PI-103
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 202235

CAS#: 371935-74-9 (free base)

Description: PI-103 is a potent, cell-permeable, ATP-competitive inhibitor of phosphatidylinositol 3-kinase (PI3K) family members with selectivity toward DNA-PK, PI3K (p110α), and mTOR.


Price and Availability

Size
Price

100mg
USD 850
1g
USD 3450
Size
Price

200mg
USD 1450
2g
USD 4450
Size
Price

500mg
USD 2150
5g
USD 6550

PI-103, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 202235
Name: PI-103
CAS#: 371935-74-9 (free base)
Chemical Formula: C19H17ClN4O3
Exact Mass: 384.09892
Molecular Weight: 384.81628
Elemental Analysis: C, 59.30; H, 4.45; Cl, 9.21; N, 14.56; O, 12.47


Synonym: PI103; PI-103; PI 103.

IUPAC/Chemical Name: 3-(4-morpholinopyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl)phenol

InChi Key: TUVCWJQQGGETHL-UHFFFAOYSA-N

InChi Code: InChI=1S/C19H16N4O3/c24-13-4-1-3-12(11-13)17-21-15-14-5-2-6-20-19(14)26-16(15)18(22-17)23-7-9-25-10-8-23/h1-6,11,24H,7-10H2

SMILES Code: OC1=CC=CC(C2=NC(N3CCOCC3)=C(OC4=NC=CC=C45)C5=N2)=C1


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

Related CAS#
371935-74-9 (free base);
371935-79-4 (HCl)
 
 


References

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2: Moreira-Leite FF, Harrison LR, Mironov A, Roberts RA, Dive C. Inducible EGFR T790M-mediated gefitinib resistance in non-small cell lung cancer cells does not modulate sensitivity to PI103 provoked autophagy. J Thorac Oncol. 2010 Jun;5(6):765-77. PubMed PMID: 20421816.

3: Ding Z, Liang J, Li J, Lu Y, Ariyaratna V, Lu Z, Davies MA, Westwick JK, Mills GB. Physical association of PDK1 with AKT1 is sufficient for pathway activation independent of membrane localization and phosphatidylinositol 3 kinase. PLoS One. 2010 Mar 26;5(3):e9910. PubMed PMID: 20361045; PubMed Central PMCID: PMC2845649.

4: Miller S, Tavshanjian B, Oleksy A, Perisic O, Houseman BT, Shokat KM, Williams RL. Shaping development of autophagy inhibitors with the structure of the lipid kinase Vps34. Science. 2010 Mar 26;327(5973):1638-42. PubMed PMID: 20339072; PubMed Central PMCID: PMC2860105.

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6: Sos ML, Rode HB, Heynck S, Peifer M, Fischer F, Klüter S, Pawar VG, Reuter C, Heuckmann JM, Weiss J, Ruddigkeit L, Rabiller M, Koker M, Simard JR, Getlik M, Yuza Y, Chen TH, Greulich H, Thomas RK, Rauh D. Chemogenomic profiling provides insights into the limited activity of irreversible EGFR Inhibitors in tumor cells expressing the T790M EGFR resistance mutation. Cancer Res. 2010 Feb 1;70(3):868-74. Epub 2010 Jan 26. PubMed PMID: 20103621.

7: Janes MR, Limon JJ, So L, Chen J, Lim RJ, Chavez MA, Vu C, Lilly MB, Mallya S, Ong ST, Konopleva M, Martin MB, Ren P, Liu Y, Rommel C, Fruman DA. Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor. Nat Med. 2010 Feb;16(2):205-13. Epub 2010 Jan 13. PubMed PMID: 20072130.

8: No M, Choi EJ, Kim IA. Targeting HER2 signaling pathway for radiosensitization: alternative strategy for therapeutic resistance. Cancer Biol Ther. 2009 Dec;8(24):2351-61. Epub 2009 Dec 19. PubMed PMID: 19923913.

9: López-Fauqued M, Gil R, Grueso J, Hernandez-Losa J, Pujol A, Moliné T, Recio JA. The dual PI3K/mTOR inhibitor PI-103 promotes immunosuppression, in vivo tumor growth and increases survival of sorafenib-treated melanoma cells. Int J Cancer. 2010 Apr 1;126(7):1549-61. PubMed PMID: 19810100.

10: Link W, Oyarzabal J, Serelde BG, Albarran MI, Rabal O, Cebriá A, Alfonso P, Fominaya J, Renner O, Peregrina S, Soilán D, Ceballos PA, Hernández AI, Lorenzo M, Pevarello P, Granda TG, Kurz G, Carnero A, Bischoff JR. Chemical interrogation of FOXO3a nuclear translocation identifies potent and selective inhibitors of phosphoinositide 3-kinases. J Biol Chem. 2009 Oct 9;284(41):28392-400. Epub 2009 Aug 18. PubMed PMID: 19690175; PubMed Central PMCID: PMC2788888.

11: Westhoff MA, Kandenwein JA, Karl S, Vellanki SH, Braun V, Eramo A, Antoniadis G, Debatin KM, Fulda S. The pyridinylfuranopyrimidine inhibitor, PI-103, chemosensitizes glioblastoma cells for apoptosis by inhibiting DNA repair. Oncogene. 2009 Oct 8;28(40):3586-96. Epub 2009 Jul 27. PubMed PMID: 19633683.

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13: 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. 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 Ther. 2009 Jul;8(7):1725-38. Epub 2009 Jul 7. PubMed PMID: 19584227; PubMed Central PMCID: PMC2718129.

14: Schwab J, Antonescu C, Boland P, Healey J, Rosenberg A, Nielsen P, Iafrate J, Delaney T, Yoon S, Choy E, Harmon D, Raskin K, Yang C, Mankin H, Springfield D, Hornicek F, Duan Z. Combination of PI3K/mTOR inhibition demonstrates efficacy in human chordoma. Anticancer Res. 2009 Jun;29(6):1867-71. PubMed PMID: 19528441.

15: Zou ZQ, Zhang XH, Wang F, Shen QJ, Xu J, Zhang LN, Xing WH, Zhuo RJ, Li D. A novel dual PI3Kalpha/mTOR inhibitor PI-103 with high antitumor activity in non-small cell lung cancer cells. Int J Mol Med. 2009 Jul;24(1):97-101. PubMed PMID: 19513541.

16: Zou CY, Smith KD, Zhu QS, Liu J, McCutcheon IE, Slopis JM, Meric-Bernstam F, Peng Z, Bornmann WG, Mills GB, Lazar AJ, Pollock RE, Lev D. Dual targeting of AKT and mammalian target of rapamycin: A potential therapeutic approach for malignant peripheral nerve sheath tumor. Mol Cancer Ther. 2009 May 5. [Epub ahead of print] PubMed PMID: 19417153.

17: Ebi H, Tomida S, Takeuchi T, Arima C, Sato T, Mitsudomi T, Yatabe Y, Osada H, Takahashi T. Relationship of deregulated signaling converging onto mTOR with prognosis and classification of lung adenocarcinoma shown by two independent in silico analyses. Cancer Res. 2009 May 1;69(9):4027-35. Epub 2009 Apr 21. PubMed PMID: 19383916.

18: Hancock MK, Kopp L, Bi K. High-throughput screening compatible cell-based assay for interrogating activated notch signaling. Assay Drug Dev Technol. 2009 Feb;7(1):68-79. PubMed PMID: 19382889.

19: Chiarini F, Falà F, Tazzari PL, Ricci F, Astolfi A, Pession A, Pagliaro P, McCubrey JA, Martelli AM. Dual inhibition of class IA phosphatidylinositol 3-kinase and mammalian target of rapamycin as a new therapeutic option for T-cell acute lymphoblastic leukemia. Cancer Res. 2009 Apr 15;69(8):3520-8. Epub 2009 Apr 7. PubMed PMID: 19351820.

20: Niedermeier M, Hennessy BT, Knight ZA, Henneberg M, Hu J, Kurtova AV, Wierda WG, Keating MJ, Shokat KM, Burger JA. Isoform-selective phosphoinositide 3'-kinase inhibitors inhibit CXCR4 signaling and overcome stromal cell-mediated drug resistance in chronic lymphocytic leukemia: a novel therapeutic approach. Blood. 2009 May 28;113(22):5549-57. Epub 2009 Mar 24. PubMed PMID: 19318683.

21: Markadieu N, Crutzen R, Boom A, Erneux C, Beauwens R. Inhibition of insulin-stimulated hydrogen peroxide production prevents stimulation of sodium transport in A6 cell monolayers. Am J Physiol Renal Physiol. 2009 Jun;296(6):F1428-38. Epub 2009 Mar 18. PubMed PMID: 19297450.

22: Chaussade C, Cho K, Mawson C, Rewcastle GW, Shepherd PR. Functional differences between two classes of oncogenic mutation in the PIK3CA gene. Biochem Biophys Res Commun. 2009 Apr 17;381(4):577-81. Epub 2009 Feb 20. PubMed PMID: 19233141.

23: Kong D, Yaguchi S, Yamori T. Effect of ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor, on DNA-dependent protein kinase. Biol Pharm Bull. 2009 Feb;32(2):297-300. PubMed PMID: 19182393.

24: Guillard S, Clarke PA, Te Poele R, Mohri Z, Bjerke L, Valenti M, Raynaud F, Eccles SA, Workman P. Molecular pharmacology of phosphatidylinositol 3-kinase inhibition in human glioma. Cell Cycle. 2009 Feb 1;8(3):443-53. Epub 2009 Feb 16. PubMed PMID: 19177002.

25: Zhang TT, Okkenhaug K, Nashed BF, Puri KD, Knight ZA, Shokat KM, Vanhaesebroeck B, Marshall AJ. Genetic or pharmaceutical blockade of p110delta phosphoinositide 3-kinase enhances IgE production. J Allergy Clin Immunol. 2008 Oct;122(4):811-819.e2. PubMed PMID: 19014771.

26: Chaisuparat R, Hu J, Jham BC, Knight ZA, Shokat KM, Montaner S. Dual inhibition of PI3Kalpha and mTOR as an alternative treatment for Kaposi's sarcoma. Cancer Res. 2008 Oct 15;68(20):8361-8. PubMed PMID: 18922908; PubMed Central PMCID: PMC2645787.

27: Degtyarev M, De Mazière A, Orr C, Lin J, Lee BB, Tien JY, Prior WW, van Dijk S, Wu H, Gray DC, Davis DP, Stern HM, Murray LJ, Hoeflich KP, Klumperman J, Friedman LS, Lin K. Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents. J Cell Biol. 2008 Oct 6;183(1):101-16. PubMed PMID: 18838554; PubMed Central PMCID: PMC2557046.

28: Zanella F, Rosado A, García B, Carnero A, Link W. Chemical genetic analysis of FOXO nuclear-cytoplasmic shuttling by using image-based cell screening. Chembiochem. 2008 Sep 22;9(14):2229-37. PubMed PMID: 18756565.

29: Kharas MG, Janes MR, Scarfone VM, Lilly MB, Knight ZA, Shokat KM, Fruman DA. Ablation of PI3K blocks BCR-ABL leukemogenesis in mice, and a dual PI3K/mTOR inhibitor prevents expansion of human BCR-ABL+ leukemia cells. J Clin Invest. 2008 Sep;118(9):3038-50. PubMed PMID: 18704194; PubMed Central PMCID: PMC2515380.

30: Prevo R, Deutsch E, Sampson O, Diplexcito J, Cengel K, Harper J, O'Neill P, McKenna WG, Patel S, Bernhard EJ. Class I PI3 kinase inhibition by the pyridinylfuranopyrimidine inhibitor PI-103 enhances tumor radiosensitivity. Cancer Res. 2008 Jul 15;68(14):5915-23. PubMed PMID: 18632646.

31: Park S, Chapuis N, Bardet V, Tamburini J, Gallay N, Willems L, Knight ZA, Shokat KM, Azar N, Viguié F, Ifrah N, Dreyfus F, Mayeux P, Lacombe C, Bouscary D. PI-103, a dual inhibitor of Class IA phosphatidylinositide 3-kinase and mTOR, has antileukemic activity in AML. Leukemia. 2008 Sep;22(9):1698-706. Epub 2008 Jun 12. PubMed PMID: 18548104.

32: Kojima K, Shimanuki M, Shikami M, Samudio IJ, Ruvolo V, Corn P, Hanaoka N, Konopleva M, Andreeff M, Nakakuma H. The dual PI3 kinase/mTOR inhibitor PI-103 prevents p53 induction by Mdm2 inhibition but enhances p53-mediated mitochondrial apoptosis in p53 wild-type AML. Leukemia. 2008 Sep;22(9):1728-36. Epub 2008 Jun 12. PubMed PMID: 18548093.

33: Biswas SK, Zhao Y, Nagalingam A, Gardner TW, Sandirasegarane L. PDGF- and insulin/IGF-1-specific distinct modes of class IA PI 3-kinase activation in normal rat retinas and RGC-5 retinal ganglion cells. Invest Ophthalmol Vis Sci. 2008 Aug;49(8):3687-98. Epub 2008 Apr 17. PubMed PMID: 18421086.

34: Chen JS, Zhou LJ, Entin-Meer M, Yang X, Donker M, Knight ZA, Weiss W, Shokat KM, Haas-Kogan D, Stokoe D. Characterization of structurally distinct, isoform-selective phosphoinositide 3'-kinase inhibitors in combination with radiation in the treatment of glioblastoma. Mol Cancer Ther. 2008 Apr;7(4):841-50. PubMed PMID: 18413797.

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37: Fan QW, Cheng CK, Nicolaides TP, Hackett CS, Knight ZA, Shokat KM, Weiss WA. A dual phosphoinositide-3-kinase alpha/mTOR inhibitor cooperates with blockade of epidermal growth factor receptor in PTEN-mutant glioma. Cancer Res. 2007 Sep 1;67(17):7960-5. PubMed PMID: 17804702; PubMed Central PMCID: PMC2597547.

38: Raynaud FI, Eccles S, Clarke PA, Hayes A, Nutley B, Alix S, Henley A, Di-Stefano F, Ahmad Z, Guillard S, Bjerke LM, Kelland L, Valenti M, Patterson L, Gowan S, de Haven Brandon A, Hayakawa M, Kaizawa H, Koizumi T, Ohishi T, Patel S, Saghir N, Parker P, Waterfield M, Workman P. Pharmacologic characterization of a potent inhibitor of class I phosphatidylinositide 3-kinases. Cancer Res. 2007 Jun 15;67(12):5840-50. PubMed PMID: 17575152.

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