WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200298
CAS#: 848942-61-0 (free bade)
Description: Sapitinib, also known as AZD-8931, is an erbB receptor tyrosine kinase inhibitor with potential antineoplastic activity. erbB kinase inhibitor AZD8931 binds to and inhibits erbB tyrosine receptor kinases, which may result in the inhibition of cellular proliferation and angiogenesis in tumors expressing erbB. The erbB protein family, also called the epidermal growth factor receptor (EGFR) family, plays major roles in tumor cell proliferation and tumor vascularization.
MedKoo Cat#: 200298
Name: Sapitinib free base
CAS#: 848942-61-0 (free bade)
Chemical Formula: C23H25ClFN5O3
Exact Mass: 473.163
Molecular Weight: 473.93
Elemental Analysis: C, 58.29; H, 5.32; Cl, 7.48; F, 4.01; N, 14.78; O, 10.13
Related CAS #: 848942-61-0 (free bade) 1196531-39-1 (fumurate)
Synonym: AZD8931; AZD8931; AZD 8931; Sapitinib
IUPAC/Chemical Name: 2-(4-((4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)-N-methylacetamide
InChi Key: DFJSJLGUIXFDJP-UHFFFAOYSA-N
InChi Code: InChI=1S/C23H25ClFN5O3/c1-26-21(31)12-30-8-6-14(7-9-30)33-20-10-15-18(11-19(20)32-2)27-13-28-23(15)29-17-5-3-4-16(24)22(17)25/h3-5,10-11,13-14H,6-9,12H2,1-2H3,(H,26,31)(H,27,28,29)
SMILES Code: O=C(NC)CN1CCC(OC2=CC3=C(NC4=CC=CC(Cl)=C4F)N=CN=C3C=C2OC)CC1
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
| Biological target: | Sapitinib (AZD-8931) is a reversible, ATP competitive EGFR inhibitor of with IC50s of 4, 3 and 4 nM for EGFR, ErbB2 and ErbB3 in cells, respectively. |
| In vitro activity: | The effects of blocking HER3 on CRC tumor growth were further determined by the subQ xenograft tumor model with treatment of the HER3 inhibitor AZD8931. After HCP-1 cells were injected subQ in the mixture of CM and Matrigel as described above, mice were then treated with either vehicle or AZD8931 by gavage and the tumor growth was monitored over time (Fig. 6). These results showed that LPEC-1 CM treated tumors led to significantly greater tumor growth, as expected. More importantly, AZD8931 significantly inhibited the tumor growth in both CRC CM and LPEC-1 CM-treated CRC tumors compared with tumors without AZD8931 treatment (Fig. 6B). In addition, CRC tumors that were treated by AZD8931 had significantly lower tumor weight compared with tumors not treated with AZD8931, leading to ~2-fold decrease compared to CRC CM treated tumors, and > 4-fold decrease compared to LPEC-1 CM treated tumors (Fig. 6C). Reference: Mol Cancer Res. 2019 Jan; 17(1): 20–29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318043/ |
| In vivo activity: | When tumors reached 40–50 mm3 (~ 16 days), mice were treated daily with AZD8931 (50 mg/kg) or diluent by oral gavage. As shown in Fig. 3a, treatment with AZD8931 rapidly halts B4B8 tumor progression and causes significant shrinkage of tumors (Fig. 3b) compared to tumor-bearing mice treated with diluent as a control. Thus, B4B8 cells serve as a murine HNSCC model to explore EGFR/ERBB-dependent growth in an in vivo setting. Reference: J Transl Med. 2021; 19: 43. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825244/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 33.0 | 69.6 | |
| DMSO | 25.0 | 52.8 |
The following data is based on the product molecular weight 473.93 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 R, Bhattacharya R, Ye X, Fan F, Boulbes DR, Ellis LM. Endothelial Cells Promote Colorectal Cancer Cell Survival by Activating the HER3-AKT Pathway in a Paracrine Fashion. Mol Cancer Res. 2019 Jan;17(1):20-29. doi: 10.1158/1541-7786.MCR-18-0341. Epub 2018 Aug 21. PMID: 30131447; PMCID: PMC6318043. 2. Barlaam B, Anderton J, Ballard P, Bradbury RH, Hennequin LF, Hickinson DM, Kettle JG, Kirk G, Klinowska T, Lambert-van der Brempt C, Trigwell C, Vincent J, Ogilvie D. Discovery of AZD8931, an Equipotent, Reversible Inhibitor of Signaling by EGFR, HER2, and HER3 Receptors. ACS Med Chem Lett. 2013 May 31;4(8):742-6. doi: 10.1021/ml400146c. PMID: 24900741; PMCID: PMC4027407. 3. Korpela SP, Hinz TK, Oweida A, Kim J, Calhoun J, Ferris R, Nemenoff RA, Karam SD, Clambey ET, Heasley LE. Role of epidermal growth factor receptor inhibitor-induced interferon pathway signaling in the head and neck squamous cell carcinoma therapeutic response. J Transl Med. 2021 Jan 23;19(1):43. doi: 10.1186/s12967-021-02706-8. PMID: 33485341; PMCID: PMC7825244. 4. Mu Z, Klinowska T, Dong X, Foster E, Womack C, Fernandez SV, Cristofanilli M. AZD8931, an equipotent, reversible inhibitor of signaling by epidermal growth factor receptor (EGFR), HER2, and HER3: preclinical activity in HER2 non-amplified inflammatory breast cancer models. J Exp Clin Cancer Res. 2014 May 30;33(1):47. doi: 10.1186/1756-9966-33-47. PMID: 24886365; PMCID: PMC4061513. |
| In vitro protocol: | 1. Wang R, Bhattacharya R, Ye X, Fan F, Boulbes DR, Ellis LM. Endothelial Cells Promote Colorectal Cancer Cell Survival by Activating the HER3-AKT Pathway in a Paracrine Fashion. Mol Cancer Res. 2019 Jan;17(1):20-29. doi: 10.1158/1541-7786.MCR-18-0341. Epub 2018 Aug 21. PMID: 30131447; PMCID: PMC6318043. 2. Barlaam B, Anderton J, Ballard P, Bradbury RH, Hennequin LF, Hickinson DM, Kettle JG, Kirk G, Klinowska T, Lambert-van der Brempt C, Trigwell C, Vincent J, Ogilvie D. Discovery of AZD8931, an Equipotent, Reversible Inhibitor of Signaling by EGFR, HER2, and HER3 Receptors. ACS Med Chem Lett. 2013 May 31;4(8):742-6. doi: 10.1021/ml400146c. PMID: 24900741; PMCID: PMC4027407. |
| In vivo protocol: | 1. Korpela SP, Hinz TK, Oweida A, Kim J, Calhoun J, Ferris R, Nemenoff RA, Karam SD, Clambey ET, Heasley LE. Role of epidermal growth factor receptor inhibitor-induced interferon pathway signaling in the head and neck squamous cell carcinoma therapeutic response. J Transl Med. 2021 Jan 23;19(1):43. doi: 10.1186/s12967-021-02706-8. PMID: 33485341; PMCID: PMC7825244. 2. Mu Z, Klinowska T, Dong X, Foster E, Womack C, Fernandez SV, Cristofanilli M. AZD8931, an equipotent, reversible inhibitor of signaling by epidermal growth factor receptor (EGFR), HER2, and HER3: preclinical activity in HER2 non-amplified inflammatory breast cancer models. J Exp Clin Cancer Res. 2014 May 30;33(1):47. doi: 10.1186/1756-9966-33-47. PMID: 24886365; PMCID: PMC4061513. |
1: Mu Z, Klinowska T, Dong X, Foster E, Womack C, Fernandez SV, Cristofanilli M. AZD8931, an equipotent, reversible inhibitor of signaling by epidermal growth factor receptor (EGFR), HER2, and HER3: preclinical activity in HER2 non-amplified inflammatory breast cancer models. J Exp Clin Cancer Res. 2014 May 30;33:47. doi: 10.1186/1756-9966-33-47. PubMed PMID: 24886365; PubMed Central PMCID: PMC4061513.
2: Singleton KR, Kim J, Hinz TK, Marek LA, Casás-Selves M, Hatheway C, Tan AC, DeGregori J, Heasley LE. A receptor tyrosine kinase network composed of fibroblast growth factor receptors, epidermal growth factor receptor, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, and hepatocyte growth factor receptor drives growth and survival of head and neck squamous carcinoma cell lines. Mol Pharmacol. 2013 Apr;83(4):882-93. doi: 10.1124/mol.112.084111. Epub 2013 Jan 31. PubMed PMID: 23371912; PubMed Central PMCID: PMC3608435.
3: Hickinson DM, Klinowska T, Speake G, Vincent J, Trigwell C, Anderton J, Beck S, Marshall G, Davenport S, Callis R, Mills E, Grosios K, Smith P, Barlaam B, Wilkinson RW, Ogilvie D. AZD8931, an equipotent, reversible inhibitor of signaling by epidermal growth factor receptor, ERBB2 (HER2), and ERBB3: a unique agent for simultaneous ERBB receptor blockade in cancer. Clin Cancer Res. 2010 Feb 15;16(4):1159-69. doi: 10.1158/1078-0432.CCR-09-2353. Epub 2010 Feb 9. PubMed PMID: 20145185.
