- AXL1717
- NVP-ADW742
- AG-1024
- LDK378 dihydrochloride
- Linsitinib
- BMS-536924
| BMS-754807IGF-1R/InsR inhibitor,potent and selective |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
Nature.2018 Nov;563(7731):407-411.Nature.2018 Jun 13.Nature.2018 Jun 27.Nature.2018 Mar 29;555(7698):673-677.Nature.2017 Sep 7;549(7670):96-100.Nature.2016 Apr 21;532(7599):398-401.
Science.2016 Aug 5;353(6299)594-8Nat Nanotechnol.2017 Dec;12(12):1190-1198.Nature Biotechnology.2017 Jun;35(6):569-576Nat Med.2018 Sep 17.Cell.2018 Dec 21. pii: S0092-8674(18)31561-7.Cell.Available online 25 October 2018.Cell.2018 Sep 27. pii: S0092-8674(18)31183-8.Cell.2018 Jun 28;174(1):172-186.e21.Cell.2018 Feb 22;172(5):1007-1021.e17.Cell.2017 Nov 30;171(6):1284-1300.e21.Cell.2017 Aug 17. pii: S0092-8674(17)30869-3.Cell.2017 Jul 13;170(2):312-323Nat Med.2018 Jan 29.Nat Med.2017 Nov;23(11):1342-1351.Cell.2017 Apr 6;169(2):286-300.Cell.2015 Aug 27;162(5):987-1002.Cell.2015 Feb 12;160(4):729-44.Nature Medicine.2017 Apr;23(4):493-500.Cancer Cell.2018 May 14;33(5):905-921.e5.Cancer Cell.2018 Apr 9;33(4):752-769.e8.Cancer Cell.2018 Mar 12;33(3):401-416.e8.Cancer Cell.2017 Aug 14;32(2):253-267.e5.Nat Methods.2018 Jul;15(7):523-526.Cell Stem Cell.2018 May 3;22(5):769-778.e4.Cell Stem Cell.2017 Nov 20. pii: S1934-5909(17)30375-2.Quality Control & MSDS
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- Purity = 99.53%
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- Datasheet
Chemical structure
| Description | BMS-754807 is a potent and selective inhibitor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor family kinase (InsR) with IC50 values of 1.8 nM and 1.7 nM, respectively. | |||||
| Targets | IGF-1R | InsR | ||||
| IC50 | 1.8 nM | 1.7 nM | ||||
| Cell experiment: [1] | |
Cell lines | IGF-1R-Sal, Rh41 and Geo cells |
Preparation method | The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
Reaction Conditions | 1 μM, (72 hours for cell proliferation inhibition; 1 hour for phosphorylation inhibition |
Applications | Cell proliferation was evaluated by incorporation of 3H-thymidine into DNA after exposure of cells to BMS-754807 with concentrations from 0.1 to 1000 nM. BMS-754807 inhibited cell proliferation with IC50 values of 7, 5 and 365 nM for IGF-1R-Sal, Rh41 and Geo cells, respectively. The IC50 values for inhibition of the pIGF-1R by BMS-754807 and downstream components (e.g., pAkt) were very similar. In contrast, there was greater inhibition against pMAPK in IGF-1R-Sal cells compared with Rh41 and Geo, indicating that additional compensatory pathways such as EGFR might be important in driving signals in both Rh41 and Geo cell types. |
| Animal experiment : [1] | |
Animal models | Nude mice bearing various tumor xenografts (Sal-IGF, GEO, Colo205, JJN3, Rh41 or RD1) |
Dosage form | Oral administration, 0.01 mL/g of body weight |
Applications | BMS-754807 inhibited tumor growth in a selected group of epithelial (IGF-1R-Sal, GEO and Colo205), hematopoietic (JJN3) and mesenchymal (RD1 and Rh41) xenograft tumor models with TGI ranging from 53% to 115%. In the highly sensitive Rh41 rhabdomyosarcoma, BMS-754807 was effective at a dose level of 3.125 mg/kg twice daily and as low as 6.25 mg/kg once daily. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: [1] Carboni J M, Wittman M, Yang Z, et al. BMS-754807, a small molecule inhibitor of insulin-like growth factor-1R/IR. Molecular Cancer Therapeutics, 2009, 8(12): 3341-3349. | |
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| Cas No. | 1001350-96-4 | SDF | Download SDF |
| Chemical Name | (2S)-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 | ||
| Canonical SMILES | CC1(CCCN1C2=NN3C=CC=C3C(=N2)NC4=NNC(=C4)C5CC5)C(=O)NC6=CN=C(C=C6)F | ||
| Formula | C23H24FN9O | M.Wt | 461.49 |
| Solubility | ≥23.05mg/mL in DMSO | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
BMS-754807 is a potent and small molecular inhibitor which targets the IGF-1R/IR family kinases with Ki <2 nmol/l[1].="" the="" efficacy="" of="" bms-754807="" on="" normal="" tissues="" and="" tumor="" cell="" cycle="" is="" believed="" to="" be="" different="" from="" the="" effects="" of="" continuous="" inhibition="" by="" anti-igf-1r="">
BMS-754807 could effectively inhibit the growth of many human tumor types from in vitro perspective, such as mesenchymal, hematopoietic and epithelial tumor cell lines with an IC50 value of 5–365 nmol/L. It can also induce sub-G1 fraction accumulation and an increase in poly ADP ribose polymerase and Caspase 3 cleavage, suggesting that it can lead to apoptosis in a human rhabdomyosarcoma cell line (Rh41). Furthermore, as a pyrrolotriazine and reversible ATP-competitive antagonist of IGF-1R, BMS-754807 was shown to inhibit the catalytic domain of the IGF-1R, and proved to inhibit the IGF-1R and IR activity by using the in-vitro kinase assays. Since the antibodies can bind to IGF-1R but not to IR, this could be regardere as an escape mechanism for IGF-II and insulin signaling.[3]
References:[1] Q.S. Chu，S.W. Kim，P.M. Ellis，L. Mileshkin，R.H. de Boer，J.S. Park，T. Pellas，F. Huang，F. Graf Finckenstein，A. Dhar. BMS-754807, an oral dual IGF-1R/insulin receptor (IR) inhibitor: initial results from a Phase 1 dose- and schedule-finding study in combination with carboplatin/paclitaxel in subjects with solid tumors. European Journal of Cancer Supplements. November 2010, 8(7): 131.[2] Vattoly J. Majo, Victoria Arango, Norman R. Simpson, Jaya Prabhakaran, Suham A. Kassir, Mark D. Underwood, Mihran Bakalian, Peter Canoll, J. John Mann, J.S. Dileep Kumar. Synthesis and in vitro evaluation of [18F]BMS-754807: A potential PET ligand for IGF-1R. Bioorganic & Medicinal Chemistry Letters. July 2013, 23(14): 4191-4194.[3] Joan M. Carboni, Mark Wittman, Zheng Yang, et al.. BMS-754807, a small molecule inhibitor of insulin-like growth factor-1R/IR. Mol Cancer Ther. 2009;8:3341-3349.
