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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Defactinib (formerly known as VS-6063, PF-04554878) is a selective, ATP-competitive and orally bioactive small molecule inhibitor of the FAK (focal adhesion kinase) with potential antitumor activity. It inhibits the phosphorylation of FAK at the Tyr397 site in a time- and dose-dependent manner. FAK is a nonreceptor tyrosine kinase that plays a vital role in many oncogenic pathways. Increased FAK expression has been reported in a number of tumor types, including breast, colon, and ovarian cancers. Therefore, as an inhibitor of FAK, defactinib has potential antineoplastic activities.
| ln Vitro |
FAK phosphorylation at Tyr397 is inhibited by defactinib (VS-6063) in a dose- and time-dependent manner. Defactinib lowers AKT and YB-1 levels in taxane-resistant cell lines, according to RPPA findings. Defactinib dose-dependently and statistically significantly suppressed the expression of pFAK (Tyr397) in all cell lines. Within three hours, defactinib blocks the expression of pFAK (Tyr397), and within 48 hours, expression progressively returns [1].
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| ln Vivo |
Within three hours, defactinib (VS-6063) at doses of 25 mg/kg twice day or more induced statistically significant suppression of pFAK (Tyr397), and within twenty-four hours, expression was restored. As a result, the dosage schedule for the ensuing treatment trials was determined to be Defactinib at 25 mg/kg twice day. In the course of the treatment trials, four groups of ten female nude mice with intraperitoneal HeyA8 tumors were randomly assigned: 1) oral administration of vehicle twice a day and weekly intraperitoneal injection of phosphate buffered saline (control); 2) Defactinib 25 mg/kg PO twice a day; 3) PTX weekly IP; and 4) VDefactinib 25 mg/kg PO twice a day. The HeyA8 model showed that PTX monotherapy reduced tumor weight by 87.4%, however combination therapy reduced tumor weight by the highest amount, 97.9% (P=0.05 compared with PTX). Tumor weight decreased in the combination therapy group in the SKOV3ip1 model by 92.7% as compared to PTX (P<0.001)[1].
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| Additional Infomation |
Defactinib has been investigated for the treatment of Malignant Pleural Mesothelioma.
Defactinib is an orally bioavailable, small-molecule focal adhesion kinase (FAK) inhibitor with potential antiangiogenic and antineoplastic activities. Defactinib inhibits FAK, which may prevent the integrin-mediated activation of several downstream signal transduction pathways, including those involving RAS/MEK/ERK and PI3K/Akt, thus inhibiting tumor cell migration, proliferation, survival, and tumor angiogenesis. The tyrosine kinase FAK, a signal transducer for integrins, is normally activated by binding to integrins in the extracellular matrix (ECM) but may be upregulated and constitutively activated in various tumor cell types. See also: Defactinib Hydrochloride (annotation moved to). |
| Molecular Formula |
C20H21F3N8O3S
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|---|---|
| Molecular Weight |
510.49
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| Exact Mass |
510.14
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| CAS # |
1073154-85-4
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| Related CAS # |
Defactinib hydrochloride;1073160-26-5
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| PubChem CID |
25117126
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.616
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| LogP |
-0.74
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
35
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| Complexity |
804
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
FWLMVFUGMHIOAA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H21F3N8O3S/c1-24-18(32)12-4-6-13(7-5-12)29-19-28-10-14(20(21,22)23)16(30-19)27-11-15-17(26-9-8-25-15)31(2)35(3,33)34/h4-10H,11H2,1-3H3,(H,24,32)(H2,27,28,29,30)
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| Chemical Name |
N-methyl-4-((4-(((3-(N-methylmethylsulfonamido)pyrazin-2-yl)methyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzamide
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| Synonyms |
VS-6063; PF-04554878; VS6063; VS 6063; PF04554878; PF 04554878; PF4554878;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.90 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.07 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.07 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 5% DMSO+50% PEG 300+5% Tween 80+ddH2O: 5mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9589 mL | 9.7945 mL | 19.5890 mL | |
| 5 mM | 0.3918 mL | 1.9589 mL | 3.9178 mL | |
| 10 mM | 0.1959 mL | 0.9795 mL | 1.9589 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05512208 | Recruiting | Drug: Avutometinib (VS-6766) + defactinib |
Endometrioid Cancer Mucinous Ovarian Cancer |
University of Oklahoma | February 6, 2023 | Phase 2 |
| NCT02913716 | Completed | Drug: defactinib | Healthy Subjects | Verastem, Inc. | August 2015 | Phase 1 |
| NCT03875820 | Active, not recruiting | Drug: VS-6766 Drug: Defactinib |
NSCLC Low Grade Serous Ovarian Cancer |
Institute of Cancer Research, United Kingdom |
December 12, 2017 | Phase 1 |
| NCT04201145 | Withdrawn | Drug: Pembrolizumab Drug: Defactinib |
Malignant Pleural Mesothelioma | Raphael Bueno, MD | September 2020 | Phase 1 |
Y15 and PF-04554878 decreased cell viability in a dose-dependent manner in thyroid cancer cell lines.Oncotarget.2014 Sep 15;5(17):7945-59. |
Y15 and PF-04554878 induced significant gene changes in medullary thyroid cancer TT cells.Oncotarget.2014 Sep 15;5(17):7945-59. |
Y15 and PF-04554878 decreased clonogenicity in a dose-dependent manner in papillary thyroid cancer cell lines.Oncotarget.2014 Sep 15;5(17):7945-59. |
In vitro biological effects of VS-6063 on taxane-sensitive and taxane-resistant cell lines.J Natl Cancer Inst.2013 Oct 2;105(19):1485-95. |
In vivo effects of VS-6063 combined with paclitaxel (PTX).J Natl Cancer Inst.2013 Oct 2;105(19):1485-95. |
VS-6063 restores YB-1–mediated paclitaxel (PTX) resistance.J Natl Cancer Inst.2013 Oct 2;105(19):1485-95. |
VS-6063 downregulated YB-1 phosphorylation and nuclear translocation in taxane-resistant cells by an AKT-dependent pathway.J Natl Cancer Inst.2013 Oct 2;105(19):1485-95. |
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