p388

Etoposide (VP-16-213) is a topoisomerase II inhibitor that inhibits DNA synthesis by forming a complex with topoisomerase II and DNA (IC50=60.3 μM). Etoposide has antitumor activity and induces apoptosis and autophagy.

Erythromycin (E-Mycin) is a Macrolide and Macrolide Antimicrobial. The physiologic effect of erythromycin is by means of Decreased Sebaceous Gland Activity.

Indotecan (LMP-400) is an effective inhibitor of topoisomerase 1(Top1) (IC50: 300, 1200, 560 nM for P388, HCT116, MCF-7 cell lines, respectively).

N-acetyltyramine is a metabolite of the biogenic amine tyramine . It enhances cytotoxicity of doxorubicin in resistant P388 murine leukemia cells with an IC50 value of 0.13 μg/ml compared with an IC50 value of 0.48 μg/ml for doxorubicin alone.

Zosuquidar trihydrochloride (LY-335979 trihydrochloride) is a potent modulator of P-glycoprotein-mediated multi-drug resistance with Ki of 60 nM. Phase 3.

Sclareol, a labdane-type diterpene isolated from clary sage (Salvia sclarea), exerts growth inhibition and cytotoxic activity against a variety of human Y cell lines.

Nordihydroguaiaretic acid (NDGA) is a natural product, extracted from Pole Fork Kelaroa, and is a lipoxygenase (5-LOX) inhibitor (IC50=8 μM). Nordihydroguaiaretic acid possesses antioxidant and free radical scavenging properties.

Dihydrocytochalasin B (H2CB) is a cell division inhibitor that prevents cytokinesis, alters cell morphology, disrupts actin structures in Swiss/3T3 mouse fibroblasts, and inhibits DNA synthesis induced by serum growth factors in quiescent cultures. Low doses of H2CB lead to cell rounding and the loss of actin microfilament bundles.

Deoxylapachol has anti-wood rot activity, it can inhibit the brown rot fungi Gloeophyllum sepiarium CBS 353.74 and Gloeophyllum trabeum CBS 318.50 and the white rot fungi Merulius tremellosus CBS 280.73 and Phlebia brevispora CBS 509.92. It also can induc

BE-10988 is a DNA topoisomerase (DNAtopoisomerase) inhibitor. It suppresses the growth of P388 murine leukemia cell lines that are resistant to Doxorubicin and Vinblastine by promoting the formation of DNA topoisomerase complexes.

Sdz 280 446 is one of the most active cyclopeptolide of many resistance-modifying agents in restoring rhodamine-123 retention within multidrug-resistant P388 cells.

A 30312 is a fused indole, which overcomes multidrug resistance in P388/Adr cells in vitro. It potentiates the cytotoxicity of the antitumor drugs Adriamycin, vincristine and vinblastine in multidrug-resistant cells with no effect on drug-sensitive parent P388 cells.

PD 116152 is a highly substituted phenazine with antitumor activity isolated from the culture broth of a Streptomyces sp. The antitumor activity versus murine P388 leukemia is T/C 149. PD 116152 is selectively active versus the bacterium Streptococcus pne

MS-073 (CP-162398) is a P-glycoprotein inhibitor (P-gp). The in vitro resistance to vincristine (VCR) was almost completely reversed in VCR-resistant P388 cells, and the resistance of VCR, adriamycin (ADM), etoposide, and actinomycin D in ADM-resistant hu

Simetride is used in the Reversal of resistance to vincristine in P388 leukemia.

(+)-Goniothalesdiol, isolated from the bark of the Malaysian tree G. borneensis, is a tetrahydrofuran compound known to have significant cytotoxic effects against P388 mouse leukemia cells and pesticidal activities. It has been shown to have promising cytotoxic activity against p388 mouse leukemia cells (ED50 ≥30 μg/ml).

7-oxo Staurosporine is an antibiotic originally isolated from S. platensis with diverse biological activites. It inhibits PKC, PKA, phosphorylase kinase, EGFR, and c-Src in vitro (IC50s = 9, 26, 5, 200, and 800 nM, respectively). 7-oxo Staurosporine induces cell cycle arrest in the G2/M phase in human leukemia K562 cells with a minimal effective dose (MED) of 30 ng/ml. It is cytotoxic to P388 mouse leukemia cells that are resistant and susceptible to doxorubicin . 7-oxo Staurosporine inhibits growth of the mycelial, but not yeast form of C. albicans, C. krusei, C. tropicalis, and C. lusitaniae (MICs = 3.1-25 μg/ml). It increases sphingomyelin synthesis in CHO-K1 cells when used at a concentration of 50 nM.

(E)-5-(2-Bromovinyl)uracil (BVU) is a pyrimidine base and an inactive metabolite of the antiviral agents sorivudine and (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), which can be regenerated to BVDU in vivo. BVU irreversibly inactivates dihydropyrimidine dehydrogenase (DPD) in an NADPH-dependent manner, enhancing the efficacy of the chemotherapeutic agent and DPD substrate 5-fluorouracil in a P388 murine leukemia model when administered at a dose of 200 μmol/kg, thereby increasing survival time.

19,20-Epoxycytochalasin D is a fungal metabolite that has been found in the endophytic fungus Nemania sp. UM10M. It is active against the chloroquine-sensitive and -resistant strains of P. falciparum (MIC = 0.4 ng/ml for both) without inducing cytotoxicity in Vero cells. It is cytotoxic to BT-549, LLC-PK11, and P388 cells (IC50s = 7.84, 8.4, and 0.16 µM, respectively) but not SK-MEL, KB, or SKOV3 cells up to a concentration of 10 µM.

Migrastatin is a bacterial metabolite that has been found inStreptomyceswith antimuscarinic and anticancer activities.1,2It binds to M1-5muscarinic acetylcholine receptors (Kis = >200, 200, 31, 43, and >200 μM, respectively) and inhibits calcium mobilization induced by carbamoylcholine in SK-N-SH cells (IC50= 28 μM), as well as in primary rat bladder smooth muscle cells.1Migrastatin inhibits the migration of EC17 esophageal cancer cells in a wound healing assay (IC50= 10 μg/ml) and 4T1 mouse mammary carcinoma cells in a chamber cell migration assay (IC50= 29 μM).2It enhances cytotoxicity induced by vinblastine in vincristine-resistant P388/VCR cells.3

Thiocoraline is a depsipeptide and DNAbis-intercalator originally isolated fromMicromonosporawith antibacterial and anticancer activities.1,2It is active against the Gram-positive bacteriaS. aureus,B. subtilis, andM. luteus(MICs = 0.05, 0.05, and 0.03 μg/ml, respectively) but not Gram-negativeE. coli,K. pneumoniae, orP. aeruginosa(MICs = >100 μg/ml for all).1Thiocoraline inhibits RNA and DNA polymerase and thymidylate synthase (IC50s = 6, 6, and 15 μg/ml, respectively), as well as RNA and DNA synthesisin vitro(IC50s = 0.008 and 0.4 μg/ml, respectively). It is cytotoxic to P388, A549, HT-29, and MEL-28 cancer cells (IC50s = 0.002, 0.002, 0.01, and 0.002 μg/ml, respectively). 1.Romero, F., Espilego, F., Pérez Baz, J., et al.Thiocoraline, a new depsipeptide with antitumor activity produced by a marine Micromonospora. I. Taxonomy, fermentation, isolation, and biological activitiesJ. Antibiot. (Tokyo)50(9)734-737(1997) 2.Negri, A., Marco, E., García-Hernández, V., et al.Antitumor activity, X-ray crystal structure, and DNA binding properties of thiocoraline A, a natural bisintercalating thiodepsipeptideJ. Med. Chem.50(14)3322-3333(2007)

Quinaldopeptin is a quinomycin antibiotic. It is active against a variety of bacteria, including S. pyogenes, S. aureus, C. perfringens, S. faecalis, E. coli, and K. pneumoniae (MICs = 0.2, 0.4, 0.8, 1.6, 3.1 and 6.3 μg/ml, respectively). It is cytotoxic to B16/F10 and Moser cells (IC50s = 0.0008 and 0.04 μg/ml, respectively) and increases survival in a P388 leukemia mouse model. Quinaldopeptin is a bis-intercalator depsipeptide (NPBID) that binds to and intercalates into DNA (Kd = 32 nM).

Terrecyclic acid is a sesquiterpene originally isolated from A. terreus with antibiotic and anticancer activity. It is active against S. aureus, B. subtilis, and M. roseus (MICs = 25, 50, and 25 μg/ml, respectively). Terrecyclic acid induces a heat shock response, increases levels of reactive oxygen species (ROS), and inhibits NF-κB activity and cell growth in 3T3-Y9-B12 cells.

TAN 420E is a bacterial metabolite originally isolated from Streptomyces. It scavenges 2,2-diphenyl-1-picrylhydrazyl radicals in a cell-free assay (IC50 = 1.3 μM) and reduces thiobarbituric acid reactive substances (TBARS) in rat liver microsomes by 72% when used at a concentration of 100 μg/ml. TAN 420E is active against B. brevis, B. cereus, M. flavus, and S. aureus (MICs = 50-100 μg/ml). It is cytotoxic to P388 and KB lymphocytic leukemia cells (EC50s = 0.022 and 0.3 μg/ml, respectively).