129298-91-5 Usage
Description
AGM-1470, also known as TNP-470, is a synthetic analog of fumagillin, a natural product derived from Aspergillus fumigatus. It is an angiogenesis inhibitor that irreversibly inactivates methionine aminopeptidase-2 (MetAP2), blocking endothelial cell proliferation and angiogenesis. AGM-1470 has therapeutic potential in cancer and microsporidiosis treatment.
Uses
Used in Cancer Therapy:
AGM-1470 is used as an anti-cancer agent for its ability to inhibit angiogenesis, a process essential for tumor growth and metastasis. By targeting MetAP2, it can limit the proliferation of endothelial cells and disrupt the formation of new blood vessels that supply nutrients to the tumor.
Used in Microsporidiosis Treatment:
AGM-1470 is used as an anti-infective agent for the treatment of microsporidiosis, a disease caused by microsporidian parasites. Its anti-angiogenic properties also contribute to its therapeutic potential in this application.
Used in Drug Development:
As a synthetic analog of fumagillin, AGM-1470 is used in research and development for the creation of new drugs with improved anti-angiogenic and anti-infective properties. Its unique mechanism of action targeting MetAP2 makes it a valuable compound for studying and developing novel therapeutic agents.
Used in Angiogenesis Research:
AGM-1470 is used as a research tool to study the process of angiogenesis and its role in various diseases, including cancer and microsporidiosis. Its ability to irreversibly inactivate MetAP2 provides insights into the regulation of blood vessel formation and the potential for developing targeted therapies.
Biological Activity
Analog of Fumagillin ((2E,4E,6E,8E)-Mono[(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2 -methyl-3-(3-methyl-2-butenyl)oxiranyl]-1-oxaspiro[2.5] oct-6-yl] 2,4,6,8-decatetraenedioic acid ester) that displays potent antiangiogenic activity in vitro and in vivo . Inhibits methionine aminopeptidase type II (MetAP2).
Biochem/physiol Actions
TNP-470 is a methionine aminopeptidase-2 (MetAP-2) inhibitor, selective for MetAP-2 over MetAP11. TNP-470 is an antiangiogenic.
in vitro
antitumor activity of tnp-470 was evaluated in eight human cultured cell lines derived from choriocarcinoma; ovarian cancer; tyk and nakajima; and uterine endometrial cancer. results showed that after 7-day culture with tnp-470, in medium at the concentration of 10 to 10-2 μg/ml, the inhibition of growth was observed in all of the eight cell lines. the half inhibitory concentration of choriocarcinoma cell lines was at an extremely low level compared to that of e uterine endometrial cancer and pithelial ovarian cancer [1].
in vivo
the anti-tumor effect of tnp-470 was studied using nude mice with tumors of gch-1(m), nuc-1, or nakajima cells. when the size of the transplanted tumor reached 100–200 mm3, 3, 10, or 30 mg/kg of tnp-470 was injected every other day. it was found that the inhibitory effect of tnp-470 was obtained by the administration of 10 and 30 mg/kg in gch-1(m) and nuc-1 cells, respectively, while in nakajima cells there was no significant effect. in addition, in nude mice treated with 30 mg/kg of tnp-470, lung metastasis of gch-1(m) cells was greatly inhibited both in the number and the size of tumor nodules, suggesting that the capillary growth in the originally developed tumor was also reduced [1].
IC 50
2 μm
references
[1] t. yanase, m. tamura, k. rujita, et al. inhibitory effect of angiogenesis inhibitor tnp-470 on tumor growth and metastasis of human cell lines in vitro and in vivo. cancer research 53(11), 2566-2570 (1993). [2] c j logothetis et al. phase i trial of the angiogenesis inhibitor tnp-470 for progressive androgen-independent prostate cancer. clinical cancer research 7(5):1198-203.
Check Digit Verification of cas no
The CAS Registry Mumber 129298-91-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,2,9,2,9 and 8 respectively; the second part has 2 digits, 9 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 129298-91:
(8*1)+(7*2)+(6*9)+(5*2)+(4*9)+(3*8)+(2*9)+(1*1)=165
165 % 10 = 5
So 129298-91-5 is a valid CAS Registry Number.
InChI:InChI=1/C19H28ClNO6/c1-11(2)5-6-13-18(3,27-13)16-15(24-4)12(7-8-19(16)10-25-19)26-17(23)21-14(22)9-20/h5,12-13,15-16H,6-10H2,1-4H3,(H,21,22,23)/t12-,13-,15-,16-,18+,19+/m1/s1
129298-91-5Relevant articles and documents
Chemical modification of fumagillin. I. 6-O-Acyl, 6-O-sulfonyl, 6-O-alkyl, and 6-O-(N-substituted-carbamoyl)fumagillols
Marui,Itoh,Kozai,Sudo,Kishimoto
, p. 96 - 101 (2007/10/02)
The hydroxy group of fumagillol (3), a degradation product of fumagillin (1), was acylated, sulfonylated, alkylated or carbamoylated, and the anti-angiogenic activity of the resulting products was examined. These compounds inhibited the angiogenesis induced by basic fibroblast growth factor in the rat corneal micropocket assay and the growth of vascular endothelial cells in vitro. Among them, compound 2 (AGM-1470) was found to show the most potent inhibitory effect on the growth of vascular endothelial cells and was selected from this series as a candidate for further development.
