Savolitinib | Volitinib | HMPL-504 | AZD-6094 | CAS#1313725-88-0 | c-MET inhibitor

MedKoo Cat#: 206080 | Name: Savolitinib

Description:

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

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.

Chemical Structure

Savolitinib

CAS#1313725-88-0

Theoretical Analysis

MedKoo Cat#: 206080

Name: Savolitinib

CAS#: 1313725-88-0

Chemical Formula: C17H15N9

Exact Mass: 345.1450

Molecular Weight: 345.36

Elemental Analysis: C, 59.12; H, 4.38; N, 36.50

Price and Availability

Size	Price	Availability
5mg	USD 110.00	Ready to ship
10mg	USD 180.00	Ready to ship
25mg	USD 385.00	Ready to ship
50mg	USD 650.00	Ready to ship
100mg	USD 1,100.00	Ready to ship

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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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#B7B11C16

QC Data

View QC data: current batch, Lot#B7B11C16

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMSO	25.0	72.40

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 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:

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: Li R, Liu X, Xu Y, Zhao J, Zhong W, Gao X, Chen M, Wang M. Remarkable pathological response to neoadjuvant tepotinib in lung adenocarcinoma with MET exon 14 skipping mutation: A case report. Thorac Cancer. 2024 Sep 29. doi: 10.1111/1759-7714.15459. Epub ahead of print. PMID: 39343987. 2: Yu Y, Guo Q, Zhang Y, Fang J, Zhong D, Liu B, Pan P, Lv D, Wu L, Zhao Y, Li J, Liu Z, Liu C, Su H, Fan Y, Zhang T, Liu A, Jin B, Wang Y, Zhou J, Zhang Z, Ran F, Song X, Shi M, Su W, Lu S; study group. Savolitinib in patients in China with locally advanced or metastatic treatment-naive non-small-cell lung cancer harbouring MET exon 14 skipping mutations: results from a single-arm, multicohort, multicentre, open-label, phase 3b confirmatory study. Lancet Respir Med. 2024 Sep 10:S2213-2600(24)00211-X. doi: 10.1016/S2213-2600(24)00211-X. Epub ahead of print. PMID: 39270695. 3: Mitsudomi T. Savolitinib in NSCLC: progress in the MET exon 14 journey. Lancet Respir Med. 2024 Sep 10:S2213-2600(24)00258-3. doi: 10.1016/S2213-2600(24)00258-3. Epub ahead of print. PMID: 39270694. 4: Barata P, Tangen C, Plets M, Thompson IM Jr, Narayan V, George DJ, Heng DYC, Shuch B, Stein M, Gulati S, Tretiakova M, Tripathi A, Bjarnason GA, Humphrey P, Adeniran A, Vaishampayan U, Alva A, Zhang T, Cole S, Lara PN Jr, Lerner SP, Balzer-Haas N, Pal SK. Final Overall Survival Analysis of S1500: A Randomized, Phase II Study Comparing Sunitinib With Cabozantinib, Crizotinib, and Savolitinib in Advanced Papillary Renal Cell Carcinoma. J Clin Oncol. 2024 Sep 10:JCO2400767. doi: 10.1200/JCO.24.00767. Epub ahead of print. PMID: 39255440. 5: Deng R, Li YY, Bai LL, Zhou L, Wang YS. Case report: A case of Savolitinib in the treatment of MET amplification mutation advanced lung adenocarcinoma with rare bilateral breast metastasis. Front Oncol. 2024 Aug 13;14:1450855. doi: 10.3389/fonc.2024.1450855. PMID: 39193383; PMCID: PMC11347308. 6: Li X, Lu Y, Zhao J, Yu Y, Tian H, Zhu H, Li W, Xia Y, Chen L. Savolitinib conferred sensitivity in a patient with D1228H mutation-induced capmatinib- resistant MET exon 14 skipping mutated lung adenocarcinoma. J Cancer Res Clin Oncol. 2024 Aug 24;150(8):395. doi: 10.1007/s00432-024-05920-1. PMID: 39180576; PMCID: PMC11344724. 7: Gu F, Yang P, Li L, Li C. Drug-induced liver injury associated with savolitinib: a novel case report and causality assessment. BMC Pulm Med. 2024 Aug 9;24(1):384. doi: 10.1186/s12890-024-03201-8. PMID: 39123181; PMCID: PMC11316428. 8: Meng Y, Zhou W, Li C, Zhou X, Li X, Li L, Fu Q, Huang J, Yue Y, Shen X, Yang L, Wang M. Case report: Response to tepotinib in Chinese non-small cell lung cancer patients harboring METex14 skipping with varying features. Front Oncol. 2024 Jul 2;14:1383964. doi: 10.3389/fonc.2024.1383964. PMID: 39015492; PMCID: PMC11250067. 9: Tripathi A, Tangen CM, Plets M, Li X, Tretiakova M, Humphrey PA, Adeniran A, Barata PC, Gulati S, Bergerot CD, Pruthi DK, Thompson IM, Lara PN Jr, Lerner SP, Pal SK, Shuch BM. Pathological concordance rate and outcomes by subtype in advanced papillary renal cell carcinoma. BJU Int. 2024 Oct;134(4):596-601. doi: 10.1111/bju.16403. Epub 2024 Jul 16. PMID: 39014969. 10: Shen L, Zhao J, Yang Y, Mu S, Yu Y, Han Y, Lu S. Prominent response to savolitinib monotherapy in high-grade fetal adenocarcinoma with MET amplification and concurrent brain metastasis: a case report. Transl Lung Cancer Res. 2024 Jun 30;13(6):1407-1413. doi: 10.21037/tlcr-24-124. Epub 2024 Jun 25. PMID: 38973955; PMCID: PMC11225042. 11: Kowalski DM, Zaborowska-Szmit M, Szmit S, Jaśkiewicz P, Krzakowski M. The combination of osimertinib and savolitinib as molecular inhibition of EGFR and MET receptors may be selected to provide maximum effectiveness and acceptable toxicity. Transl Lung Cancer Res. 2024 Jun 30;13(6):1426-1431. doi: 10.21037/tlcr-24-204. Epub 2024 Jun 25. PMID: 38973950; PMCID: PMC11225044. 12: Wang R, Liu Y, Yu X, Wang W, Liu J. Joint DNA-RNA-based NGS for diagnosis and treatment of a rare CD47-MET fusion lung adenocarcinoma which was immunoresistant and savoltinib-sensitive: a case report. Front Immunol. 2024 Jun 18;15:1386561. doi: 10.3389/fimmu.2024.1386561. PMID: 38957460; PMCID: PMC11217332. 13: Kim JS, Kim MY, Hong S. Characterization of MET Alterations in 37 Gastroesophageal Cancer Cell Lines for MET-Targeted Therapy. Int J Mol Sci. 2024 May 29;25(11):5975. doi: 10.3390/ijms25115975. PMID: 38892160; PMCID: PMC11173193. 14: Wang Z, Niu D. To explore the prognostic characteristics of colon cancer based on tertiary lymphoid structure-related genes and reveal the characteristics of tumor microenvironment and drug prediction. Sci Rep. 2024 Jun 12;14(1):13555. doi: 10.1038/s41598-024-64308-w. PMID: 38867070; PMCID: PMC11169531. 15: Sun X, Li J, Gao X, Huang Y, Pang Z, Lv L, Li H, Liu H, Zhu L. Disulfidptosis‑related lncRNA prognosis model to predict survival therapeutic response prediction in lung adenocarcinoma. Oncol Lett. 2024 May 29;28(2):342. doi: 10.3892/ol.2024.14476. PMID: 38855504; PMCID: PMC11157670. 16: Weng ZY, Huang WY, Shi BK, Pan JJ. Role of savolitinib in advanced gastric adenocarcinoma with meningeal carcinomatosis and cerebellar metastasis: A case report. World J Clin Cases. 2024 May 26;12(15):2636-2641. doi: 10.12998/wjcc.v12.i15.2636. PMID: 38817213; PMCID: PMC11135453. 17: Zhang Y, Shen L, Peng Z. Advances in MET tyrosine kinase inhibitors in gastric cancer. Cancer Biol Med. 2024 May 10;21(6):484–98. doi: 10.20892/j.issn.2095-3941.2024.0044. PMID: 38727001; PMCID: PMC11208904. 18: Wei Y, Wang L, Jin Z, Jia Q, Brcic L, Akaba T, Chu Q. Biological characteristics and clinical treatment of pulmonary sarcomatoid carcinoma: a narrative review. Transl Lung Cancer Res. 2024 Mar 29;13(3):635-653. doi: 10.21037/tlcr-24-127. Epub 2024 Mar 27. PMID: 38601447; PMCID: PMC11002509. 19: Wang Y, Bu Y, Che G. Savolitinib as a novel treatment regimen for pulmonary sarcomatoid carcinoma with MET exon 14 skipping mutation. Asian J Surg. 2024 Jul;47(7):3308-3309. doi: 10.1016/j.asjsur.2024.03.165. Epub 2024 Apr 10. PMID: 38599970. 20: Symons JE, Hall C, McCabe JF, Hall SR. Morphological Control of Crystalline Savolitinib via the Volatile Deep Eutectic Solvent Technique. Cryst Growth Des. 2024 Mar 1;24(6):2567-2572. doi: 10.1021/acs.cgd.4c00035. PMID: 38525101; PMCID: PMC10958444.