ONT-093: Ontogen

Current Opinion in Investigational Drugs

Volumn 3, Issue 11, 2002, Pages 1666-1671

  Mistry, Prakash ^a   Folkes, Adrian ^a  

^a Cantab Pharmaceuticals Ltd   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; ANTISENSE OLIGONUCLEOTIDE; AZIDOPINE; BIRICODAR; CYCLOSPORIN A; CYCLOSPORIN A DERIVATIVE; CYTOTOXIC AGENT; DOCETAXEL; DOXORUBICIN; ELACRIDAR; GLYCOPROTEIN P PUMP INHIBITOR; GW 120918; IMIDAZOLE DERIVATIVE; LOPERAMIDE; ONT 093; PACLITAXEL; PLACEBO; TARIQUIDAR; UNCLASSIFIED DRUG; VALSPODAR; VERAPAMIL; VINBLASTINE; ZOSUQUIDAR;

ANTINEOPLASTIC ACTIVITY; ATAXIA; CANCER CHEMOTHERAPY; CLINICAL TRIAL; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DELIVERY SYSTEM; DRUG DOSAGE FORM; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG MEGADOSE; DRUG METABOLISM; DRUG PENETRATION; DRUG POTENCY; DRUG POTENTIATION; DRUG STRUCTURE; DRUG TOXICITY; FOOD DRUG INTERACTION; HUMAN; MALIGNANT NEOPLASTIC DISEASE; MULTIDRUG RESISTANCE; NAUSEA AND VOMITING; NONHUMAN; REVIEW; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; THROMBOPHLEBITIS;

ANIMALS; CLINICAL TRIALS; DRUG RESISTANCE, MULTIPLE; HUMANS; IMIDAZOLES; NEOPLASMS; TECHNOLOGY, PHARMACEUTICAL;

EID: 0036881892     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (31)

1. 178728 A phase I trial of etoposide with the oral cyclosporin SDZ PSC 833, a modulator of multidrug resistance (MDR). Hausdorff J, Fisher GA, Halsey J, Collins HL, Lum BL, Brophy NA, Duran GE, Nix D, Pearce T, Sikic BI Proc Am Soc Clin Oncol 1995 14 Abs 407
2. 196036 Decreased mutation rate for cellular resistance to doxorubicin and suppression of mdr1 gene activation by the cyclosporin PSC 833. Beketic-Oreskovic L, Duran GE, Chen G, Dumontet C, Sikic BI J Natl Cancer Inst 1995 87 21 1593-1602
3. 282284 Ontogen Corporation announces issuance of US patent on new modulator for restoring sensitivity to multi-drug resistant tumor cells. Ontogen Corp Press Release 1998 March 26
4. 290265 Ontogen Corporation receives US patent covering modulators of multi-drug resistance. Ontogen Corp Press Release 1998 June 25
5. 311679 Reversal of P-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, LY335979. Dantzig AH, Shepard RL, Cao J, Law KL, Ehlhardt WJ, Baughman TM, Bumol TF, Starling JJ Cancer Res 1996 56 18 4171-4179
6. 313258 Ontogen Corporation announces completion of phase I study of multidrug resistance compound. Ontogen Corp Press Release 1999 Feb 03
7. 334333 Ontogen Corp completes phase I oral bioavailability study of multidrug resistance compound. Ontogen Corp Press Release 1999 July 29
8. 334730 Clinical trials of P-glycoprotein reversal in solid tumours. Ferry DR, Traunecker H, Kerr DJ Eur J Cancer 1996 32A 6 1070-1081
9. 347609 Ontogen Corp completes phase I multidose oral study of multidrug resistance compound OC144-093. Ontogen Corp Press Release 1999 November 15. Press release describing completion of a phase I multidose oral study with OC-144-093. Dr Ross Dixon (Executive Director) stated that 200 to 300 mg given twice a day may be a suitable dose schedule in combination with anticancer drugs and that OC-144-093 was being evaluated for its ability to enhance the oral bioavailability of drugs such as paclitaxel and saquinavir.
10. 360364 Rapid activation of MDR1 gene expression in human metastatic sarcoma after in vivo exposure to doxorubicin. Abolhoda A, Wilson AE, Ross H, Danenberg PV, Burt M, Scotto KW Clin Cancer Res 1999 5 11 3352-3356
11. 365622 Discovery 2000: Emerging strategies for drug discovery (Part II), San Diego, CA, USA. IDDB Meeting Report April 10-13
12. 373061 Discovery and characterization of OC144-093, a novel inhibitor of P-glycoprotein mediated multidrug resistance. Newman MJ, Rodarte JC, Benbatoul KD, Romano SJ, Zhang C, Krane S, Moran EJ, Uyeda RT, Dixon R, Guns ES, Mayer LD Cancer Res 2000 60 11 2964-2972 This report describes the in vitro characteristics of ONT-093, detailing potency in MDR cancer cells and interaction with P-gp. It also describes in vivo efficacy andn pharmacokinetics of the modulator.
13. 375431 CPT 2000 (Part IV) Seventh conference on clinical pharmacology and therapeutics and fourth congress of the European association for clinical pharmacology and therapeutics, Florence, Italy. Archibald K IDDB Meeting Report 2000 July 15-20
14. 376871 P-glycoprotein inhibitor OC144-093: Phase I oral safety and pharmacokinetics of a novel multidrhg resistance model. Lujan M, Lopez M, Guarjardo R, Dixon R, Toyonaga B Br J Clin Pharmacol 2000 July 15-20 Abs 967. This report describes and bioavailability and safety following a single 400 mg dose of ONT-093.
15. 390653 2,4,5-Trisubstituted imidazoles: Novel nontoxic modulators of P-glycoprotein mediated multidrug resistance. Part 1. Sarshar S, Zhang C, Moran EJ, Krane S, Rodarte JC, Benbatoul KD, Dixon R, Mjalli AMM Bioorg Med Chem Lett 2000 10 23 2599-2601. This report describes the synthesis, SAR and discovery of ONT-093.
16. 390656 2,4,5-Trisubstituted imidazoles: Novel nontoxic modulators of P-glycoprotein mediated multidrug resistance. Part 2. Zhang C, Sarshar S, Moran EJ, Krane S, Rodarte JC, Benbatoul KD, Dixon R, Mjalli AMM Bioorg Med Chem Lett 2000 10 23 2603-2605. This report describes the synthesis, SAR and discovery of ONT-093.
17. 401085 In vitro and in vivo reversal of P-glycoprotein mediated multidrug resistance by a novel potent modulator, XR-9576. Mistry P, Stewart AJ, Dangerfield W, Okiji S, Liddle C, Bootle D, Plumb JA, Templeton D, Charlton P Cancer Res 2001 61 2 749-758
18. 408109 Ontogen Corporation commences phase I study of OC144-093 as treatment for multidrug resistance in cancer therapy. Ontogen Corp Press Release 2001 May 03
19. 439751 Ontogen appoints Steven S Cowell to Board of Directors. Ontogen Corp Press Release 2002 February 13
20. 442263 Assessment of the involvement of CYP3A the vitro metabolism of a new modulator of MDR in cancer chemotherapy, OC144-193, by human liver microsomes. Guns ES, Bullock PL, Reimer ML, Dixon R, Bally M, Mayer LD Eur J Drug Metab Pharmacokinet 2001 26 2 273-282 This study shows that ONT-093 is not extensively metabolized by human liver microsomes, forming a single O-de-ethylated metabolite. It also describes the involvement of various cytochrome P450s in the metabolic process.
21. 442270 P-glycoprotein inhibitor OC144-093: Phase I intravenous and oral pharmacokinetics of a novel multidrug resistance modulator. Dixon R, Toyonaga B Proc Annu Meet Am Assoc Cancer Res 2000 41 Abs 3863 Report describes the pharmacokinetics and adverse effects of ONT-093 in phase I intravenous and oral dose trials.
22. 442279 Novel in vivo mechanism of action and lack of pharmacokinetic interaction with plasma paclitaxel by the P-glycoprotein inhibitor OC144-093. Newman MJ, Rodarte JC, Romano SJ, Ripka WC, Dixon R, Guns ES, Denyssevych T, Mayer LD. Proc Annu Meet Am Assoc Cancer Res 2000 41 398 This report indicates that ONT-093 can enhance antitumor efficacy of paclitaxel against breast carcinoma xenografts that do not express P-gp and that the modulator has no effects on the plasma pharmacokinetics of paclitaxel.
23. 446569 Enhancement of oral bioavailability of taxanes and CNS penetration of loperamide by the P-glycoprotein inhibitor OC144-093. Newman MJ, Lujan M, Silverman JA, Chan AO, Tran-Tau P, Toyonaga B, Dixon R Proc Annu Meet Am Assoc Cancer Res 2002 43 Abs 2140 Describes the enhancement of the oral bioavailability of paclitaxel and docetaxel and the enhancement of CNS penetration of loperamide by oral co-administration of ONT-093.
24. 457902 Ontogen - portfolio. Ontogen Corp. Company World Wide Web Site 2002 July 15
25. 461086 Pharmacologic approaches to reversing multidrug resistance. Sikic BI Semin Hematol 1997 34 Suppl 5 40-47
26. 465957 P-glycoprotein - A mediator of multidrug resistance in tumour cells. Germann UA Eur J Cancer 1996 32A 6 927-944
27. 465960 A phase I and pharmacokinetic study of bi-daily dosing of oral paclitaxel in combination with cyclosporin A. Malingre MM, Beijnen JH, Rosing H, Koopman FJ, Van Tellingen O, Duchin K, Ten Bokkel Huinink WW, Swart M, Lieverst J, Schellens JH Cancer Chemother Pharmacol 2001 47 4 347-354.
28. 465962 Increased oral bioavailability of paclitaxel by GF120918 in mice through selective modulation of P-glycoprotein. Bardelmeijer HA, Beijnen JH, Brouwer KR, Rosing H, Nooijen WJ, Van Tellingen O Clin Cancer Res 2000 6 4416-4421
29. 465973 Reversal of multidrug resistance by the P-glycoprotein modulator, LY335979, from the bench to the clinic. Dantzig AH, Law LK, Cao J, Starling JJ Curr Med Chem 2001 8 1 39-50
30. 466227 ONT-093: Reversing multidrug resistance (MDR) during chemotherapy. Ontogen Corp Company World Wide Web Site 2002 October 07
31. 466723 Overview: ABC transporters and human disease. Gottesman MM, Ambudkar SV J Bioenerg Biomembr 2001 33 6 453-458