Synonym
AZ628; AZ-628; AZ 628
IUPAC/Chemical Name
3-(Cyano-dimethyl-methyl)-N-[4-methyl-3-(3-methyl-4-oxo-3,4-dihydro-quinazolin-6-ylamino)-phenyl]-benzamide
InChi Key
ZGBGPEDJXCYQPH-UHFFFAOYSA-N
InChi Code
InChI=1S/C27H25N5O2/c1-17-8-9-21(31-25(33)18-6-5-7-19(12-18)27(2,3)15-28)14-24(17)30-20-10-11-23-22(13-20)26(34)32(4)16-29-23/h5-14,16,30H,1-4H3,(H,31,33)
SMILES Code
O=C(NC1=CC=C(C)C(NC2=CC3=C(N=CN(C)C3=O)C=C2)=C1)C4=CC=CC(C(C)(C#N)C)=C4
Appearance
white 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
Biological target:
AZ 628 is a pan-Raf kinase inhibitor with IC50s of 105, 34 and 29 nM for B-Raf, B-RafV600E, and c-Raf-1, respectively.
In vitro activity:
Based on the results displayed in Figure 2, AZ-628 at the concentration of 1 or 3 μM significantly reversed the resistance to mitoxantrone, SN-38 and topotecan in H460/MX20 (Figures 2A,C,E) and S1-M1-80 (Figures 2B,D,F) cells. It is noteworthy that AZ-628 at 3 μM showed better reversal effects than the positive ABCG2 modulator KO143 in both H460/MX20 and S1-M1-80. AZ-628 did not alter the cytotoxicity of cisplatin, a non-substrate of ABCG2.
Reference: Front Cell Dev Biol. 2020; 8: 601400. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753047/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
53.8 |
119.13 |
| DMSO:PBS (pH 7.2) (1:1) |
0.5 |
1.11 |
| DMF |
25.0 |
55.37 |
| Ethanol |
0.3 |
0.55 |
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
451.52
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.
| 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. Wang JQ, Teng QX, Lei ZN, Ji N, Cui Q, Fu H, Lin L, Yang DH, Fan YF, Chen ZS. Reversal of Cancer Multidrug Resistance (MDR) Mediated by ATP-Binding Cassette Transporter G2 (ABCG2) by AZ-628, a RAF Kinase Inhibitor. Front Cell Dev Biol. 2020 Dec 8;8:601400. doi: 10.3389/fcell.2020.601400. PMID: 33364237; PMCID: PMC7753047.
2. Jeon J, Noh HJ, Lee H, Park HH, Ha YJ, Park SH, Lee H, Kim SJ, Kang HC, Eyun SI, Yang S, Kim YS. TRIM24-RIP3 axis perturbation accelerates osteoarthritis pathogenesis. Ann Rheum Dis. 2020 Dec;79(12):1635-1643. doi: 10.1136/annrheumdis-2020-217904. Epub 2020 Sep 7. PMID: 32895234; PMCID: PMC7677493.
In vitro protocol:
1. Wang JQ, Teng QX, Lei ZN, Ji N, Cui Q, Fu H, Lin L, Yang DH, Fan YF, Chen ZS. Reversal of Cancer Multidrug Resistance (MDR) Mediated by ATP-Binding Cassette Transporter G2 (ABCG2) by AZ-628, a RAF Kinase Inhibitor. Front Cell Dev Biol. 2020 Dec 8;8:601400. doi: 10.3389/fcell.2020.601400. PMID: 33364237; PMCID: PMC7753047.
2. Jeon J, Noh HJ, Lee H, Park HH, Ha YJ, Park SH, Lee H, Kim SJ, Kang HC, Eyun SI, Yang S, Kim YS. TRIM24-RIP3 axis perturbation accelerates osteoarthritis pathogenesis. Ann Rheum Dis. 2020 Dec;79(12):1635-1643. doi: 10.1136/annrheumdis-2020-217904. Epub 2020 Sep 7. PMID: 32895234; PMCID: PMC7677493.
1: Whittaker SR, Theurillat JP, Van Allen E, Wagle N, Hsiao J, Cowley GS, Schadendorf D, Root DE, Garraway LA. A genome-scale RNA interference screen implicates NF1 loss in resistance to RAF inhibition. Cancer Discov. 2013 Jan 3. [Epub ahead of print] PubMed PMID: 23288408.
2: Montagut C, Sharma SV, Shioda T, McDermott U, Ulman M, Ulkus LE, Dias-Santagata D, Stubbs H, Lee DY, Singh A, Drew L, Haber DA, Settleman J. Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma. Cancer Res. 2008 Jun 15;68(12):4853-61. doi: 10.1158/0008-5472.CAN-07-6787. PubMed PMID: 18559533; PubMed Central PMCID: PMC2692356.
