Tìm theo
PPI-2458
Thuốc Gốc
Small Molecule
CTHH: C22H36N2O6
PTK: 424.531
PPI-2458 represents a potentially new and important addition to the growing list of therapeutics aimed at specific molecular oncology targets. PPI-2458 is a novel, proprietary molecule belonging to the fumagillin class of compounds that specifically targets the MetAP-2 enzyme. This class of compounds has been shown to prevent both abnormal cell growth and the formation of new blood vessels (known as angiogenesis), which contribute to the growth of aberrant tissues in diseases such as cancer and rheumatoid arthritis. Clinical development with previous fumagillin derivatives has been limited by their toxicity profile. In preclinical studies to date, PPI-2458 has demonstrated the potent pharmacologic activity of this class of compounds while displaying an improved pharmacokinetic and toxicity profile.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C22H36N2O6
Phân tử khối
424.531
Monoisotopic mass
424.257336894
InChI
InChI=1S/C22H36N2O6/c1-12(2)7-8-15-21(5,30-15)18-17(27-6)14(9-10-22(18)11-28-22)29-20(26)24-16(13(3)4)19(23)25/h7,13-18H,8-11H2,1-6H3,(H2,23,25)(H,24,26)/t14-,15-,16-,17-,18-,21+,22+/m1/s1
InChI Key
InChIKey=QBDVVYNLLXGUGN-XGTBZJOHSA-N
IUPAC Name
(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl N-[(1R)-1-carbamoyl-2-methylpropyl]carbamate
Traditional IUPAC Name
(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl N-[(1R)-1-carbamoyl-2-methylpropyl]carbamate
SMILES
[H][C@@]1([C@H](OC)[C@@H](CC[C@]11CO1)OC(=O)N[C@H](C(C)C)C(N)=O)[C@@]1(C)O[C@@H]1CC=C(C)C
Độ hòa tan
4.39e-02 g/l
logP
2.07
logS
-4
pKa (strongest acidic)
13.45
pKa (Strongest Basic)
-3.6
PSA
115.71 Å2
Refractivity
110.43 m3·mol-1
Polarizability
46.28 Å3
Rotatable Bond Count
9
H Bond Acceptor Count
5
H Bond Donor Count
2
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
Cơ Chế Tác Dụng : PPI-2458 represents a potentially new and important addition to the growing list of therapeutics aimed at specific molecular oncology targets. PPI-2458 is a novel, proprietary molecule belonging to the fumagillin class of compounds that specifically targets the MetAP-2 enzyme. This class of compounds has been shown to prevent both abnormal cell growth and the formation of new blood vessels (known as angiogenesis), which contribute to the growth of aberrant tissues in diseases such as cancer and rheumatoid arthritis. Clinical development with previous fumagillin derivatives has been limited by their toxicity profile. In preclinical studies to date, PPI-2458 has demonstrated the potent pharmacologic activity of this class of compounds while displaying an improved pharmacokinetic and toxicity profile. PPI-2458's potent inhibition of MetAP-2 presents the potential for use as a new therapy for non-Hodgkin's lymphoma (NHL). MetAP-2 is highly expressed in human germinal center B cells. The neoplastic counterparts of these cells are the cell types observed in certain NHL subtypes, such as diffuse large B cell lymphoma and follicular lymphoma. PPI-2458 has been shown to reduce the formation of germinal centers in lymphoid tissues in vivo, have direct anti-proliferative activity on NHL cells in vitro and inhibit the growth of NHL tumors in a preclinical model in vivo. The anti-tumor activity of PPI-2458 was dose-dependent in this preclinical in vivo model and directly correlated with the level of molecular target MetAP-2 enzyme inhibition in tumor tissue, as measured by a proprietary, pharmacodynamic assay developed by PRAECIS. Additionally, the activity of PPI-2458 in this preclinical model was synergistic with several chemotherapeutic agents that are routinely used in combination in NHL patients.
Chỉ Định : Investigated for use/treatment in lymphoma (non-hodgkin's) and solid tumors.
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB05864
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=6918653
ChemSpider
http://www.chemspider.com/Chemical-Structure.5293846.html
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