WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205761
Description: ABT-510 is synthetic peptide that mimics the anti-angiogenic activity of the endogenous protein thrombospondin-1 (TSP-1). ABT-510 inhibits the actions of several pro-angiogenic growth factors important to tumor neovascularization; these pro-angiogenic growth factors include vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF)), hepatocyte growth factor (HGF), and interleukin 8 (IL-8).
MedKoo Cat#: 205761
Chemical Formula: C46H83N13O11
Exact Mass: 993.6335
Molecular Weight: 994.23
Elemental Analysis: C, 55.57; H, 8.41; N, 18.31; O, 17.70
Synonym: ABT510; ABT 510; ABT-510
IUPAC/Chemical Name: (S)-1-((2S,5S,8S,11S,14R,17S)-5,14-di((S)-sec-butyl)-2-(3-guanidinopropyl)-11-((S)-1-hydroxyethyl)-17-isopropyl-24-methyl-4,7,10,13,16,19,22,25-octaoxo-8-propyl-3,6,9,12,15,18,21,24-octaazahexacosan-1-oyl)-N-ethylpyrrolidine-2-carboxamide
InChi Key: RIWLPSIAFBLILR-SYGZVSRYSA-N
InChi Code: InChI=1S/C46H83N13O11/c1-12-18-30(39(64)55-36(26(7)13-2)42(67)53-31(19-16-21-50-46(47)48)45(70)59-22-17-20-32(59)40(65)49-15-4)52-44(69)38(28(9)60)57-43(68)37(27(8)14-3)56-41(66)35(25(5)6)54-33(62)23-51-34(63)24-58(11)29(10)61/h25-28,30-32,35-38,60H,12-24H2,1-11H3,(H,49,65)(H,51,63)(H,52,69)(H,53,67)(H,54,62)(H,55,64)(H,56,66)(H,57,68)(H4,47,48,50)/t26-,27-,28-,30-,31-,32-,35-,36-,37+,38-/m0/s1
SMILES Code: O=C([C@H]1N(C([C@H](CCCNC(N)=N)NC([C@H]([C@@H](C)CC)NC([C@H](CCC)NC([C@H]([C@@H](O)C)NC([C@@H]([C@@H](C)CC)NC([C@H](C(C)C)NC(CNC(CN(C)C(C)=O)=O)=O)=O)=O)=O)=O)=O)=O)CCC1)NCC
ABT-510 is a subcutaneously (SC) administered nonapeptide thrombospondin analogue in phase 2 clinical development for treatment of advanced malignancies. ABT-510 was showing promise as an angiogenesis inhibitor or anti-angiogenic agent, meaning it works by stopping the growth of new blood vessels. This Thrombospondin 1 mimetic works through CD36 and has been shown to block angiogenesis in vitro and in vivo and to slow tumor growth in mice. ABT-510 was shown to be effective in both xenograft models and in a study of companion dogs with spontaneous tumors. Not only were objective responses observed after 60 days, but a decrease in levels of circulating endothelial cells was also found. In human studies, ABT-510 was found to be safe and have efficacy in phase I trials in combination regimens and as a single agent, where its use was associated with a decrease in bFGF levels and stable disease in six patients for at least six months. The combination of bevacizumab and ABT-510 has been shown (in a phase I study) to be effective in promoting stable disease in 44% of patients with advanced solid tumors. Unfortunately, the recent phase II study of ABT-510 for treatment of metastatic melanoma failed to reach its primary endpoint resulting in early termination of the study. Only three out of twenty-one patients reached the primary endpoint of progression-free survival at 18 weeks, but these three patients remained progression-free for 21, 34, and 42 weeks. However, biomarker data collected during this study showed a decrease in VEGF-C, circulating endothelial cells, and CD146 and CD34/133 counts, and a maximum tolerated dose has still not been established. Further study could consider a higher dose and/or combination treatment. (source: http://en.wikipedia.org/wiki/ABT-510).
1: Campbell NE, Greenaway J, Henkin J, Moorehead RA, Petrik J. The thrombospondin-1 mimetic ABT-510 increases the uptake and effectiveness of cisplatin and paclitaxel in a mouse model of epithelial ovarian cancer. Neoplasia. 2010 Mar;12(3):275-83. PubMed PMID: 20234821; PubMed Central PMCID: PMC2838444.
2: Nabors LB, Fiveash JB, Markert JM, Kekan MS, Gillespie GY, Huang Z, Johnson MJ, Meleth S, Kuo H, Gladson CL, Fathallah-Shaykh HM. A phase 1 trial of ABT-510 concurrent with standard chemoradiation for patients with newly diagnosed glioblastoma. Arch Neurol. 2010 Mar;67(3):313-9. PubMed PMID: 20212229.
3: Tolle JC, Becker CL, Califano JC, Chang JL, Gernhardt K, Napier JJ, Wittenberger SJ, Yuan J. Impurity rejection in the crystallization of ABT-510 as a method to establish starting material specifications. Adv Exp Med Biol. 2009;611:595-6. PubMed PMID: 19400326.
4: Becker CL, Califano JC, Tolle JC, Napier JJ, Kolaczkowski L, Chang SJ, Tian Z, Manna S. Evolution of the synthetic process to prepare the tripeptide segment of ABT-510. Adv Exp Med Biol. 2009;611:575-6. PubMed PMID: 19400320.
5: Hasina R, Martin LE, Kasza K, Jones CL, Jalil A, Lingen MW. ABT-510 is an effective chemopreventive agent in the mouse 4-nitroquinoline 1-oxide model of oral carcinogenesis. Cancer Prev Res (Phila). 2009 Apr;2(4):385-93. Epub 2009 Mar 31. PubMed PMID: 19336725; PubMed Central PMCID: PMC2702843.
6: Greenaway J, Henkin J, Lawler J, Moorehead R, Petrik J. ABT-510 induces tumor cell apoptosis and inhibits ovarian tumor growth in an orthotopic, syngeneic model of epithelial ovarian cancer. Mol Cancer Ther. 2009 Jan;8(1):64-74. PubMed PMID: 19139114.
7: Baker LH, Rowinsky EK, Mendelson D, Humerickhouse RA, Knight RA, Qian J, Carr RA, Gordon GB, Demetri GD. Randomized, phase II study of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 in patients with advanced soft tissue sarcoma. J Clin Oncol. 2008 Dec 1;26(34):5583-8. Epub 2008 Nov 3. PubMed PMID: 18981463.
8: Gordon MS, Mendelson D, Carr R, Knight RA, Humerickhouse RA, Iannone M, Stopeck AT. A phase 1 trial of 2 dose schedules of ABT-510, an antiangiogenic, thrombospondin-1-mimetic peptide, in patients with advanced cancer. Cancer. 2008 Dec 15;113(12):3420-9. PubMed PMID: 18932258.
9: Punekar S, Zak S, Kalter VG, Dobransky L, Punekar I, Lawler JW, Gutierrez LS. Thrombospondin 1 and its mimetic peptide ABT-510 decrease angiogenesis and inflammation in a murine model of inflammatory bowel disease. Pathobiology. 2008;75(1):9-21. Epub 2008 Mar 11. PubMed PMID: 18334835.
10: Isenberg JS, Yu C, Roberts DD. Differential effects of ABT-510 and a CD36-binding peptide derived from the type 1 repeats of thrombospondin-1 on fatty acid uptake, nitric oxide signaling, and caspase activation in vascular cells. Biochem Pharmacol. 2008 Feb 15;75(4):875-82. Epub 2007 Nov 1. PubMed PMID: 18068687; PubMed Central PMCID: PMC2267764.