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MedKoo Cat#: 204320 | Name: AMG-337
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

AMG 337 is an orally bioavailable inhibitor of the proto-oncogene c-Met with potential antineoplastic activity. c-Met inhibitor AMG 337 selectively binds to c-Met, thereby disrupting c-Met signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein.

Chemical Structure

AMG-337
AMG-337
CAS#1173699-31-4 (free base)

Theoretical Analysis

MedKoo Cat#: 204320

Name: AMG-337

CAS#: 1173699-31-4 (free base)

Chemical Formula: C23H22FN7O3

Exact Mass: 463.1768

Molecular Weight: 463.47

Elemental Analysis: C, 59.60; H, 4.78; F, 4.10; N, 21.16; O, 10.36

Price and Availability

Size Price Availability Quantity
5mg USD 90.00 Ready to ship
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,350.00 Ready to ship
500mg USD 2,850.00 Ready to ship
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Related CAS #
1173699-31-4 (free base) 1643590-78-6 (monohydrate)
Synonym
AMG337; AMG-337; AMG 337.
IUPAC/Chemical Name
(R)-6-(1-(8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)ethyl)-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one
InChi Key
DWHXUGDWKAIASB-CQSZACIVSA-N
InChi Code
InChI=1S/C23H22FN7O3/c1-14(30-5-4-20-18(23(30)32)9-17(11-25-20)34-7-6-33-3)21-27-28-22-19(24)8-15(13-31(21)22)16-10-26-29(2)12-16/h4-5,8-14H,6-7H2,1-3H3/t14-/m1/s1
SMILES Code
O=C1C2=C(N=CC(OCCOC)=C2)C=CN1[C@@H](C3=NN=C4C(F)=CC(C5=CN(C)N=C5)=CN43)C
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).
Solubility
Soluble in DMSO, not in water
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).
HS Tariff Code
2934.99.9001
More Info
       
Biological target:
AMG-337 is a potent and highly selective small molecule ATP-competitive MET kinase inhibitor with an IC50 of < 5nM in enzymatic assays.
In vitro activity:
The effect of AMG 337 on cell proliferation was examined in a panel of 22 cancer cell lines that were reported to have elevated MET gene copy number, only 2 of which, SNU-5 and Hs746T, overlapped with the larger 260 cell line panel profiled with Compound 5 (Supplementary Table S2; ref. 27). Growth conditions for each cell line were optimized and cell viability was assessed following 72 hours of treatment with AMG 337. In addition, array CGH analysis was performed to quantify and confirm MET gene copy number, and cell lysates were generated to measure levels of total and phosphorylated MET protein. Nine cell lines exhibited sensitivity to AMG 337, (IC50 < 50 nmol/L; Fig. 1B and C), whereas the remaining cell lines were insensitive (IC50 > 3 μmol/L). A strong correlation was observed between high-level focal amplification of MET [aCGH log2 ratio of >2.5 (copy number >12), amplicon size
In vivo activity:
Daily oral administration was used to evaluate the in vivo antitumor activity of AMG 337 in two patient-derived xenograft (PDX) models of hepatocellular carcinoma (LI0612 and LI1078). AMG 337 exerted potent antiproliferative activity against 2 of 40 hepatocellular carcinoma cell lines, namely, MHCC97H (IC50, 0.015 μmol/L) and HCCLM3 (IC50, 0.025 μmol/L). Both sensitive cell lines showed MET amplification (MET/CEN-7 >2.0) assessed by FISH, and high MET expression (3+ IHC) assessed by IHC. AMG 337 potently inhibited p-MET in all cell lines with detectable levels of total MET. However, the dose-dependent inhibition of downstream effectors of HGF/MET signaling, including p-GAB1, p-AKT, and p-ERK, was limited to those cell lines sensitive to AMG 337 in a viability assay (MHCC97H and HCCLM3). AMG 337 significantly inhibited tumor growth at all doses tested in the MET-amplified and MET-high-expressing hepatocellular carcinoma PDX model LI0612 and had no effect on tumor growth in the non-MET-amplified and MET-low-expressing hepatocellular carcinoma PDX model LI1078. Reference: Mol Cancer Ther. 2016 Jun;15(6):1227-37. http://mct.aacrjournals.org/cgi/pmidlookup?view=long&pmid=27196749
Solvent mg/mL mM comments
Solubility
DMSO 50.0 107.88
Ethanol 50.0 107.88
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 463.47 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol:
1. Hughes PE, Rex K, Caenepeel S, Yang Y, Zhang Y, Broome MA, Kha HT, Burgess TL, Amore B, Kaplan-Lefko PJ, Moriguchi J, Werner J, Damore MA, Baker D, Choquette DM, Harmange JC, Radinsky R, Kendall R, Dussault I, Coxon A. In Vitro and In Vivo Activity of AMG 337, a Potent and Selective MET Kinase Inhibitor, in MET-Dependent Cancer Models. Mol Cancer Ther. 2016 Jul;15(7):1568-79. doi: 10.1158/1535-7163.MCT-15-0871. Epub 2016 Apr 19. PMID: 27196782. 2. Du Z, Caenepeel S, Shen Y, Rex K, Zhang Y, He Y, Tang ET, Wang O, Zhong W, Zhou H, Huang J, Huang E, Hu L, Coxon A, Zhang M. Preclinical Evaluation of AMG 337, a Highly Selective Small Molecule MET Inhibitor, in Hepatocellular Carcinoma. Mol Cancer Ther. 2016 Jun;15(6):1227-37. doi: 10.1158/1535-7163.MCT-15-0745. Epub 2016 Mar 29. PMID: 27196749.
In vivo protocol:
1. Du Z, Caenepeel S, Shen Y, Rex K, Zhang Y, He Y, Tang ET, Wang O, Zhong W, Zhou H, Huang J, Huang E, Hu L, Coxon A, Zhang M. Preclinical Evaluation of AMG 337, a Highly Selective Small Molecule MET Inhibitor, in Hepatocellular Carcinoma. Mol Cancer Ther. 2016 Jun;15(6):1227-37. doi: 10.1158/1535-7163.MCT-15-0745. Epub 2016 Mar 29. PMID: 27196749. 2. Hughes PE, Rex K, Caenepeel S, Yang Y, Zhang Y, Broome MA, Kha HT, Burgess TL, Amore B, Kaplan-Lefko PJ, Moriguchi J, Werner J, Damore MA, Baker D, Choquette DM, Harmange JC, Radinsky R, Kendall R, Dussault I, Coxon A. In Vitro and In Vivo Activity of AMG 337, a Potent and Selective MET Kinase Inhibitor, in MET-Dependent Cancer Models. Mol Cancer Ther. 2016 Jul;15(7):1568-79. doi: 10.1158/1535-7163.MCT-15-0871. Epub 2016 Apr 19. PMID: 27196782.
  1: Lee J, Tran P, Klempner SJ. Targeting the MET Pathway in Gastric and Oesophageal Cancers: Refining the Optimal Approach. Clin Oncol (R Coll Radiol). 2016 Feb 12. pii: S0936-6555(16)00035-2. doi: 10.1016/j.clon.2016.01.009. [Epub ahead of print] PubMed PMID: 26880063. 2: Boezio AA, Copeland KW, Rex K, K Albrecht B, Bauer D, Bellon SF, Boezio C, Broome MA, Choquette D, Coxon A, Dussault I, Hirai S, Lewis R, Lin MJ, Lohman J, Liu J, Peterson EA, Potashman M, Shimanovich R, Teffera Y, Whittington DA, Vaida KR, Harmange JC. Discovery of (R)-6-(1-(8-Fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-y l)ethyl)-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one (AMG 337), a Potent and Selective Inhibitor of MET with High Unbound Target Coverage and Robust In Vivo Antitumor Activity. J Med Chem. 2016 Feb 11. [Epub ahead of print] PubMed PMID: 26812066. 3: Aprile G, Leone F, Giampieri R, Casagrande M, Marino D, Faloppi L, Cascinu S, Fasola G, Scartozzi M. Tracking the 2015 Gastrointestinal Cancers Symposium: bridging cancer biology to clinical gastrointestinal oncology. Onco Targets Ther. 2015 May 22;8:1149-56. doi: 10.2147/OTT.S82624. eCollection 2015. Review. PubMed PMID: 26045669; PubMed Central PMCID: PMC4447178.