Name: Defactinib
Brand: BOC Sciences
Price: 399 USD
Availability: MadeToOrder

Purity

>98%

Appearance

White Solid Powder

IUPACName

N-methyl-4-[[4-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide

Synonyms

N-methyl-4-((4-(((3-(N-methylmethylsulfonamido)pyrazin-2-yl)methyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzamide; VS6063; VS 6063; VS-6063; PF04554878; PF-04554878; PF 04554878; PF4554878; PF-4554878

InChI Key

FWLMVFUGMHIOAA-UHFFFAOYSA-N

InChI

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)

Canonical SMILES

CNC(=O)C1=CC=C(C=C1)NC2=NC=C(C(=N2)NCC3=NC=CN=C3N(C)S(=O)(=O)C)C(F)(F)F

1.Identification of Bone-Derived Factors Conferring De Novo Therapeutic Resistance in Metastatic Prostate Cancer.

Lee YC1, Lin SC1, Yu G1, Cheng CJ2, Liu B3, Liu HC1, Hawke DH1, Parikh NU4, Varkaris A4, Corn P4, Logothetis C4, Satcher RL5, Yu-Lee LY6, Gallick GE7, Lin SH8. Cancer Res. 2015 Nov 15;75(22):4949-59. doi: 10.1158/0008-5472.CAN-15-1215. Epub 2015 Nov 3.

Resistance to currently available targeted therapies significantly hampers the survival of patients with prostate cancer with bone metastasis. Here we demonstrate an important resistance mechanism initiated from tumor-induced bone. Studies using an osteogenic patient-derived xenograft, MDA-PCa-118b, revealed that tumor cells resistant to cabozantinib, a Met and VEGFR-2 inhibitor, reside in a "resistance niche" adjacent to prostate cancer-induced bone. We performed secretome analysis of the conditioned medium from tumor-induced bone to identify proteins (termed "osteocrines") found within this resistance niche. In accordance with previous reports demonstrating that activation of integrin signaling pathways confers therapeutic resistance, 27 of the 90 osteocrines identified were integrin ligands. We found that following cabozantinib treatment, only tumor cells positioned adjacent to the newly formed woven bone remained viable and expressed high levels of pFAK-Y397 and pTalin-S425, mediators of integrin signaling.

2.A first-in-Asian phase 1 study to evaluate safety, pharmacokinetics and clinical activity of VS-6063, a focal adhesion kinase (FAK) inhibitor in Japanese patients with advanced solid tumors.

Shimizu T1, Fukuoka K2, Takeda M2, Iwasa T2, Yoshida T2, Horobin J3, Keegan M3, Vaickus L3, Chavan A3, Padval M3, Nakagawa K2. Cancer Chemother Pharmacol. 2016 May;77(5):997-1003. doi: 10.1007/s00280-016-3010-1. Epub 2016 Mar 30.

PURPOSE: VS-6063 (also known as defactinib or PF-04554878) is a second-generation inhibitor of focal adhesion kinase and proline-rich tyrosine kinase-2. This phase 1 study evaluated the safety and tolerability, pharmacokinetics, and clinical activity of VS-6063 in Japanese subjects with advanced solid tumor malignancies in a first-in-Asian study setting.

3.A phase I study of VS-6063, a second-generation focal adhesion kinase inhibitor, in patients with advanced solid tumors.

Jones SF1, Siu LL2, Bendell JC3, Cleary JM4, Razak AR2, Infante JR3, Pandya SS5, Bedard PL2, Pierce KJ6, Houk B7, Roberts WG6, Shreeve SM7, Shapiro GI8. Invest New Drugs. 2015 Oct;33(5):1100-7. doi: 10.1007/s10637-015-0282-y. Epub 2015 Sep 4.

OBJECTIVE: VS-6063 (also known as defactinib or PF-04554878) is a second-generation inhibitor of focal adhesion kinase (FAK) and proline-rich tyrosine kinase-2 (Pyk2). This phase I dose-escalation study was conducted in patients with advanced solid malignancies.

ConcentrationVolumeMass	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	-	-	-
50 mM	-	-	-

HNMR

HPLC

Is there synergy between Defactinib and paclitaxel in paclitaxel-like sensitive (SKOV3ip1) and paclitaxel-like resistant (SKOV3-TR) cell lines ?

The combination of Defactinib and paclitaxel synergistically decreased proliferation and increased apoptosis of SKOV3ip1, SKOV3-TR, HeyA8, and HeyA8-MDR cells in paclitaxel-sensitive (SKOV3ip1) and paclitaxel-resistant (SKOV3-TR) cell lines.

3/1/2016

Does Defactinib inhibit the cellular activity of thyroid cancer cells ? If so, does it synergize with Y15 in thyroid cancer cell lines ?

Defactinib can inhibit viability in thyroid cancer cell lines, and Defactinib and Y15 synergistically work together to reduce viability, clonogenicity, and cell attachment in thyroid cancer cell lines.

30/8/2021

We plan to administer Defactinib intraperitoneally in an animal model, what is the recommended dose and frequency of administration ?

Previous studies have shown that Defactinib at a dose of 25 mg/kg twice daily or higher statistically significantly inhibited pFAK (Tyr397) at 3 hours, with restoration of expression after 24 hours. Therefore, administration of Defactinib at 25 mg/kg twice daily can be selected as the dosing regimen for subsequent therapeutic experiments.

8/2/2022

tumor growth inhibition

In in PTX-sensitive and PTX-resistant models, we used Defactinib at a dose of 50 mg / kg p.o., which resulted in successful enhancement of tumor growth inhibition by strong paclitaxel.

23/8/2017

immunofluorescence

We used immunofluorescence to detect the two indicators pFAK (Tyr 397)/pYB-1 (Ser 102), and the results showed a significant effect of Defactinib use!

6/2/2020

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Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂