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MedKoo Cat#: 524320 | Name: AZ-23
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Description:

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

AZ-23 is a potent and selective tyrosine kinase (Trk) inhibitor having potential for therapeutic utility in neuroblastoma and multiple other cancers.

Chemical Structure

AZ-23
AZ-23
CAS#915720-21-7

Theoretical Analysis

MedKoo Cat#: 524320

Name: AZ-23

CAS#: 915720-21-7

Chemical Formula: C17H19ClFN7O

Exact Mass: 391.1324

Molecular Weight: 391.83

Elemental Analysis: C, 52.11; H, 4.89; Cl, 9.05; F, 4.85; N, 25.02; O, 4.08

Price and Availability

Size Price Availability Quantity
5mg USD 350.00 2 Weeks
25mg USD 950.00 2 Weeks
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Related CAS #
No Data
Synonym
AZ-23; AZ 23; AZ23; UNII-009OMI967N;
IUPAC/Chemical Name
2,4-Pyrimidinediamine, 5-chloro-N2-((1S)-1-(5-fluoro-2-pyridinyl)ethyl)-N4-(5-(1-methylethoxy)-1H-pyrazol-3-yl)-
InChi Key
LBVKEEFIPBQIMD-JTQLQIEISA-N
InChi Code
InChI=1S/C17H19ClFN7O/c1-9(2)27-15-6-14(25-26-15)23-16-12(18)8-21-17(24-16)22-10(3)13-5-4-11(19)7-20-13/h4-10H,1-3H3,(H3,21,22,23,24,25,26)/t10-/m0/s1
SMILES Code
C[C@@H](c1ccc(cn1)F)Nc2ncc(c(n2)Nc3cc([nH]n3)OC(C)C)Cl
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
Product Data
Product Data
Instruction
View handling instruction
Biological target:
AZ-23 is an ATP-competitive and orally bioavailable Trk kinase A/B/C inhibitor with IC50s of 2 nM (TrkA), 8 nM (TrkB), 24 nM (FGFR1), 52 nM (Flt3), 55 nM (Ret), 84 nM (MuSk), 99 nM (Lck), respectively.
In vitro activity:
As shown in Table 1, AZ-23 was found to potently inhibit Trk-dependent survival in the MCF10A-TrkA-Δ cells (EC50 1.51 nmol/L) with a >1,600-fold window over EGF-driven survival in the parental MCF10A cells (EC50 2,430 nmol/L). A similar selectivity assay was done using the erythroid leukemia TF-1 cell line. TF-1 cells were originally derived from a patient with AML and express endogenous levels of wild-type TrkA. Using this assay, AZ-23 was found to inhibit NGF-mediated survival (EC50 1.01 nmol/L), a result similar to that seen in the engineered MCF10A-TrkA-Δ cells (Table 1). AZ-23 had no effect on GM-CSF driven proliferation at concentrations up to 1 μmol/L. Together, these data suggest that AZ-23 is a potent and selective inhibitor of survival in cell lines whose growth is mediated by activation through the Trk-NGF kinase pathway. Reference: Mol Cancer Ther. 2009 Jul;8(7):1818-27. https://pubmed.ncbi.nlm.nih.gov/19509272/
In vivo activity:
Mice were dosed once or twice daily, by oral gavage, for 4 days at 10 or 50 mg/kg. As seen in Fig. 3B and C, statistically significant, dose-dependent inhibition of tumor growth and growth delay after treatment cessation was observed. All doses/schedules of AZ-23 caused regressions during treatment. At the higher dose level, both schedules caused tumor regressions in >80% of animals and prevented tumor regrowth after the last dose for ∼3 to 4 days. AZ-23 was well tolerated at doses up to 100 mg/kg twice daily for 14 days with minimal body weight loss (<5%) seen during the dosing period in all treatment groups, including vehicle, and no signs of clinical distress. At high doses (50–100 mpk, twice daily), some reversible weight gain was observed. Reference: Mol Cancer Ther. 2009 Jul;8(7):1818-27. https://pubmed.ncbi.nlm.nih.gov/19509272/
Solvent mg/mL mM
Solubility
DMSO 125.0 319.02
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 391.83 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. Thress K, Macintyre T, Wang H, Whitston D, Liu ZY, Hoffmann E, Wang T, Brown JL, Webster K, Omer C, Zage PE, Zeng L, Zweidler-McKay PA. Identification and preclinical characterization of AZ-23, a novel, selective, and orally bioavailable inhibitor of the Trk kinase pathway. Mol Cancer Ther. 2009 Jul;8(7):1818-27. doi: 10.1158/1535-7163.MCT-09-0036. Epub 2009 Jun 9. PMID: 19509272.
In vitro protocol:
1. Thress K, Macintyre T, Wang H, Whitston D, Liu ZY, Hoffmann E, Wang T, Brown JL, Webster K, Omer C, Zage PE, Zeng L, Zweidler-McKay PA. Identification and preclinical characterization of AZ-23, a novel, selective, and orally bioavailable inhibitor of the Trk kinase pathway. Mol Cancer Ther. 2009 Jul;8(7):1818-27. doi: 10.1158/1535-7163.MCT-09-0036. Epub 2009 Jun 9. PMID: 19509272.
In vivo protocol:
1. Thress K, Macintyre T, Wang H, Whitston D, Liu ZY, Hoffmann E, Wang T, Brown JL, Webster K, Omer C, Zage PE, Zeng L, Zweidler-McKay PA. Identification and preclinical characterization of AZ-23, a novel, selective, and orally bioavailable inhibitor of the Trk kinase pathway. Mol Cancer Ther. 2009 Jul;8(7):1818-27. doi: 10.1158/1535-7163.MCT-09-0036. Epub 2009 Jun 9. PMID: 19509272.
1: Wang T, Lamb ML, Block MH, Davies AM, Han Y, Hoffmann E, Ioannidis S, Josey JA, Liu ZY, Lyne PD, MacIntyre T, Mohr PJ, Omer CA, Sjögren T, Thress K, Wang B, Wang H, Yu D, Zhang HJ. Discovery of Disubstituted Imidazo[4,5-b]pyridines and Purines as Potent TrkA Inhibitors. ACS Med Chem Lett. 2012 Jul 26;3(9):705-9. doi: 10.1021/ml300074j. eCollection 2012 Sep 13. PubMed PMID: 24900538; PubMed Central PMCID: PMC4025776. 2: Thress K, Macintyre T, Wang H, Whitston D, Liu ZY, Hoffmann E, Wang T, Brown JL, Webster K, Omer C, Zage PE, Zeng L, Zweidler-McKay PA. Identification and preclinical characterization of AZ-23, a novel, selective, and orally bioavailable inhibitor of the Trk kinase pathway. Mol Cancer Ther. 2009 Jul;8(7):1818-27. doi: 10.1158/1535-7163.MCT-09-0036. Epub 2009 Jun 9. PubMed PMID: 19509272. 3: Wang T, Lamb ML, Scott DA, Wang H, Block MH, Lyne PD, Lee JW, Davies AM, Zhang HJ, Zhu Y, Gu F, Han Y, Wang B, Mohr PJ, Kaus RJ, Josey JA, Hoffmann E, Thress K, Macintyre T, Wang H, Omer CA, Yu D. Identification of 4-aminopyrazolylpyrimidines as potent inhibitors of Trk kinases. J Med Chem. 2008 Aug 14;51(15):4672-84. doi: 10.1021/jm800343j. Epub 2008 Jul 23. PubMed PMID: 18646745.