AMG-900
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MedKoo CAT#: 204370

CAS#: 945595-80-2 (free base)

Description: AMG 900 is a small-molecule inhibitor of Aurora kinases A, B and C with potential antineoplastic activity. Aurora kinase inhibitor AMG 900 selectively binds to and inhibits the activities of Aurora kinases A, B and C, which may result in inhibition of cellular division and proliferation in tumor cells that overexpress these kinases. Aurora kinases are serine-threonine kinases that play essential roles in mitotic checkpoint control during mitosis and are overexpressed by a wide variety of cancer cell types.


Chemical Structure

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AMG-900
CAS# 945595-80-2 (free base)

Theoretical Analysis

MedKoo Cat#: 204370
Name: AMG-900
CAS#: 945595-80-2 (free base)
Chemical Formula: C28H21N7OS
Exact Mass: 503.15
Molecular Weight: 503.578
Elemental Analysis: C, 66.78; H, 4.20; N, 19.47; O, 3.18; S, 6.37

Price and Availability

Size Price Availability Quantity
100mg USD 450
200mg USD 850
500mg USD 1750
1g USD 2950
2g USD 4950
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Related CAS #: Amg-900 bismesylate dihydrate   945595-80-2 (free base)  

Synonym: AMG900; AMG-900; AMG 900.

IUPAC/Chemical Name: N-(4-((3-(2-aminopyrimidin-4-yl)pyridin-2-yl)oxy)phenyl)-4-(4-methylthiophen-2-yl)phthalazin-1-amine.

InChi Key: IVUGFMLRJOCGAS-UHFFFAOYSA-N

InChi Code: InChI=1S/C28H21N7OS/c1-17-15-24(37-16-17)25-20-5-2-3-6-21(20)26(35-34-25)32-18-8-10-19(11-9-18)36-27-22(7-4-13-30-27)23-12-14-31-28(29)33-23/h2-16H,1H3,(H,32,35)(H2,29,31,33)

SMILES Code: CC1=CSC(C2=NN=C(NC3=CC=C(OC4=NC=CC=C4C5=NC(N)=NC=C5)C=C3)C6=C2C=CC=C6)=C1

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: >5 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: MG 900 is an orally bioavailable, potent, and highly selective pan-aurora kinase inhibitor that is active in taxane-resistant tumor cell lines. In tumor cells, AMG 900 inhibited autophosphorylation of aurora-A and -B as well as phosphorylation of histone H3 on Ser10, a proximal substrate of aurora-B. The predominant cellular response of tumor cells to AMG 900 treatment was aborted cell division without a prolonged mitotic arrest, which ultimately resulted in cell death. AMG 900 inhibited the proliferation of 26 tumor cell lines, including cell lines resistant to the antimitotic drug paclitaxel and to other aurora kinase inhibitors (AZD1152, MK-0457, and PHA-739358), at low nanomolar concentrations. Furthermore, AMG 900 was active in an AZD1152-resistant HCT116 variant cell line that harbors an aurora-B mutation (W221L). Oral administration of AMG 900 blocked the phosphorylation of histone H3 in a dose-dependent manner and significantly inhibited the growth of HCT116 tumor xenografts. Importantly, AMG 900 was broadly active in multiple xenograft models, including 3 multidrug-resistant xenograft models, representing 5 tumor types. AMG 900 has entered clinical evaluation in adult patients with advanced cancers and has the potential to treat tumors refractory to anticancer drugs such as the taxanes. (Source: Cancer Res; 70(23); 9846–54.)       

Product Data:
Biological target: AMG 900 is a pan-Aurora kinases inhibitor with IC50 of 5 nM, 4 nM and 1 nM for Aurora A, B and C, respectively.
In vitro activity: Treatment with AMG900 reduced growth of A172, U‐87MG, and U‐118MG cells in a concentration‐dependent manner (from 0.1 to 100 nmol/L; Figure 1A). In addition, while the number of DMSO‐treated control cells increased in a time‐dependent manner (from 24 to 120 hours), this was not the case for 100 nmol/L AMG900‐treated cells (Figure 1B). To examine the long‐term effects of AMG900, we exposed A172 cells to AMG900 for 24 hours, washed out drug, and examined colony formation after 14 days. AMG900‐treated cells showed significantly lower colony‐forming activity than control cells (Figure 1C), suggesting that short‐term exposure results in irreversible defects in survival. Overall, the data indicate that AMG900 reduces the proliferation of glioblastoma cells. Reference: Cancer Med. 2018 Nov; 7(11): 5589–5603. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246935/
In vivo activity: As measured by whole body bioluminescence, mice treated with AMG 900 using either dose schedule showed significant anti-tumor activity across study time points relative to vehicle-treated group [tumor growth inhibition 86–90% and 94%, P < .0001 (days 6 and 9); 95%, P < 0.02 (day 12)] (Fig. 5B). Relative to vehicle-treated group, AMG 900 significantly reduced the MOLM-13 cell fraction in the marrow (P ≤ 0.0002) (Fig. 5D), with 7-day schedule reducing tumor burden to a greater degree than the 4-day schedule (P = 0.0152). Reference: Mol Cancer Ther. 2018 Dec; 17(12): 2575–2585. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279493/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 55.0 109.22
DMF 15.0 29.79
DMF:PBS (pH 7.2) (1:3) 0.3 0.50

Preparing Stock Solutions

The following data is based on the product molecular weight 503.58 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: 1. Ryu J, Pyo J, Lee CW, Kim JE. An Aurora kinase inhibitor, AMG900, inhibits glioblastoma cell proliferation by disrupting mitotic progression. Cancer Med. 2018 Nov;7(11):5589-5603. doi: 10.1002/cam4.1771. Epub 2018 Sep 17. PMID: 30221846; PMCID: PMC6246935. 2. Borges KS, Andrade AF, Silveira VS, Marco Antonio DS, Vasconcelos EJR, Antonini SRR, Tone LG, Scrideli CA. The aurora kinase inhibitor AMG 900 increases apoptosis and induces chemosensitivity to anticancer drugs in the NCI-H295 adrenocortical carcinoma cell line. Anticancer Drugs. 2017 Jul;28(6):634-644. doi: 10.1097/CAD.0000000000000504. PMID: 28410270. 3. Payton M, Cheung HK, Ninniri MSS, Marinaccio C, Wayne WC, Hanestad K, Crispino JD, Juan G, Coxon A. Dual Targeting of Aurora Kinases with AMG 900 Exhibits Potent Preclinical Activity Against Acute Myeloid Leukemia with Distinct Post-Mitotic Outcomes. Mol Cancer Ther. 2018 Dec;17(12):2575-2585. doi: 10.1158/1535-7163.MCT-18-0186. Epub 2018 Sep 28. PMID: 30266802; PMCID: PMC6279493. 4. Juan G, Bush TL, Ma C, Manoukian R, Chung G, Hawkins JM, Zoog S, Kendall R, Radinsky R, Loberg R, Friberg G, Payton M. AMG 900, a potent inhibitor of aurora kinases causes pharmacodynamic changes in p-Histone H3 immunoreactivity in human tumor xenografts and proliferating mouse tissues. J Transl Med. 2014 Nov 4;12:307. doi: 10.1186/s12967-014-0307-x. PMID: 25367255; PMCID: PMC4221688.
In vitro protocol: 1. Ryu J, Pyo J, Lee CW, Kim JE. An Aurora kinase inhibitor, AMG900, inhibits glioblastoma cell proliferation by disrupting mitotic progression. Cancer Med. 2018 Nov;7(11):5589-5603. doi: 10.1002/cam4.1771. Epub 2018 Sep 17. PMID: 30221846; PMCID: PMC6246935. 2. Borges KS, Andrade AF, Silveira VS, Marco Antonio DS, Vasconcelos EJR, Antonini SRR, Tone LG, Scrideli CA. The aurora kinase inhibitor AMG 900 increases apoptosis and induces chemosensitivity to anticancer drugs in the NCI-H295 adrenocortical carcinoma cell line. Anticancer Drugs. 2017 Jul;28(6):634-644. doi: 10.1097/CAD.0000000000000504. PMID: 28410270.
In vivo protocol: 1. Payton M, Cheung HK, Ninniri MSS, Marinaccio C, Wayne WC, Hanestad K, Crispino JD, Juan G, Coxon A. Dual Targeting of Aurora Kinases with AMG 900 Exhibits Potent Preclinical Activity Against Acute Myeloid Leukemia with Distinct Post-Mitotic Outcomes. Mol Cancer Ther. 2018 Dec;17(12):2575-2585. doi: 10.1158/1535-7163.MCT-18-0186. Epub 2018 Sep 28. PMID: 30266802; PMCID: PMC6279493. 2. Juan G, Bush TL, Ma C, Manoukian R, Chung G, Hawkins JM, Zoog S, Kendall R, Radinsky R, Loberg R, Friberg G, Payton M. AMG 900, a potent inhibitor of aurora kinases causes pharmacodynamic changes in p-Histone H3 immunoreactivity in human tumor xenografts and proliferating mouse tissues. J Transl Med. 2014 Nov 4;12:307. doi: 10.1186/s12967-014-0307-x. PMID: 25367255; PMCID: PMC4221688.

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1: Waldon D, Berry L, Lin MH, Schenkel L, Hollis LS, Zhao Z. Gender Effects on Rat Metabolism of AMG 900, an Orally Available Small Molecule Aurora Kinase Inhibitor. Drug Metab Lett. 2011 Oct 21. [Epub ahead of print] PubMed PMID: 22022868.

2: Huang L, Be X, Berry L, Moore E, Janosky B, Wells M, Pan WJ, Zhao Z, Lin MH. In vitro and in vivo pharmacokinetic characterizations of AMG 900, an orally bioavailable small molecule inhibitor of aurora kinases. Xenobiotica. 2011 May;41(5):400-8. Epub 2011 Feb 4. PubMed PMID: 21294625.

3: Payton M, Bush TL, Chung G, Ziegler B, Eden P, McElroy P, Ross S, Cee VJ, Deak HL, Hodous BL, Nguyen HN, Olivieri PR, Romero K, Schenkel LB, Bak A, Stanton M, Dussault I, Patel VF, Geuns-Meyer S, Radinsky R, Kendall RL. Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. Cancer Res. 2010 Dec 1;70(23):9846-54. Epub 2010 Oct 8. PubMed PMID: 20935223.