WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206080
CAS#: 1313725-88-0
Description: Savolitinib, also known as Volitinib, AZD6094 or HMPL-504, is an orally bioavailable inhibitor of the c-Met receptor tyrosine kinase with potential antineoplastic activity. Volitinib selectively binds to and inhibits the activation of c-Met in an ATP-competitive manner, and disrupts c-Met signal transduction pathways. This may result in cell growth inhibition in tumors that overexpress the c-Met protein.
MedKoo Cat#: 206080
Name: Savolitinib
CAS#: 1313725-88-0
Chemical Formula: C17H15N9
Exact Mass: 345.14504
Molecular Weight: 345.36
Elemental Analysis: C, 59.12; H, 4.38; N, 36.50
Synonym: Volitinib; HMPL 504; HMPL0-504; HMPL504; AZD 6094; AZD 6094; AZD-6094; Savolitinib.
IUPAC/Chemical Name: (S)-1-(1-(imidazo[1,2-a]pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazine
InChi Key: XYDNMOZJKOGZLS-NSHDSACASA-N
InChi Code: InChI=1S/C17H15N9/c1-11(12-3-4-15-18-5-6-25(15)10-12)26-17-16(22-23-26)19-8-14(21-17)13-7-20-24(2)9-13/h3-11H,1-2H3/t11-/m0/s1
SMILES Code: CN1N=CC(C2=CN=C3C(N([C@H](C4=CN5C(C=C4)=NC=C5)C)N=N3)=N2)=C1
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: | Savolitinib (AZD-6094) is a c-Met inhibitor with IC50s of 5 nM and 3 nM for c-Met and p-Met, respectively. |
| In vitro activity: | As shown in Table 5, after introduction of a methyl, enantiomerically pure compounds 28 (Savolitinib)–31 demonstrated good inhibition of c-Met activity. Compared with unbranched compounds 16 and 23C, compounds 28 and 30, respectively, had equal activities against c-Met kinase and slightly better potency in cellular assays. More significantly, their abilities to inhibit HGF-induced proliferation were improved. Especially compound 28 inhibited proliferation 12-fold more potently than compound 16. Reference: J Med Chem. 2014 Sep 25;57(18):7577-89. https://pubmed.ncbi.nlm.nih.gov/25148209/ |
| In vivo activity: | AZD6094 dosed at 0.5, 2.5, 10, and 25 mg/kg daily induced dose dependent antitumor activity in RCC-47 resulting in approximately 63% TGI, ∼89% TGI, ∼64% regression, and ∼96% regression, respectively (Fig. 3B). RCC-47 is a fast growing model, with animals in the vehicle group requiring sacrifice as early as 10 days after initiation of treatment. Tumors grew back in 9 of 10 mice within 3 weeks after treatment was stopped; one mouse remained tumor free for 3 months (final measurement, results not shown). In RCC-43b, AZD6094 again showed a dose-dependent antitumor activity ranging from approximately 85% TGI when dosed at 2.5 mg/kg daily, stasis when dosed 10 mg/kg daily, and approximately 20% regression when dosed at 25 mg/kg daily. Reference: Clin Cancer Res. 2015 Jun 15;21(12):2811-9. https://clincancerres.aacrjournals.org/content/21/12/2811.long |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 25.0 | 72.4 |
The following data is based on the product molecular weight 345.36 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. Jia H, Dai G, Weng J, Zhang Z, Wang Q, Zhou F, Jiao L, Cui Y, Ren Y, Fan S, Zhou J, Qing W, Gu Y, Wang J, Sai Y, Su W. Discovery of (S)-1-(1-(Imidazo[1,2-a]pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazine (volitinib) as a highly potent and selective mesenchymal-epithelial transition factor (c-Met) inhibitor in clinical development for treatment of cancer. J Med Chem. 2014 Sep 25;57(18):7577-89. doi: 10.1021/jm500510f. Epub 2014 Sep 15. PMID: 25148209. 2. Hosonuma M, Sakai N, Furuya H, Kurotaki Y, Sato Y, Handa K, Dodo Y, Ishikawa K, Tsubokura Y, Negishi-Koga T, Tsuji M, Kasama T, Kiuchi Y, Takami M, Isozaki T. Inhibition of hepatocyte growth factor/c-Met signalling abrogates joint destruction by suppressing monocyte migration in rheumatoid arthritis. Rheumatology (Oxford). 2021 Jan 5;60(1):408-419. doi: 10.1093/rheumatology/keaa310. PMID: 32770199. 3. Schuller AG, Barry ER, Jones RD, Henry RE, Frigault MM, Beran G, Linsenmayer D, Hattersley M, Smith A, Wilson J, Cairo S, Déas O, Nicolle D, Adam A, Zinda M, Reimer C, Fawell SE, Clark EA, D'Cruz CM. The MET Inhibitor AZD6094 (Savolitinib, HMPL-504) Induces Regression in Papillary Renal Cell Carcinoma Patient-Derived Xenograft Models. Clin Cancer Res. 2015 Jun 15;21(12):2811-9. doi: 10.1158/1078-0432.CCR-14-2685. Epub 2015 Mar 16. PMID: 25779944. |
| In vitro protocol: | 1. Jia H, Dai G, Weng J, Zhang Z, Wang Q, Zhou F, Jiao L, Cui Y, Ren Y, Fan S, Zhou J, Qing W, Gu Y, Wang J, Sai Y, Su W. Discovery of (S)-1-(1-(Imidazo[1,2-a]pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazine (volitinib) as a highly potent and selective mesenchymal-epithelial transition factor (c-Met) inhibitor in clinical development for treatment of cancer. J Med Chem. 2014 Sep 25;57(18):7577-89. doi: 10.1021/jm500510f. Epub 2014 Sep 15. PMID: 25148209. |
| In vivo protocol: | 1. Hosonuma M, Sakai N, Furuya H, Kurotaki Y, Sato Y, Handa K, Dodo Y, Ishikawa K, Tsubokura Y, Negishi-Koga T, Tsuji M, Kasama T, Kiuchi Y, Takami M, Isozaki T. Inhibition of hepatocyte growth factor/c-Met signalling abrogates joint destruction by suppressing monocyte migration in rheumatoid arthritis. Rheumatology (Oxford). 2021 Jan 5;60(1):408-419. doi: 10.1093/rheumatology/keaa310. PMID: 32770199. 2. Schuller AG, Barry ER, Jones RD, Henry RE, Frigault MM, Beran G, Linsenmayer D, Hattersley M, Smith A, Wilson J, Cairo S, Déas O, Nicolle D, Adam A, Zinda M, Reimer C, Fawell SE, Clark EA, D'Cruz CM. The MET Inhibitor AZD6094 (Savolitinib, HMPL-504) Induces Regression in Papillary Renal Cell Carcinoma Patient-Derived Xenograft Models. Clin Cancer Res. 2015 Jun 15;21(12):2811-9. doi: 10.1158/1078-0432.CCR-14-2685. Epub 2015 Mar 16. PMID: 25779944. |
1: Gavine PR, Ren Y, Han L, Lv J, Fan S, Zhang W, Xu W, Liu YJ, Zhang T, Fu H, Yu Y, Wang H, Xu S, Zhou F, Su X, Yin X, Xie L, Wang L, Qing W, Jiao L, Su W, Wang QM. Volitinib, a potent and highly selective c-Met inhibitor, effectively blocks c-Met signaling and growth in c-MET amplified gastric cancer patient-derived tumor xenograft models. Mol Oncol. 2014 Sep 10. pii: S1574-7891(14)00210-5. doi: 10.1016/j.molonc.2014.08.015. [Epub ahead of print] PubMed PMID: 25248999.
2: Jia H, Dai G, Weng J, Zhang Z, Wang Q, Zhou F, Jiao L, Cui Y, Ren Y, Fan S, Zhou J, Qing W, Gu Y, Wang J, Sai Y, Su W. Discovery of (S)-1-(1-(Imidazo[1,2-a]pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2, 3]triazolo[4,5-b]pyrazine (Volitinib) as a Highly Potent and Selective Mesenchymal-Epithelial Transition Factor (c-Met) Inhibitor in Clinical Development for Treatment of Cancer. J Med Chem. 2014 Sep 15. [Epub ahead of print] PubMed PMID: 25148209.
