BMS-777607 (BMS-817378)
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 200527

CAS#: 1025720-94-8

Description: BMS-777607, also known as BMS-817378 and ASLAN-002, a Met tyrosine kinase inhibitor, is an inhibitor of MET tyrosine kinase with potential antineoplastic activity. MET tyrosine kinase inhibitor BMS-777607 binds to c-Met protein, or hepatocyte growth factor receptor (HGFR), preventing binding of hepatocyte growth factor (HGF) and disrupting the MET signaling pathway; this agent may induce cell death in tumor cells expressing c-Met. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays an important role in tumor cell proliferation, survival, invasion, and metastasis, and in tumor angiogenesis.


Price and Availability

Size
Price

10mg
USD 150
100mg
USD 750
1g
USD 2950
Size
Price

25mg
USD 250
200mg
USD 1250
2g
USD 4250
Size
Price

50mg
USD 450
500mg
USD 2150
5g
USD 7450

BMS-777607, purity > 98%, is in stock. The same day shipping out after order is received. Note: the estimated shipping out time for order > 500mg may be 2 weeks.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 200527
Name: BMS-777607 (BMS-817378)
CAS#: 1025720-94-8
Chemical Formula: C25H19ClF2N4O4
Exact Mass: 512.10629
Molecular Weight: 512.89
Elemental Analysis: C, 58.54; H, 3.73; Cl, 6.91; F, 7.41; N, 10.92; O, 12.48


Related CAS #: 1025720-94-8   1196681-44-3 (deleted)    

Synonym: BMS817378; BMS 817378; BMS-817378; BMS 777607; BMS-777607; BMS777607; ASLAN 002; ASLAN-002; ASLAN002.

IUPAC/Chemical Name: N-(4-((2-amino-3-chloropyridin-4-yl)oxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide.

InChi Key: VNBRGSXVFBYQNN-UHFFFAOYSA-N

InChi Code: InChI=1S/C25H19ClF2N4O4/c1-2-35-19-10-12-32(16-6-3-14(27)4-7-16)25(34)21(19)24(33)31-15-5-8-18(17(28)13-15)36-20-9-11-30-23(29)22(20)26/h3-13H,2H2,1H3,(H2,29,30)(H,31,33)

SMILES Code: O=C(C1=C(OCC)C=CN(C2=CC=C(F)C=C2)C1=O)NC3=CC=C(OC4=C(Cl)C(N)=NC=C4)C(F)=C3


Technical Data

Appearance:
white solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Safety Data Sheet (MSDS):

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)

Solubility:
Soluble in DMSO at 40mg / mL, not soluble in water, not soluble in ethanol.

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


References

1: Onken J, Torka R, Korsing S, Radke J, Krementeskaia I, Nieminen M, Bai X, Ullrich A, Heppner F, Vajkoczy P. Inhibiting receptor tyrosine kinase AXL with small molecule inhibitor BMS-777607 reduces glioblastoma growth, migration, and invasion in vitro and in vivo. Oncotarget. 2016 Mar 1;7(9):9876-89. doi: 10.18632/oncotarget.7130. PubMed PMID: 26848524.

2: Chakedis J, French R, Babicky M, Jaquish D, Howard H, Mose E, Lam R, Holman P, Miyamoto J, Walterscheid Z, Lowy AM. A novel protein isoform of the RON tyrosine kinase receptor transforms human pancreatic duct epithelial cells. Oncogene. 2015 Oct 19. doi: 10.1038/onc.2015.384. [Epub ahead of print] PubMed PMID: 26477314; PubMed Central PMCID: PMC4837108.

3: Müller J, Krijgsman O, Tsoi J, Robert L, Hugo W, Song C, Kong X, Possik PA, Cornelissen-Steijger PD, Foppen MH, Kemper K, Goding CR, McDermott U, Blank C, Haanen J, Graeber TG, Ribas A, Lo RS, Peeper DS. Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma. Nat Commun. 2014 Dec 15;5:5712. doi: 10.1038/ncomms6712. PubMed PMID: 25502142; PubMed Central PMCID: PMC4428333.

4: Nurhayati RW, Ojima Y, Taya M. BMS-777607 promotes megakaryocytic differentiation and induces polyploidization in the CHRF-288-11 cells. Hum Cell. 2015 Apr;28(2):65-72. doi: 10.1007/s13577-014-0102-2. Epub 2014 Oct 11. PubMed PMID: 25304900.

5: Zhang W, Ai J, Shi D, Peng X, Ji Y, Liu J, Geng M, Li Y. Discovery of novel type II c-Met inhibitors based on BMS-777607. Eur J Med Chem. 2014 Jun 10;80:254-66. doi: 10.1016/j.ejmech.2014.04.056. Epub 2014 Apr 21. PubMed PMID: 24792774.

6: Szokol B, Gyulavári P, Baska F, Ibolya K, Greff Z, Szántai KC, Zoltán O, Peták I, Axel U, Vantus T, Kéri G, Orfi L. [Development and biochemical characterization of EGFR/c-Met dual inhibitors]. Acta Pharm Hung. 2013;83(4):121-33. Hungarian. PubMed PMID: 24575658.

7: Zhang W, Ai J, Shi D, Peng X, Ji Y, Liu J, Geng M, Li Y. Discovery of novel c-Met inhibitors bearing a 3-carboxyl piperidin-2-one scaffold. Molecules. 2014 Feb 24;19(2):2655-73. doi: 10.3390/molecules19022655. PubMed PMID: 24566328.

8: Sharma S, Yao HP, Zhou YQ, Zhou J, Zhang R, Wang MH. Prevention of BMS-777607-induced polyploidy/senescence by mTOR inhibitor AZD8055 sensitizes breast cancer cells to cytotoxic chemotherapeutics. Mol Oncol. 2014 May;8(3):469-82. doi: 10.1016/j.molonc.2013.12.014. Epub 2014 Jan 2. PubMed PMID: 24444656.

9: Traoré T, Cavagnino A, Saettel N, Radvanyi F, Piguel S, Bernard-Pierrot I, Stoven V, Legraverend M. New aminopyrimidine derivatives as inhibitors of the TAM family. Eur J Med Chem. 2013;70:789-801. doi: 10.1016/j.ejmech.2013.10.037. Epub 2013 Oct 22. PubMed PMID: 24239626.

10: Zeng JY, Sharma S, Zhou YQ, Yao HP, Hu X, Zhang R, Wang MH. Synergistic activities of MET/RON inhibitor BMS-777607 and mTOR inhibitor AZD8055 to polyploid cells derived from pancreatic cancer and cancer stem cells. Mol Cancer Ther. 2014 Jan;13(1):37-48. doi: 10.1158/1535-7163.MCT-13-0242. Epub 2013 Nov 14. PubMed PMID: 24233399.

11: Sharma S, Zeng JY, Zhuang CM, Zhou YQ, Yao HP, Hu X, Zhang R, Wang MH. Small-molecule inhibitor BMS-777607 induces breast cancer cell polyploidy with increased resistance to cytotoxic chemotherapy agents. Mol Cancer Ther. 2013 May;12(5):725-36. doi: 10.1158/1535-7163.MCT-12-1079. Epub 2013 Mar 6. PubMed PMID: 23468529.

12: Voortman J, Harada T, Chang RP, Killian JK, Suuriniemi M, Smith WI, Meltzer PS, Lucchi M, Wang Y, Giaccone G. Detection and therapeutic implications of c-Met mutations in small cell lung cancer and neuroendocrine tumors. Curr Pharm Des. 2013;19(5):833-40. PubMed PMID: 22973954.

13: Gujral TS, Karp RL, Finski A, Chan M, Schwartz PE, MacBeath G, Sorger P. Profiling phospho-signaling networks in breast cancer using reverse-phase protein arrays. Oncogene. 2013 Jul 18;32(29):3470-6. doi: 10.1038/onc.2012.378. Epub 2012 Sep 3. PubMed PMID: 22945653; PubMed Central PMCID: PMC3670968.

14: Suárez RM, Chevot F, Cavagnino A, Saettel N, Radvanyi F, Piguel S, Bernard-Pierrot I, Stoven V, Legraverend M. Inhibitors of the TAM subfamily of tyrosine kinases: synthesis and biological evaluation. Eur J Med Chem. 2013 Mar;61:2-25. doi: 10.1016/j.ejmech.2012.06.005. Epub 2012 Jun 12. PubMed PMID: 22749189.

15: Dai Y, Siemann DW. Constitutively active c-Met kinase in PC-3 cells is autocrine-independent and can be blocked by the Met kinase inhibitor BMS-777607. BMC Cancer. 2012 May 28;12:198. doi: 10.1186/1471-2407-12-198. PubMed PMID: 22639908; PubMed Central PMCID: PMC3418572.

16: Dai Y, Bae K, Pampo C, Siemann DW. Impact of the small molecule Met inhibitor BMS-777607 on the metastatic process in a rodent tumor model with constitutive c-Met activation. Clin Exp Metastasis. 2012 Mar;29(3):253-61. doi: 10.1007/s10585-011-9447-z. PubMed PMID: 22286523.

17: Dai Y, Siemann DW. BMS-777607, a small-molecule met kinase inhibitor, suppresses hepatocyte growth factor-stimulated prostate cancer metastatic phenotype in vitro. Mol Cancer Ther. 2010 Jun;9(6):1554-61. doi: 10.1158/1535-7163.MCT-10-0359. Epub 2010 Jun 1. PubMed PMID: 20515943.

18: Schroeder GM, An Y, Cai ZW, Chen XT, Clark C, Cornelius LA, Dai J, Gullo-Brown J, Gupta A, Henley B, Hunt JT, Jeyaseelan R, Kamath A, Kim K, Lippy J, Lombardo LJ, Manne V, Oppenheimer S, Sack JS, Schmidt RJ, Shen G, Stefanski K, Tokarski JS, Trainor GL, Wautlet BS, Wei D, Williams DK, Zhang Y, Zhang Y, Fargnoli J, Borzilleri RM. Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl )-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a selective and orally efficacious inhibitor of the Met kinase superfamily. J Med Chem. 2009 Mar 12;52(5):1251-4. doi: 10.1021/jm801586s. PubMed PMID: 19260711.