Preclinical pharmacokinetics of the novel PI3K inhibitor GDC-0941 and prediction of its pharmacokinetics and efficacy in human

Xenobiotica

Volumn 41, Issue 12, 2011, Pages 1088-1099

  Salphati, Laurent ^a   Pang, Jodie ^a   Plise, Emile G ^a   Chou, Bilin ^a   Halladay, Jason S ^a   Olivero, Alan G ^a   Rudewicz, Patrick J ^a   Tian, Qingping ^a   Wong, Susan ^a   Zhang, Xiaolin ^a  

^a GENENTECH INC   (United States)

Author keywords

Allometric scaling; Human prediction; Pharmacokinetics; PI3K; PI3K inhibitor

Indexed keywords

2 (1H INDAZOL 4 YL) 6 (4 METHANESULFONYL 1 PIPERAZINYLMETHYL) 4 MORPHOLINOTHIENO[3,2 D]PYRIMIDINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER INHIBITION; CELL LINE; CELL PERMEABILIZATION; DOG; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG STRUCTURE; FEMALE; HAPLORHINI; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; PLASMA PROTEIN BINDING; WHOLE BODY AUTORADIOGRAPHY;

ADMINISTRATION, ORAL; ANIMALS; AREA UNDER CURVE; AUTORADIOGRAPHY; CARBON RADIOISOTOPES; CELL LINE; CELL MEMBRANE PERMEABILITY; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG EVALUATION, PRECLINICAL; FEMALE; HUMANS; INDAZOLES; MALE; MICROSOMES, LIVER; PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN KINASE INHIBITORS; SPECIES SPECIFICITY; SULFONAMIDES; TREATMENT OUTCOME; XENOGRAFT MODEL ANTITUMOR ASSAYS;

CANIS FAMILIARIS; MACACA FASCICULARIS; RATTUS;

EID: 80655128406     PISSN: 00498254     EISSN: 13665928     Source Type: Journal    
DOI: 10.3109/00498254.2011.603386     Document Type: Article

References (21)

1. Boxenbaum H. (1982). Interspecies scaling, allometry, physiological time, and the ground plan of pharmacokinetics. J Pharmacokinet Biopharm 10:201-227. (Pubitemid 12044187)
2. Chalhoub N, Baker SJ. (2009). PTEN and the PI3-kinase pathway in cancer. Annu Rev Pathol 4:127-150.
3. Davies B, Morris T. (1993). Physiological parameters in laboratory animals and humans. Pharm Res 10:1093-1095. (Pubitemid 23211439)
4. Engelman JA. (2009). Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer 9:550-562.
5. Engelman JA, Luo J, Cantley LC. (2006). Te evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 7:606-619. (Pubitemid 44100518)
6. Folkes AJ, Ahmadi K, Alderton WK, Alix S, Baker SJ, Box G, Chuckowree IS, Clarke PA, Depledge P, Eccles SA, Friedman LS, Hayes A, Hancox TC, Kugendradas A, Lensun L, Moore P, Olivero AG, Pang J, Patel S, Pergl-Wilson GH, Raynaud FI, Robson A, Saghir N, Salphati L, Sohal S, Ultsch MH, Valenti M, Wallweber HJ, Wan NC, Wiesmann C, Workman P, Zhyvoloup A, Zvelebil MJ, Shuttleworth SJ. (2008). Te identifcation of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1- ylmethyl)-4-morpholin-4-yl-thieno[3,2-d] pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer. J Med Chem 51:5522-5532.
7. Ghigo A, Hirsch E. (2008). Isoform selective phosphoinositide 3-kinase gamma and delta inhibitors and their therapeutic potential. Recent Pat Infamm Allergy Drug Discov 2:1-10. (Pubitemid 351524318)
8. Gibaldi M, Perrier D. (1982). Pharmacokinetics. New York: Marcel Dekker.
9. Gibbs JP.(2010). Prediction of exposure-response relationships to support frst-in-human study design. AAPS J 12:750-758.
10. Liu P, Cheng H, Roberts TM, Zhao JJ. (2009). Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 8:627-644.
11. Luo J, Manning BD, Cantley LC. (2003). Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell 4:257-262. (Pubitemid 37329790)
12. Mahmood I, Balian JD. (1996). Interspecies scaling: predicting clearance of drugs in humans. Tree diferent approaches. Xenobiotica 26:887-895. (Pubitemid 26343083)
13. Maira SM, Staufer F, Brueggen J, Furet P, Schnell C, Fritsch C, Brachmann S, Chène P, De Pover A, Schoemaker K, Fabbro D, Gabriel D, Simonen M, Murphy L, Finan P, Sellers W, García-Echeverría C. (2008). Identifcation and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ter 7:1851-1863.
14. Obach RS, Baxter JG, Liston TE, Silber BM, Jones BC, MacIntyre F, Rance DJ, Wastall P. (1997). Te prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data. J Pharmacol Exp Ter 283:46-58. (Pubitemid 27438945)
15. Raynaud FI, Eccles SA, Patel S, Alix S, Box G, Chuckowree I, Folkes A, Gowan S, De Haven Brandon A, Di Stefano F, Hayes A, Henley AT, Lensun L, Pergl-Wilson G, Robson A, Saghir N, Zhyvoloup A, McDonald E, Sheldrake P, Shuttleworth S, Valenti M, Wan NC, Clarke PA, Workman P. (2009). Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941. Mol Cancer Ter 8:1725-1738.
16. Salphati L, Lee LB, Pang J, Plise EG, Zhang X.(2010 a). Role of P-glycoprotein and breast cancer resistance protein-1 in the brain penetration and brain pharmacodynamic activity of the novel phosphatidylinositol 3-kinase inhibitor GDC-0941. Drug Metab Dispos 38:1422-1426.
17. Salphati L, Wong H, Belvin M, Bradford D, Edgar KA, Prior WW, Sampath D, Wallin JJ.(2010 b). Pharmacokinetic-pharmacodynamic modeling of tumor growth inhibition and biomarker modulation by the novel phosphatidylinositol 3-kinase inhibitor GDC-0941. Drug Metab Dispos 38:1436-1442.
18. Sarker D, Kristeleit R, Mazina KE, Ware JA, Yan Y, Dresser M, Derynck MA, de Bono JS. (2009). A phase I study evaluating the pharmacokinetics (PK) and pharmacodynamics (PD) of the oral pan-phosphoinositide-3 kinase (PI3K) inhibitor GDC-0941. J Clin Oncol 27, suppl; abstract 3538.
19. Seipelt I, Gerlach M, Baasner S, Blumenstein L, Schmidt P, Mueller G, Aicher B, Engel J, Guenther E, Teifel M.(2010). AEZS-132, a new orally bioavailable PI3K/Erk inhibitor with antitumor efects. Eur J Cancer 8, suppl; abstract 197.
20. Shapiro G, Molina J, Bendell J, Brana I, Spicer J, Kwak E, Pandya S, Milham R, Houk B, Bell-McGuinn K.(2010). First-in-human study of PF-05212384, a small molecule intravenous dual inhibitor of PI3K and mTOR in patients with advanced cancer: preliminary report on safety and pharmacokinetics. Eur J Cancer 8, suppl; abstract 387.
21. Wong KK, Engelman JA, Cantley LC.(2010). Targeting the PI3K signaling pathway in cancer. Curr Opin Genet Dev 20:87-90.