xenografts

Tasquinimod (ABR-215050) is a quinoline-3-carboxamide linomide analog with antiangiogenic and potential antineoplastic activities. Tasquinimod has been shown to decrease blood vessel density but the exact mechanism of action is not known. This agent has also been shown to augment the antineoplastic effects of docetaxel and androgen ablation in a murine model of prostate cancer involving human prostate cancer xenografts.

BFC1108 targets Bcl-2 and converts it to a pro-apoptotic protein, inhibits the growth of triple-negative breast cancer xenografts with high Bcl-2 expression, inhibits breast cancer lung metastasis, and induces apoptosis of Bcl-2-expressing cancer cells.

TH287 is a selective MTH1 inhibitor(IC50 : 0.8 nM). It causees incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts.

KW-2450 Formate is an IGF-1R/IR tyrosine kinase inhibitor with antitumor effects that acts through inhibition of Aurora A and B kinases.KW-2450 Formate inhibits the growth of TNBC xenografts and induces tetraploid accumulation.

PCI-27483 is an activated coagulation factor VIIa inhibitor with antithrombotic effects in a baboon model of arterial thrombosis. It also inhibits the growth of BxPC3 xenografts by 42% and 85% at doses of 60 and 90 mg/kg, respectively.

Famitinib (SHR1020) is a potent orally active multi-targeted kinase inhibitor that effectively inhibits the activity of c-kit, VEGFR-2, and PDGFRβ with IC50 values of 2.3 nM, 4.7 nM, and 6.6 nM, respectively [1]. It demonstrates remarkable antitumor properties in human gastric cancer cells and xenografts, inducing apoptosis [2].

OSI-296 is a potent and dual inhibitor of cMET and RON kinases (IC50 value are 42 nM and 200 nM for cMet and sfRon respectively) . OSI-206 shows in vivo efficacy and is well tolerated in tumor xenografts models upon oral dosing. OSI-296 also reduces tumou

Ensartinib (X-396) is a potent dual ALK MET inhibitor with IC50 values of <0.4 nM for ALK and 0.74 nM for MET.

BS194 is as a potent cyclin-dependent protein kinases (CDKs) inhibitor.

Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0/G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013). Nemorosone is a polycyclic polyprenylated acylphloroglucinol (PPAP) originally isolated from C. rosea that has antiproliferative properties.1 Nemorosone inhibits growth of NB69, Kelly, SK-N-AS, and LAN-1 neuroblastoma cells (IC50s = 3.1-6.3 μM), including several drug-resistant clones, but not MRC-5 human embryonic fibroblasts (IC50 = >40 μM).2 It increases DNA fragmentation in LAN-1 cells in a dose-dependent manner, and decreases N-Myc protein levels and phosphorylation of ERK1/2 by MEK1/2. Nemorosone also inhibits growth of Capan-1, AsPC-1, and MIA-PaCa-2 pancreatic cancer cells (IC50s = 4.5-5.0 μM following a 72-hour treatment) but not human dermal and foreskin fibroblasts (IC50s = >35 μM).1 It induces apoptosis, abolishes the mitochondrial membrane potential, and increases cytosolic calcium concentration in pancreatic cancer cells in a dose-dependent manner. Nemorosone activates the caspase cascade in a dose-dependent manner and inhibits cell cycle progression, increasing the proportion of cells in the G0/G1 phase, in both neuroblastoma and pancreatic cancer cells.1,2 Nemorosone (50 mg/kg, i.p., per day) also reduces tumor growth in an MIA-PaCa-2 mouse xenograft model.3 References1. Holtrup, F., Bauer, A., Fellenberg, K., et al. Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR). Br. J. Pharmacol. 162(5), 1045-1059 (2011).2. Díaz-Carballo, D., Malak, S., Bardenheuer, W., et al. Cytotoxic activity of nemorosone in neuroblastoma cells. J. Cell. Mol. Med. 12(6B), 2598-2608 (2008).3. Wold, R.J., Hilger, R.A., Hoheisel, J.D., et al. In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer xenografts. PLoS One 8(9), e74555 (2013).

NSC156529 downregulates AKT1 signaling. NSC156529 efficiently decreases the proliferation of human cancer cells in vitro, and substantially inhibits the growth of prostate tumor xenografts in vivo.

Malformin C is a natural fungus-derived bicyclic pentapeptide that has antibacterial properties, particularly against species of Bacillus. Malformin C potently blocks the ability of bleomycin to induce G2 arrest in human T-cell leukemia-derived Jurkat cells (IC50 = 0.9 nM). It less potently abrogates colchicine-induced M phase arrest in Jurkat cells (IC50 = 24 nM). Malformin C inhibits cell growth dose-dependently in Colon 38 and HCT 115 cancer cells (IC50s = 0.27 and 0.18 μM, respectively) but has a low therapeutic index against cancer xenografts when tested in mice.

TAK-960 monohydrochloride is an orally available compound that selectively inhibits polo-like kinase 1 (PLK1) with an IC₅₀ of 0.8 nM. It also demonstrates inhibitory activity against PLK2 (IC₅₀ of 16.9 nM) and PLK3 (IC₅₀ of 50.2 nM), and effectively suppresses the proliferation of various cancer cell lines, exhibiting significant efficacy against multiple tumor xenografts.

NU5455 is a selective, potent, orally active inhibitor of DNA-PKcs. It enhances the efficacy of locally released doxorubicin in liver tumor xenografts without causing adverse effects and also enhances the efficacy and toxicity of parenterally administered topoisomerase inhibitors.

EPZ020411 is a potent and selective PRMT6 inhibitor tool compound. EPZ020411 shows good bioavailability following subcutaneous dosing in rats making it a suitable tool for in vivo studies. EPZ020411 suppresses RCC1 arginine methylation and improves the cytotoxic activity of radiotherapy against GSC brain tumor xenografts.

CGC 11093 is a polyamine analog; inhibits growth of human prostate tumor xenografts in nude mice. It may prove useful in promoting regression of choroidal neovascularization.

1-Palmitoyl-d9-2-hydroxy-sn-glycero-3-PE serves as an internal standard for quantifying 1-palmitoyl-2-hydroxy-sn-glycero-3-PE, a lysophospholipid naturally found to inhibit L. donovani promastigotes growth (GI50= 8 µM). Its levels are reduced in mice after alcohol-induced liver damage, in hepatocellular carcinoma mouse xenografts, and in humans following a rigorous three-day exercise regimen of 2.5 hours running daily and 14 hours post-regimen. This compound is also applied in measuring saturated lysophosphoethanolamines, highlighting its broad utility in biochemical research and disease model studies.

CHD1Li 6.11 is a potent inhibitor of oncogenic CHD1L, acting on the cat-CHD1L recombinant protein (IC50: 3.3 μM). CHD1Li 6.11 is an orally active antitumour agent that significantly reduces the tumour volume of CRC xenografts generated from isolated quasi-mesenchymal cells (M phenotype) with enhanced tumourigenic properties. These cells have enhanced tumourigenic properties.

UCM05 (G28UCM) is a potent inhibitor of fatty acid synthase (FASN) with efficacy against HER2+ breast cancer xenografts, including cell lines resistant to anti-HER2 drugs [1]. Additionally, it functions as an inhibitor of the Filamentous temperature-sensitive protein Z (FtsZ), selectively inhibiting the growth of the Gram-positive bacterium B. subtilis with minimum inhibitory concentration (MIC) values of 100 μM, while showing no activity against the Gram-negative bacterium E. coli [2].

ZK53 is a selective and potent activator of mitochondrial casein hydrolase protease P (HsClpP).ZK53 induces apoptosis and inhibits the hydrolysis of alpha-casein by HsClpP.ZK53 inhibits tumour growth in xenografts and native mouse models.

LMP517 (NSC 781517), an indenoisoquinoline, is a potent dual TOP1 and TOP2 inhibitor that shows better antitumor activity than its parent compound LMP744 against H82 (Small Cell Lung Cancer) xenografts, inducing TOP1 cleavage complexes (TOP1ccs) and TOP2ccs [1].

CP681301 is a potent inhibitor of CDK5 with antiproliferative activity. CP681301 exhibits anti-tumor activity in Drosophila. CP681301 decreases the expression of CD133, OLIG2, SOX2, KI67, pCDK5 protein level in Glioma stem cells (GSCs). CP681301 reduces self-renewal in mouse glioma xenografts [1].

IRC-083927 HCl is novel and potent microtubule inhibitor with potential anticancer activity. IRC-083927 inhibits the tubulin polymerization by a binding to the colchicine site. IRC-083927 inhibits in vitro cell growth of human cancer cell lines in the low nanomolar range. More interesting, it remains highly active against cell lines resistant to microtubule-interacting agents (taxanes, Vinca alkaloids, or epothilones). Chronic oral treatment with IRC-083927 (5 mg/kg) inhibits the growth of two human tumor xenografts in nude mice (C33-A, human cervical cancer and MDA-MB-231, human hormone-independent breast cancer). Together, the antitumor effects induced by IRC-083927 on tumor models resistant to tubulin agents support further investigations to fully evaluate its potential for the treatment of advanced cancers, particularly those resistant to current clinically available drugs.

GB1874 inhibitor of the Wnt pathway that targets the β-cat-TCF4 PPI. GB1874 also affected the proliferation and stemness of Wnt-addicted colorectal cancer (CRC) cells in vitro. Encouragingly, GB1874 inhibited the growth of CRC tumor xenografts in vivo, thus demonstrating its potential for further development into therapeutics against Wnt-associated cancer indications.

A 74932 is a quinolone antibacterial agent and inhibitor of topoisomerase II enzyme. A-74932 possesses good activity in vivo against both systemic tumour, subcutaneously implanted murine solid tumours and human tumour xenografts.

Atiratecan (TP300) is a prodrug of camptothecin analog CH0793076. Atiratecan shows antitumor activity against both breast cancer resistance protein (BCRP)-positive and -negative xenografts in mouse xenograft models[1]. Atiratecan does not inhibit acetylch

Xylocydine is a novel Cdk inhibitor, which is an effective inducer of apoptosis in hepatocellular carcinoma cells in vitro and in vivo. Xylocydine also strongly inhibits the activity of Cdk7 and Cdk9, in vitro as well as in cell cultures, that is temporally associated with apoptotic cell death in xylocydine-induced HCC cells. Xylocydine can effectively suppress the growth of HCC xenografts in Balb/C-nude mice by preferentially inducing apoptosis in the xenografts, whereas the drug did not cause any apparent toxic effect on other tissues.Xylocydine is a good candidate for an anti-cancer drug for HCC therapy.

JAS239 is a novel carbocyanine dye that binds and competitively inhibits choline kinase (ChoK) intracellularly. JAS239 attenuated choline phosphorylation and viability in a panel of human breast cancer cell lines. Antibody blockade prevented cellular retention of JAS239 indicating direct interaction with ChoKα independent of the choline transporters and catabolic choline pathways. In mice bearing orthotopic MCF7 breast xenografts, optical imaging with JAS239 distinguished tumors overexpressing ChoKα from their empty vector counterparts and delineated tumor margins.

LGB-321 is a potent and selective ATP-competitive small molecule inhibitor of PIM kinases (Pan-PIM kinase inhibitor). LGB321 is unique relative to previously described PIM inhibitors, in that it is active in PIM2 dependent cell lines. , a kinase that has proven difficult to inhibit in the cellular context. Consistent with its activity on all three PIM kinases, LGB321 inhibits proliferation of a number of cell lines derived from diverse hematological malignancies, including MM, AML, CML and B-Cell NHL. In vivo, LGB-321 is orally available, demonstrates efficacy in tumor xenografts and is well-tolerated within the therapeutic exposure range in mice. (source: Clin Cancer Res. 2014 Apr 1;20(7):1834-45 )

DIM-C-pPhOH (CDIM8) is a nur77 (NR4A1) antagonist,inhibits TGF-β induced cell migration of breast cancer cell lines,promotes ROS/endoplasmic reticulum stress and proapoptotic pathways in pancreatic cancer cell lines,mimics effects of Nur77 RNAi silencing.

PROTAC_ERRalpha is a proteolysis targeting chimeras (PROTAC) which provides broad tissue distribution and knockdown of the targeted ERRalpha protein in tumor xenografts.

MeTC7 is a VDR antagonist, which can be synthesized from 7-dehydrocholesterol (6) in two steps, inhibits VDR selectively, suppresses the viability of cancer cell-lines, and reduces the growth of the spontaneous transgenic TH-MYCN neuroblastoma and xenografts in vivo.

Sigma-2 Radioligand 1 (compound 1) serves as a selective Sigma-2 ligand, demonstrating favorable biodistribution in mice and robust in vivo activity in rats. The [18F] modified version of Sigma-2 Radioligand 1 enhances the visualization of tumors in micro-PET CT imaging by providing high tumor uptake and an impressive tumor-to-background ratio. Additionally, experiments confirm that this compound binds with high specificity to U87MG glioma xenografts [1].

Coibamide A, an N-methyl-stabilized cytotoxic depsipeptide, exhibits potent antiproliferative activity, induces autophagosome accumulation via an mTOR-independent mechanism, and triggers apoptosis. Furthermore, it inhibits VEGFA VEGFR2 expression, effectively suppressing tumor growth in glioblastoma xenografts [1] [2].

Famitinib malate (SHR1020) is an orally active multi-targeted kinase inhibitor that effectively inhibits the activity of c-kit, VEGFR-2, and PDGFRβ with IC50 values of 2.3 nM, 4.7 nM, and 6.6 nM, respectively. It induces cell apoptosis and demonstrates potent antitumor activity in human gastric cancer cells and xenografts, making it a valuable compound for cancer research.

STA-1474 is a water soluble prodrug of ganetespib (formerly STA-9090). STA-1474 will metabolized to Ganetespib, which is a potent HSP90 inhibitor previously shown to kill canine tumor cell lines in vitro and inhibit tumor growth in the setting of murine xenografts. The purpose of the following study was to extend these observations and investigate the safety and efficacy of STA-1474 in dogs with spontaneous tumors.

TAK-960 dihydrochloride is an orally administered, selective polo-like kinase 1 (PLK1) inhibitor with a potent IC50 of 0.8 nM. It also targets PLK2 and PLK3 with IC50 values of 16.9 and 50.2 nM, respectively. This compound effectively inhibits the proliferation of a broad range of cancer cell lines and demonstrates substantial efficacy against various tumor xenografts.

PKI-179 is a potent, orally active compound that functions as a dual PI3K mTOR inhibitor. It demonstrates IC50 values of 8 nM for PI3K-α, 24 nM for PI3K-β, 74 nM for PI3K-γ, 77 nM for PI3K-δ, and 0.42 nM for mTOR. Additionally, it is effective against E545K and H1047R mutations, with IC50s of 14 nM and 11 nM, respectively. In vivo studies have shown that PKI-179 possesses anti-tumor capabilities[1][2].

BMS-554417 is a novel inhibitor of IGF-IR, which inhibits IGF-IR and insulin receptor kinase activity and proliferation in vitro, and reduces tumor xenograft size in vivo. In a series of carcinoma cell lines, the IC50 for proliferation ranged from 120 nmol/L (Colo205) to >8.5 micromol/L (OV202). BMS-554417 treatment inhibited IGF-IR and insulin receptor signaling through extracellular signal-related kinase as well as the phosphoinositide 3-kinase/Akt pathway, as evidenced by decreased Akt phosphorylation at Ser473. At doses that inhibited proliferation, the compound also caused a G0-G1 arrest and prevented nuclear accumulation of cyclin D1 in response to LR3 IGF-I. In Jurkat T-cell leukemia cells, this agent triggered apoptotic cell death via the mitochondrial pathway. BMS-554417 was orally bioavailable and significantly inhibited the growth of IGF1R-Sal tumor xenografts in vivo. BMS-554417 is a member of a novel class of IGF-IR/insulin receptor inhibitors that have potential......

OH-Chol is a cationic cholesterol derivative. OH-Chol, as a component of lipoplexes with [DOPE], has been used for siRNA delivery and gene silencing in MCF-7 cells and in mice via intravenous injection, resulting in lipoplex accumulation in the liver. Additionally, it has been employed in cationic nanoparticles with [Tween 80] to transfect pDNA and siRNA into PC3 mouse xenografts via intratumoral injection and with [Tween 80] and [folate-PEG2000-DSPE] in a KB mouse xenograft model for intratumoral gene delivery.

CAY10701 is a 7-deazahypoxanthine analog that prevents microtubule formation, blocking the proliferation of HeLa and MCF-7 cells (GI50s = 22 and 38 nM, respectively). It also inhibits the growth of several different colorectal cancer cell lines (GI50 values range from 9 to 17 nM), while being at least 1,500-fold less effective against normal human fibroblast WI38 cells. CAY10701 is effective in vivo, reducing tumor volume in colorectal cell xenografts in mice without significantly altering body weight.

Lifirafenib, also known as Beigene-283, is a Novel potent and selective RAF Kinase and EGFR inhibitor. BGB-283-displays Potent Antitumor Activity in B-RAF Mutated Colorectal Cancers. In vitro, BGB-283 potently inhibits B-RAFV600E-activated ERK phosphorylation and cell proliferation. It demonstrates selective cytotoxicity and preferentially inhibits proliferation of cancer cells harbouring B-RAFV600E and EGFR mutation/amplification. In B-RAFV600E CRC cell lines, BGB-283 effectively inhibits the reactivation of EGFR and EGFR-mediated cell proliferation. In vivo, BGB-283 treatment leads to dose-dependent tumor growth inhibition accompanied by partial and complete tumor regressions in both cell-line derived and primary human colorectal tumor xenografts bearing B-RAFV600E mutation. BGB-283 as a potent antitumor drug candidate with clinical potential for treating CRC harbouring B-RAFV600E mutation.

Verubulin (MPC 6827) is a potent microtubule blocker with cytotoxic and potentially anticancer activity that disrupts newly formed blood vessels in xenografts, and can be used to image microtubules (MTs) using positron emission tomography (PET).

2′-Deoxy-4′-thiocytidine (T-dCyd), a novel epigenetic agent, markedly increases p21 levels upon administration. Additionally, this compound has demonstrated the ability to eradicate tumor cells in double-mutant xenografts [1].

TAK-960 hydrochloride is a potent, selective, orally active inhibitor of polo-like kinase 1 (PLK1) (IC50: 0.8 nM). TAK-960 hydrochloride inhibits the proliferation of a variety of tumour cell lines and significantly treats a variety of tumour xenografts.

NT113 is a pan-ERBB inhibitor with high brain penetrance. NT113 is active against GBM xenografts in which wild-type EGFR or EGFRvIII is highly expressed. NT113 inhibits the growth of glioblastoma xenografts with EGFR amplification. NT113 has inhibitory ac

CB 300919 is a quinazoline-based antitumor agent exhibiting high activity against CH1 human ovarian tumor xenografts, with continuous exposure (96 h) resulting in a growth inhibition (IC50: 2 nM).

HDAC-IN-53 is an orally active, selective inhibitor of HDAC1-3, with IC50 values of 47 nM, 125 nM, and 450 nM, respectively. It exhibits no inhibitory effects on class II HDACs (HDAC4, 5, 6, 7, 9; IC50 >10 μM). The compound induces caspase-dependent apoptosis and significantly hampers the growth of human tumor xenografts in nude mice and murine tumor growth in immune-competent mice with MC38 colon cancer [1].

1-Palmitoyl-2-hydroxy-sn-glycero-3-PE is a naturally occurring lysophospholipid that inhibits the growth of L. donovani promastigotes (GIC50 = 8 uM). Its serum levels are decreased in mouse models of alcohol-induced liver injury and hepatocellular carcinoma and in humans following an exercise regimen of 2.5 hours of running for three days. It has also been used as an internal standard for quantifying saturated lysophosphoethanolamines.