7.5 μM, an effect that can be partially reversed by the CB2 receptor antagonist AM630 and the PPARγ antagonist GW 9662 . (±)19(20)-EDP ethanolamide induces vasodilation of isolated preconstricted bovine coronary arteries (ED50 = 1.9 μM) and reduces tube formation by human microvascular endothelial cells (HMVECs) in a Matrigel assay.

Antitumor agent-51 is effective and selective in inhibiting the growth and migration of osteosarcoma cells, acting on MNNG/HOS cells (IC50: 21.9 nM). antitumor agent-51 is less toxic and extremely bioavailable.

1. Coptisine (Coptisin) treatment increases cell viability based on its reversal effect on the enhanced activity of Indoleamine 2, 3-dioxygenase . 2. Coptisine treats myocardial I/R likely through suppressing myocardial apoptosis and inflammation by inhibiting the Rho/ROCK pathway. 3. Coptisine is a potential anti-osteosarcoma drug candidate, via exerting a strong anti-osteosarcoma effect with very low toxicity . 4. Coptisine with a high dosage could inhibit cholesterol synthesis via suppressing the HMGCR expression and promoting the use and excretion of cholesterol via up-regulating LDLR and CYP7A1 expression. 5. Coptisine suppresses adhesion, migration and invasion of MDA-MB-231 breast cancer cells in vitro, the down-regulation of MMP-9 in combination with the increase of TIMP-1 possibly contributing to the anti-metastatic function for breast cancer.

Pterostilbene-isothiocyanate (PTER-ITC) demonstrates strong anticancer properties in vitro, particularly disrupting the interaction between β-catenin and TCF-4 in human osteosarcoma cells [1].

Capillarisin is a novel blocker of STAT3 activation and thus may have a potential in negative regulation of growth, metastasis, and chemoresistance of tumor cells, it inhibits cancer cell growth of osteosarcoma cells by inducing apoptosis accompanied with

Cdk2 Cyclin Inhibitory Peptide II (Tat-LDL), a CDK2 inhibitor, exhibits dose-dependent cytotoxic effects on U2OS osteosarcoma cells [1].

S 14063 is a potent 5-HT1A receptor antagonist devoid of beta-adrenoceptor blocking properties.

(±)10(11)-EDP ethanolamide is an ω-3 endocannabinoid epoxide and cannabinoid (CB) receptor agonist (EC50s = 0.43 and 22.5 nM for CB1 and CB2 receptors, respectively). It is produced though direct epoxygenation of docosahexaenoyl ethanolamide by cytochrome P450 (CYP) epoxygenases. 10,11-EDP epoxide (12.5 and 25 μM) reduces the viability of 143B metastatic osteosarcoma cells. It induces apoptosis and inhibits cell migration in a wound-healing assay in 143B, MG63, and HOS osteosarcoma cells. (±)10(11)-EDP ethanolamide also reduces tube formation by human umbilical vein endothelial cells (HUVECs) in a Matrigel assay.

Chamaejasmine could be a candidate drug for osteosarcoma and breast cancer chemoprevention, induces apoptosis in MG63 and HEp-2 cells by Akt inactivation and dephosphorylation of BAD. It inhibits Bcl-2 expression and induces Bax expression to desintegrate

Gemcitabine-ibandronate (GEM–IB), a conjugate of gemcitabine (GEM)-5'-phosphate with ibandronate (IB), exhibits efficacy both as a monotherapy and synergistically with Docetaxel (DTX), resulting in diminished tumor burden, maintained bone structure, and enhanced survival in a murine osteosarcoma (OS) model [1].

CYY292 is a chemical compound acting as an inhibitor of PDGFRα, PDGFRβ, FGFR1, -2, and -3, with respective IC50 values of 5.35, 4.6, 28, 28, and 78 nM. It exhibits selectivity over FGFR4 (IC50 > 1,000 nM) while also targeting c-Kit, VEGFR2, VEGFR1, and IGF-1R (IC50 values of 67, 33, 36, and 75 nM, respectively). Additionally, CYY292 inhibits EGFR, BTK, Cdk4/cyclin D3, and MET with IC50 values of 128, 198, 214, and 396 nM, respectively. This compound demonstrates efficacy in arresting the proliferation of various osteosarcoma cell lines—MG-63, U2OS, MNNG/HOS, and Saos-2—with IC50s ranging from 0.72 to 1.36 µM. Moreover, CYY292 at 0.3 and 0.5 µM concentrations inhibits migration and invasion in glioblastoma cells (U87MG and LN-229) and, at a dose of 30 mg/kg, decreases tumor volume and enhances survival in a U87MG orthotopic mouse xenograft model.

Polyphyllin G (Polyphyllin VII), the the main member of polyphyllin family, shows strong anticancer activity against several carcinomas, including lung cancer, breast cancer, colorectal cancer, cervical cancer, hepatocellular carcinoma and osteosarcoma.

Osteocalcin (1-49) is a non-collagenous peptide that is secreted by osteoblasts and odontoblasts and comprises 1-2% of the total protein in bone. Secretion of osteocalcin (1-49) is stimulated by 1,25-dihydroxy vitamin D and plasma levels increase in diseases that induce dysregulated bone turnover such as osteoporosis, Paget's disease, and primary hyperparathyroidism. Osteocalcin (1-49) is positively correlated with insulin sensitivity and negatively correlated with high blood glucose levels in women. In vitro, osteocalcin induces chemotaxis of MDA-MB-231 breast cancer cells, human peripheral blood monocytes, and rat osteosarcoma cells with osteoblast-like characteristics. It is also expressed by vascular smooth muscle cells (VSMCs) displaying an osteoblast-like phenotype and has been positively associated with calcification of aortic tissue and heart valves in humans.

Antitumor agent-50 (compound 1a) is a thiazolidinone. Antitumor agent-50 is an effective antitumor agent that has the potential for the research of osteosarcoma (OS) [1].

Selective HIF-1 dimerization inhibitor. Blocks protein-protein interaction of recombinant HIF-1α, but not HIF-2α, with HIF-1β (IC50 = 1.3 μM). Inhibits hypoxia-induced HIF-1 activity, and decreases VEGF and CAIX expression in osteosarcoma and breast cance