WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H206606
CAS#: 1190836-34-0 (free base)
Description: TAS-115, also known as Pamufetinib, is a c-MET Inhibitor. TAS-115 inhibited the kinase activity of both VEGFR2 and MET and their signal-dependent cell growth as strongly as other known VEGFR or MET inhibitors. TAS-115 is extremely selective and specific, at least in vitro. In in vivo studies, TAS-115 completely suppressed the progression of MET-inactivated tumor by blocking angiogenesis without toxicity when given every day for 6 weeks, even at a serum-saturating dose of TAS-115. TAS-115 induced marked tumor shrinkage and prolonged survival in MET-amplified human cancer-bearing mice. TAS-115 is a unique VEGFR/MET-targeted inhibitor with improved antitumor efficacy and decreased toxicity.
Hodoodo Cat#: H206606
Name: TAS-115 free base
CAS#: 1190836-34-0 (free base)
Chemical Formula: C27H23FN4O4S
Exact Mass: 518.14
Molecular Weight: 518.563
Elemental Analysis: C, 62.54; H, 4.47; F, 3.66; N, 10.80; O, 12.34; S, 6.18
Related CAS #: 1688673-09-7 (mesylate) 1190836-34-0 (free base)
Synonym: TAS-115, TAS 115, TAS115; Pamufetinib
IUPAC/Chemical Name: 4-(2-fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)-7-methoxy-N-methylquinoline-6-carboxamide
InChi Key: ORRNXRYWGDUDOG-UHFFFAOYSA-N
InChi Code: InChI=1S/C27H23FN4O4S/c1-29-26(34)19-14-18-21(15-24(19)35-2)30-11-10-22(18)36-23-9-8-17(13-20(23)28)31-27(37)32-25(33)12-16-6-4-3-5-7-16/h3-11,13-15H,12H2,1-2H3,(H,29,34)(H2,31,32,33,37)
SMILES Code: O=C(NC(NC1=CC(F)=C(OC2=C(C=C(C(NC)=O)C(OC)=C3)C3=NC=C2)C=C1)=S)CC4=CC=CC=C4
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:
| Biological target: | Pamufetinib (TAS-115) is a potent VEGFR and hepatocyte growth factor receptor (c-Met/HGFR)-targeted kinase inhibitor with IC50s of 30 and 32 nM for rVEGFR2 and rMET, respectively. |
| In vitro activity: | Based on the results of the histological analysis, the effect of TAS-115 on osteoclast differentiation was investigated in in vitro studies. The inhibitory potency of TAS-115 towards osteoclast differentiation was evaluated by analysis of TRAP activity in cells after RANKL and M-CSF stimulation. TAS-115 dose-dependently suppressed osteoclast differentiation induced by RANKL and M-CSF, and potently inhibited mouse osteoclast formation at a concentration of 0.3 μM. These data revealed that TAS-115 had the potential to affect RANKL or M-CSF-related signaling pathways in mouse osteoclast formation. To confirm the inhibitory activity of TAS-115 towards human FMS, the cellular IC50 value of TAS-115 against M-CSF-induced FMS phosphorylation in human acute monocytic THP-1 leukemia cells was determined. The IC50 value of TAS-115 was 0.012 μM, and no species differences were observed between mouse and human in the inhibitory activity of TAS-115 for FMS. These results suggested that VEGF, HGF, and M-CSF in the bone lesion activated their respective receptor expressed in osteoclasts, and that TAS-115 blocked the lytic activity and survival of osteoclasts through inhibition of VEGFRs/MET/FMS-related signaling pathways. Reference: PLoS One. 2016 Oct 13;11(10):e0164830. https://pubmed.ncbi.nlm.nih.gov/?term=TAS-115 |
| In vivo activity: | The antitumor efficacy of TAS-115 against MET-amplified human cancer implanted models was evaluated. When MKN45 tumor-bearing nude mice were orally treated with TAS-115 for 14 consecutive days, the TGI value was 76% at a dose of 12.5 mg/kg/d (P < 0.001). TAS-115 at a dose of 50 mg/kg/d completely prevented tumor growth during the treatment period. TAS-115 at a dose of 200 mg/kg/d induced a 48% regression from the initial tumor volume. The estimated 50% effective dose (ED50; the dose at which the TGI value was 50%) of TAS-115 in this model was 8 mg/kg/d. TAS-115 markedly inhibited the phosphorylation of MET and signal transduction factors located downstream from MET (i.e., ERK and AKT) at a dose of 3.1 mg/kg. Reference: Mol Cancer Ther. 2013 Dec;12(12):2685-96. https://pubmed.ncbi.nlm.nih.gov/24140932/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 10.0 | 19.28 |
The following data is based on the product molecular weight 518.56 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. Koyama K, Goto H, Morizumi S, Kagawa K, Nishimura H, Sato S, Kawano H, Toyoda Y, Ogawa H, Homma S, Nishioka Y. The Tyrosine Kinase Inhibitor TAS-115 Attenuates Bleomycin-induced Lung Fibrosis in Mice. Am J Respir Cell Mol Biol. 2019 Apr;60(4):478-487. doi: 10.1165/rcmb.2018-0098OC. PMID: 30540913. 2. Fujita H, Gomori A, Fujioka Y, Kataoka Y, Tanaka K, Hashimoto A, Suzuki T, Ito K, Haruma T, Yamamoto-Yokoi H, Harada N, Sakuragi M, Oda N, Matsuo K, Inada M, Yonekura K. High Potency VEGFRs/MET/FMS Triple Blockade by TAS-115 Concomitantly Suppresses Tumor Progression and Bone Destruction in Tumor-Induced Bone Disease Model with Lung Carcinoma Cells. PLoS One. 2016 Oct 13;11(10):e0164830. doi: 10.1371/journal.pone.0164830. PMID: 27736957; PMCID: PMC5063576. 3.Fujita H, Miyadera K, Kato M, Fujioka Y, Ochiiwa H, Huang J, Ito K, Aoyagi Y, Takenaka T, Suzuki T, Ito S, Hashimoto A, Suefuji T, Egami K, Kazuno H, Suda Y, Nishio K, Yonekura K. The novel VEGF receptor/MET-targeted kinase inhibitor TAS-115 has marked in vivo antitumor properties and a favorable tolerability profile. Mol Cancer Ther. 2013 Dec;12(12):2685-96. doi: 10.1158/1535-7163.MCT-13-0459. Epub 2013 Oct 18. PMID: 24140932. |
| In vitro protocol: | 1. Koyama K, Goto H, Morizumi S, Kagawa K, Nishimura H, Sato S, Kawano H, Toyoda Y, Ogawa H, Homma S, Nishioka Y. The Tyrosine Kinase Inhibitor TAS-115 Attenuates Bleomycin-induced Lung Fibrosis in Mice. Am J Respir Cell Mol Biol. 2019 Apr;60(4):478-487. doi: 10.1165/rcmb.2018-0098OC. PMID: 30540913. 2. Fujita H, Gomori A, Fujioka Y, Kataoka Y, Tanaka K, Hashimoto A, Suzuki T, Ito K, Haruma T, Yamamoto-Yokoi H, Harada N, Sakuragi M, Oda N, Matsuo K, Inada M, Yonekura K. High Potency VEGFRs/MET/FMS Triple Blockade by TAS-115 Concomitantly Suppresses Tumor Progression and Bone Destruction in Tumor-Induced Bone Disease Model with Lung Carcinoma Cells. PLoS One. 2016 Oct 13;11(10):e0164830. doi: 10.1371/journal.pone.0164830. PMID: 27736957; PMCID: PMC5063576. |
| In vivo protocol: | 1. Koyama K, Goto H, Morizumi S, Kagawa K, Nishimura H, Sato S, Kawano H, Toyoda Y, Ogawa H, Homma S, Nishioka Y. The Tyrosine Kinase Inhibitor TAS-115 Attenuates Bleomycin-induced Lung Fibrosis in Mice. Am J Respir Cell Mol Biol. 2019 Apr;60(4):478-487. doi: 10.1165/rcmb.2018-0098OC. PMID: 30540913. 2. Fujita H, Miyadera K, Kato M, Fujioka Y, Ochiiwa H, Huang J, Ito K, Aoyagi Y, Takenaka T, Suzuki T, Ito S, Hashimoto A, Suefuji T, Egami K, Kazuno H, Suda Y, Nishio K, Yonekura K. The novel VEGF receptor/MET-targeted kinase inhibitor TAS-115 has marked in vivo antitumor properties and a favorable tolerability profile. Mol Cancer Ther. 2013 Dec;12(12):2685-96. doi: 10.1158/1535-7163.MCT-13-0459. Epub 2013 Oct 18. PMID: 24140932. |
1: Koyama K, Goto H, Morizumi S, Kagawa K, Nishimura H, Sato S, Kawano H, Toyoda Y, Ogawa H, Homma S, Nishioka Y. The Tyrosine Kinase Inhibitor TAS-115 Attenuates Bleomycin-induced Lung Fibrosis in Mice. Am J Respir Cell Mol Biol. 2019 Apr;60(4):478-487. doi: 10.1165/rcmb.2018-0098OC. PubMed PMID: 30540913.
2: Yamada S, Imura Y, Nakai T, Nakai S, Yasuda N, Kaneko K, Outani H, Takenaka S, Hamada K, Myoui A, Araki N, Ueda T, Itoh K, Yoshikawa H, Naka N. Therapeutic potential of TAS-115 via c-MET and PDGFRα signal inhibition for synovial sarcoma. BMC Cancer. 2017 May 16;17(1):334. doi: 10.1186/s12885-017-3324-3. PubMed PMID: 28511645; PubMed Central PMCID: PMC5434537.
3: Fujita H, Gomori A, Fujioka Y, Kataoka Y, Tanaka K, Hashimoto A, Suzuki T, Ito K, Haruma T, Yamamoto-Yokoi H, Harada N, Sakuragi M, Oda N, Matsuo K, Inada M, Yonekura K. High Potency VEGFRs/MET/FMS Triple Blockade by TAS-115 Concomitantly Suppresses Tumor Progression and Bone Destruction in Tumor-Induced Bone Disease Model with Lung Carcinoma Cells. PLoS One. 2016 Oct 13;11(10):e0164830. doi: 10.1371/journal.pone.0164830. eCollection 2016. PubMed PMID: 27736957; PubMed Central PMCID: PMC5063576.
4: Watanabe K, Hirata M, Tominari T, Matsumoto C, Fujita H, Yonekura K, Murphy G, Nagase H, Miyaura C, Inada M. The MET/Vascular Endothelial Growth Factor Receptor (VEGFR)-targeted Tyrosine Kinase Inhibitor Also Attenuates FMS-dependent Osteoclast Differentiation and Bone Destruction Induced by Prostate Cancer. J Biol Chem. 2016 Sep 30;291(40):20891-20899. Epub 2016 Aug 18. PubMed PMID: 27539855; PubMed Central PMCID: PMC5076502.
5: Kunii E, Ozasa H, Oguri T, Maeno K, Fukuda S, Uemura T, Takakuwa O, Ohkubo H, Takemura M, Niimi A. Reversal of c-MET-mediated Resistance to Cytotoxic Anticancer Drugs by a Novel c-MET Inhibitor TAS-115. Anticancer Res. 2015 Oct;35(10):5241-7. PubMed PMID: 26408683.
6: Nakade J, Takeuchi S, Nakagawa T, Ishikawa D, Sano T, Nanjo S, Yamada T, Ebi H, Zhao L, Yasumoto K, Matsumoto K, Yonekura K, Yano S. Triple inhibition of EGFR, Met, and VEGF suppresses regrowth of HGF-triggered, erlotinib-resistant lung cancer harboring an EGFR mutation. J Thorac Oncol. 2014 Jun;9(6):775-83. doi: 10.1097/JTO.0000000000000170. PubMed PMID: 24828661; PubMed Central PMCID: PMC4132034.
7: Fujita H, Miyadera K, Kato M, Fujioka Y, Ochiiwa H, Huang J, Ito K, Aoyagi Y, Takenaka T, Suzuki T, Ito S, Hashimoto A, Suefuji T, Egami K, Kazuno H, Suda Y, Nishio K, Yonekura K. The novel VEGF receptor/MET-targeted kinase inhibitor TAS-115 has marked in vivo antitumor properties and a favorable tolerability profile. Mol Cancer Ther. 2013 Dec;12(12):2685-96. doi: 10.1158/1535-7163.MCT-13-0459. Epub 2013 Oct 18. PubMed PMID: 24140932.
8: Zhao L, Yasumoto K, Kawashima A, Nakagawa T, Takeuchi S, Yamada T, Matsumoto K, Yonekura K, Yoshie O, Yano S. Paracrine activation of MET promotes peritoneal carcinomatosis in scirrhous gastric cancer. Cancer Sci. 2013 Dec;104(12):1640-6. doi: 10.1111/cas.12301. Epub 2013 Nov 13. PubMed PMID: 24118504.
9: Utsugi T. New challenges and inspired answers for anticancer drug discovery and development. Jpn J Clin Oncol. 2013 Oct;43(10):945-53. doi: 10.1093/jjco/hyt131. Epub 2013 Sep 5. PubMed PMID: 24014883; PubMed Central PMCID: PMC3787805.
10: Belleville I, Vaillant G, Farnier M, Brun JM. [Influence of acute hyperinsulinism on arterial pressure of diabetics. Reproducibility of the hypotensive effect]. Arch Mal Coeur Vaiss. 1988 Jun;81 Spec No:79-82. French. PubMed PMID: 3142434.
