Synonym
AZM475271; AZM-475271; AZM 475271.
IUPAC/Chemical Name
N-(2-chloro-5-methoxyphenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine
InChi Key
WPOXAFXHRJYEIC-UHFFFAOYSA-N
InChi Code
InChI=1S/C23H27ClN4O3/c1-28-8-6-15(7-9-28)13-31-22-12-19-17(11-21(22)30-3)23(26-14-25-19)27-20-10-16(29-2)4-5-18(20)24/h4-5,10-12,14-15H,6-9,13H2,1-3H3,(H,25,26,27)
SMILES Code
CN1CCC(COC2=CC3=NC=NC(NC4=CC(OC)=CC=C4Cl)=C3C=C2OC)CC1
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
Treatment with AZM475271 alone reduced the primary pancreatic tumor volume by approximately 40%, whereas AZM475271 plus gemcitabine reduced tumor volume by 90%. Furthermore, treatment with AZM475271 and gemcitabine significantly reduced metastasis: none of eight animals who received the combination treatment had lymph node or liver metastases, compared with five of five and three of five animals, respectively, in the control group (P = 0.001). Src inhibition by AZM475271 (alone or with gemcitabine) was associated with significantly reduced tumor cell proliferation, decreased tumor microvessel density, and increased apoptosis in vivo. Moreover, these effects were all significantly increased when gemcitabine was combined with AZM475271 compared with gemcitabine alone. CONCLUSIONS: Src inhibition by AZM475271, either alone or in combination with gemcitabine, demonstrated significant antitumor and antimetastatic activity in an orthotopic nude mouse model for human pancreatic cancer. The combination of AZM475271 with gemcitabine sensitized tumor cells to the cytotoxic effect of gemcitabine. [ source: Clin Cancer Res. 2004 Dec 1;10(23):8028-36. ]
Biological target:
AZM475271 is a potent and selective Src kinase inhibitor with IC50 of 5 nM; no inhibitory activity on Flt3, KDR, Tie-2.
In vitro activity:
AZM475271 effectively blocked TGF-β1-induced chemokinesis of Panc-1 cells in a dose-dependent fashion and inhibited the high chemokinetic activity of Panc-1 cells with ectopic expression of a constitutively active ALK5T204D mutant. AZM475271 but not another Src inhibitor, SU6656, partially relieved the suppressive effect of TGF-β1 on E-cadherin and inhibited TGF-β1-induced upregulation of the MMP2, MMP9, N-cadherin and vimentin genes, activity of a TGF-β1-dependent reporter gene, and activation of Smad2 and Smad3.
Reference: Anticancer Agents Med Chem. 2017;17(7):966-972. https://pubmed.ncbi.nlm.nih.gov/27671303/
In vivo activity:
Tumors appeared to be palpable at day 14 after tumor cell injection in all animals except mice treated with both AZM475271 and gemcitabine, in which the earliest possible palpation of the tumors was at day 17 after tumor cell injection. In all treated animals, the median tumor volume was significantly less than that in control mice (AZM475271-treated animals, 827 mm3; gemcitabine-treated animals, 393 mm3; AZM475271 + gemcitabine-treated animals, 124 mm3; control animals, 1359 mm3; Fig. 2; Table 1).
Reference: Clin Cancer Res. 2004 Dec 1;10(23):8028-36. https://pubmed.ncbi.nlm.nih.gov/15585638/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
43.2 |
97.42 |
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
442.94
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. Bartscht T, Rosien B, Rades D, Kaufmann R, Biersack H, Lehnert H, Ungefroren H. TGF-β Signal Transduction in Pancreatic Carcinoma Cells is Sensitive to Inhibition by the Src Tyrosine Kinase Inhibitor AZM475271. Anticancer Agents Med Chem. 2017;17(7):966-972. doi: 10.2174/1871520616666160926110513. PMID: 27671303.
2. Ischenko I, Guba M, Yezhelyev M, Papyan A, Schmid G, Green T, Fennell M, Jauch KW, Bruns CJ. Effect of Src kinase inhibition on metastasis and tumor angiogenesis in human pancreatic cancer. Angiogenesis. 2007;10(3):167-82. doi: 10.1007/s10456-007-9071-3. Epub 2007 May 8. PMID: 17486419.
3. Ischenko I, Seeliger H, Camaj P, Kleespies A, Guba M, Eichhorn ME, Jauch KW, Bruns CJ. Src tyrosine kinase inhibition suppresses lymphangiogenesis in vitro and in vivo. Curr Cancer Drug Targets. 2010 Aug;10(5):546-53. doi: 10.2174/156800910791517181. PMID: 20370688.
4. Yezhelyev MV, Koehl G, Guba M, Brabletz T, Jauch KW, Ryan A, Barge A, Green T, Fennell M, Bruns CJ. Inhibition of SRC tyrosine kinase as treatment for human pancreatic cancer growing orthotopically in nude mice. Clin Cancer Res. 2004 Dec 1;10(23):8028-36. doi: 10.1158/1078-0432.CCR-04-0621. PMID: 15585638.
In vitro protocol:
1. Bartscht T, Rosien B, Rades D, Kaufmann R, Biersack H, Lehnert H, Ungefroren H. TGF-β Signal Transduction in Pancreatic Carcinoma Cells is Sensitive to Inhibition by the Src Tyrosine Kinase Inhibitor AZM475271. Anticancer Agents Med Chem. 2017;17(7):966-972. doi: 10.2174/1871520616666160926110513. PMID: 27671303.
2. Ischenko I, Guba M, Yezhelyev M, Papyan A, Schmid G, Green T, Fennell M, Jauch KW, Bruns CJ. Effect of Src kinase inhibition on metastasis and tumor angiogenesis in human pancreatic cancer. Angiogenesis. 2007;10(3):167-82. doi: 10.1007/s10456-007-9071-3. Epub 2007 May 8. PMID: 17486419.
In vivo protocol:
1. Ischenko I, Seeliger H, Camaj P, Kleespies A, Guba M, Eichhorn ME, Jauch KW, Bruns CJ. Src tyrosine kinase inhibition suppresses lymphangiogenesis in vitro and in vivo. Curr Cancer Drug Targets. 2010 Aug;10(5):546-53. doi: 10.2174/156800910791517181. PMID: 20370688.
2. Yezhelyev MV, Koehl G, Guba M, Brabletz T, Jauch KW, Ryan A, Barge A, Green T, Fennell M, Bruns CJ. Inhibition of SRC tyrosine kinase as treatment for human pancreatic cancer growing orthotopically in nude mice. Clin Cancer Res. 2004 Dec 1;10(23):8028-36. doi: 10.1158/1078-0432.CCR-04-0621. PMID: 15585638.
1: Ischenko I, Seeliger H, Camaj P, Kleespies A, Guba M, Eichhorn ME, Jauch KW, Bruns CJ. Src tyrosine kinase inhibition suppresses lymphangiogenesis in vitro and in vivo. Curr Cancer Drug Targets. 2010 Aug;10(5):546-53. PubMed PMID: 20370688.
2: Ischenko I, Guba M, Yezhelyev M, Papyan A, Schmid G, Green T, Fennell M, Jauch KW, Bruns CJ. Effect of Src kinase inhibition on metastasis and tumor angiogenesis in human pancreatic cancer. Angiogenesis. 2007;10(3):167-82. Epub 2007 May 8. PubMed PMID: 17486419.
3: Yezhelyev MV, Koehl G, Guba M, Brabletz T, Jauch KW, Ryan A, Barge A, Green T, Fennell M, Bruns CJ. Inhibition of SRC tyrosine kinase as treatment for human pancreatic cancer growing orthotopically in nude mice. Clin Cancer Res. 2004 Dec 1;10(23):8028-36. PubMed PMID: 15585638.
