BMS-754807
BMS-754807 is an orally bioavailable antagonist of human insulin-like growth factor type I receptor (IGF-1R) with potential antineoplastic activity. IGF-1R antagonist BMS-7548077 binds to IGF-1R, preventing IGF-1 ligand binding and activation of IGF-1R-mediated signaling pathways; inhibition of IGF-1R-mediated signaling pathways may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. IGF-1R is a receptor tyrosine kinase expressed on most tumor cells and is involved in mitogenesis, angiogenesis, and tumor cell survival.
1: Majo VJ, Arango V, Simpson NR, Prabhakaran J, Kassir SA, Underwood MD, Bakalian M, Canoll P, John Mann J, Dileep Kumar JS. Synthesis and in vitro evaluation of [18F]BMS-754807: a potential PET ligand for IGF-1R. Bioorg Med Chem Lett. 2013 Jul 15;23(14):4191-4. doi: 10.1016/j.bmcl.2013.05.026. Epub 2013 May 16. PubMed PMID: 23743281.
2: Awasthi N, Zhang C, Ruan W, Schwarz MA, Schwarz RE. BMS-754807, a small-molecule inhibitor of insulin-like growth factor-1 receptor/insulin receptor, enhances gemcitabine response in pancreatic cancer. Mol Cancer Ther. 2012 Dec;11(12):2644-53. doi: 10.1158/1535-7163.MCT-12-0447. Epub 2012 Oct 9. PubMed PMID: 23047891.
3: Lee SJ, Kim EJ, Lee HJ, Kim SY, Oh SJ, Ryu JS, Moon DH, Ahn JH, Kim SW. A pilot study for the early assessment of the effects of BMS-754807 plus gefitinib in an H292 tumor model by [(18)F]fluorothymidine-positron emission tomography. Invest New Drugs. 2013 Jun;31(3):506-15. doi: 10.1007/s10637-012-9874-y. Epub 2012 Sep 18. PubMed PMID: 22987020.
4: Hou X, Huang F, Macedo LF, Harrington SC, Reeves KA, Greer A, Finckenstein FG, Brodie A, Gottardis MM, Carboni JM, Haluska P. Dual IGF-1R/InsR inhibitor BMS-754807 synergizes with hormonal agents in treatment of estrogen-dependent breast cancer. Cancer Res. 2011 Dec 15;71(24):7597-607. doi: 10.1158/0008-5472.CAN-11-1080. Epub 2011 Oct 31. PubMed PMID: 22042792; PubMed Central PMCID: PMC4004036.
5: Kolb EA, Gorlick R, Lock R, Carol H, Morton CL, Keir ST, Reynolds CP, Kang MH, Maris JM, Billups C, Smith MA, Houghton PJ. Initial testing (stage 1) of the IGF-1 receptor inhibitor BMS-754807 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2011 Apr;56(4):595-603. doi: 10.1002/pbc.22741. Epub 2010 Dec 22. PubMed PMID: 21298745.
6: Huang F, Hurlburt W, Greer A, Reeves KA, Hillerman S, Chang H, Fargnoli J, Graf Finckenstein F, Gottardis MM, Carboni JM. Differential mechanisms of acquired resistance to insulin-like growth factor-i receptor antibody therapy or to a small-molecule inhibitor, BMS-754807, in a human rhabdomyosarcoma model. Cancer Res. 2010 Sep 15;70(18):7221-31. doi: 10.1158/0008-5472.CAN-10-0391. Epub 2010 Aug 31. PubMed PMID: 20807811.
7: Dinchuk JE, Cao C, Huang F, Reeves KA, Wang J, Myers F, Cantor GH, Zhou X, Attar RM, Gottardis M, Carboni JM. Insulin receptor (IR) pathway hyperactivity in IGF-IR null cells and suppression of downstream growth signaling using the dual IGF-IR/IR inhibitor, BMS-754807. Endocrinology. 2010 Sep;151(9):4123-32. doi: 10.1210/en.2010-0032. Epub 2010 Jul 7. PubMed PMID: 20610571.
8: Carboni JM, Wittman M, Yang Z, Lee F, Greer A, Hurlburt W, Hillerman S, Cao C, Cantor GH, Dell-John J, Chen C, Discenza L, Menard K, Li A, Trainor G, Vyas D, Kramer R, Attar RM, Gottardis MM. BMS-754807, a small molecule inhibitor of insulin-like growth factor-1R/IR. Mol Cancer Ther. 2009 Dec;8(12):3341-9. doi: 10.1158/1535-7163.MCT-09-0499. Epub . PubMed PMID: 19996272.
9: Wittman MD, Carboni JM, Yang Z, Lee FY, Antman M, Attar R, Balimane P, Chang C, Chen C, Discenza L, Frennesson D, Gottardis MM, Greer A, Hurlburt W, Johnson W, Langley DR, Li A, Li J, Liu P, Mastalerz H, Mathur A, Menard K, Patel K, Sack J, Sang X, Saulnier M, Smith D, Stefanski K, Trainor G, Velaparthi U, Zhang G, Zimmermann K, Vyas DM. Discovery of a 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitor (BMS-754807) of insulin-like growth factor receptor (IGF-1R) kinase in clinical development. J Med Chem. 2009 Dec 10;52(23):7360-3. doi: 10.1021/jm900786r. PubMed PMID: 19778024.
2: Awasthi N, Zhang C, Ruan W, Schwarz MA, Schwarz RE. BMS-754807, a small-molecule inhibitor of insulin-like growth factor-1 receptor/insulin receptor, enhances gemcitabine response in pancreatic cancer. Mol Cancer Ther. 2012 Dec;11(12):2644-53. doi: 10.1158/1535-7163.MCT-12-0447. Epub 2012 Oct 9. PubMed PMID: 23047891.
3: Lee SJ, Kim EJ, Lee HJ, Kim SY, Oh SJ, Ryu JS, Moon DH, Ahn JH, Kim SW. A pilot study for the early assessment of the effects of BMS-754807 plus gefitinib in an H292 tumor model by [(18)F]fluorothymidine-positron emission tomography. Invest New Drugs. 2013 Jun;31(3):506-15. doi: 10.1007/s10637-012-9874-y. Epub 2012 Sep 18. PubMed PMID: 22987020.
4: Hou X, Huang F, Macedo LF, Harrington SC, Reeves KA, Greer A, Finckenstein FG, Brodie A, Gottardis MM, Carboni JM, Haluska P. Dual IGF-1R/InsR inhibitor BMS-754807 synergizes with hormonal agents in treatment of estrogen-dependent breast cancer. Cancer Res. 2011 Dec 15;71(24):7597-607. doi: 10.1158/0008-5472.CAN-11-1080. Epub 2011 Oct 31. PubMed PMID: 22042792; PubMed Central PMCID: PMC4004036.
5: Kolb EA, Gorlick R, Lock R, Carol H, Morton CL, Keir ST, Reynolds CP, Kang MH, Maris JM, Billups C, Smith MA, Houghton PJ. Initial testing (stage 1) of the IGF-1 receptor inhibitor BMS-754807 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2011 Apr;56(4):595-603. doi: 10.1002/pbc.22741. Epub 2010 Dec 22. PubMed PMID: 21298745.
6: Huang F, Hurlburt W, Greer A, Reeves KA, Hillerman S, Chang H, Fargnoli J, Graf Finckenstein F, Gottardis MM, Carboni JM. Differential mechanisms of acquired resistance to insulin-like growth factor-i receptor antibody therapy or to a small-molecule inhibitor, BMS-754807, in a human rhabdomyosarcoma model. Cancer Res. 2010 Sep 15;70(18):7221-31. doi: 10.1158/0008-5472.CAN-10-0391. Epub 2010 Aug 31. PubMed PMID: 20807811.
7: Dinchuk JE, Cao C, Huang F, Reeves KA, Wang J, Myers F, Cantor GH, Zhou X, Attar RM, Gottardis M, Carboni JM. Insulin receptor (IR) pathway hyperactivity in IGF-IR null cells and suppression of downstream growth signaling using the dual IGF-IR/IR inhibitor, BMS-754807. Endocrinology. 2010 Sep;151(9):4123-32. doi: 10.1210/en.2010-0032. Epub 2010 Jul 7. PubMed PMID: 20610571.
8: Carboni JM, Wittman M, Yang Z, Lee F, Greer A, Hurlburt W, Hillerman S, Cao C, Cantor GH, Dell-John J, Chen C, Discenza L, Menard K, Li A, Trainor G, Vyas D, Kramer R, Attar RM, Gottardis MM. BMS-754807, a small molecule inhibitor of insulin-like growth factor-1R/IR. Mol Cancer Ther. 2009 Dec;8(12):3341-9. doi: 10.1158/1535-7163.MCT-09-0499. Epub . PubMed PMID: 19996272.
9: Wittman MD, Carboni JM, Yang Z, Lee FY, Antman M, Attar R, Balimane P, Chang C, Chen C, Discenza L, Frennesson D, Gottardis MM, Greer A, Hurlburt W, Johnson W, Langley DR, Li A, Li J, Liu P, Mastalerz H, Mathur A, Menard K, Patel K, Sack J, Sang X, Saulnier M, Smith D, Stefanski K, Trainor G, Velaparthi U, Zhang G, Zimmermann K, Vyas DM. Discovery of a 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitor (BMS-754807) of insulin-like growth factor receptor (IGF-1R) kinase in clinical development. J Med Chem. 2009 Dec 10;52(23):7360-3. doi: 10.1021/jm900786r. PubMed PMID: 19778024.
| Chemical | |
|---|---|
| CAS Num | 1001350-96-4 |
| Chemical Formula | C23H24FN9O |
| Molecular Weight | 461.49 |
| IUPAC Chemical Name | (S)-1-(4-((5-cyclopropyl-1H-pyrazol-3-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide. |
| Exact Mass | 461.20878 |
| Elemental Analysis | C, 59.86; H, 5.24; F, 4.12; N, 27.32; O, 3.47 |
| Synonym | BMS754807; BMS-754807; BMS 754807. |
| Solubility | Soluble in DMSO, not in water |
| SMILES Code | O=C([C@@]1(C)N(C(N=C2NC3=NNC(C4CC4)=C3)=NN5C2=CC=C5)CCC1)NC6=CC=C(F)N=C6 |
| Biological | |
| Targets and Effects | IGF-1R |
| Pathways | Apoptosis |
| Physical | |
| 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). |
| Shelf Life | >2 years if stored properly |
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