WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406110
CAS#: 878739-06-1
Description: AZ-628 is a selective, orally available Raf inhibitor with excellent pharmacokinetic properties and robust tumor growth inhibition in xenograft studies ( (IC50 values are 29, 34 and 105 nM for c-Raf1, B-RafV600E and wild-type B-Raf, respectively). AZ-628 inhibits growth, and induces cell cycle arrest and apoptosis in colon and melanoma cell lines with the B-RafV600E mutation.
MedKoo Cat#: 406110
Name: AZ-628
CAS#: 878739-06-1
Chemical Formula: C27H25N5O2
Exact Mass: 451.20083
Molecular Weight: 451.5197
Elemental Analysis: C, 71.82; H, 5.58; N, 15.51; O, 7.09
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/ |
| In vivo activity: | TBD |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 53.79 | 119.13 | |
| DMSO:PBS (pH 7.2) (1:1) | 0.5 | 1.11 | |
| DMF | 25.0 | 55.37 | |
| Ethanol | 0.25 | 0.55 |
The following data is based on the product molecular weight 451.5197 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. |
| In vivo protocol: | TBD |
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.
