PND-1186

PND-1186, also known as SR-2156 and VS-4718, is a potent FAK inhibitor with a 50% inhibitory concentration (IC50) of 1.5 nM in vitro. PND-1186 has an IC50 of ~100 nM in breast carcinoma cells. Notably, 1.0 µM PND-1186 (>5-fold above IC50) had limited effects on cell proliferation. However, under non-adherent conditions as spheroids and as colonies in soft agar, 0.1 µM PND-1186 blocked FAK and p130Cas tyrosine phosphorylation, promoted caspase-3 activation, and triggered cell apoptosis. PND-1186 inhibited 4T1 breast carcinoma subcutaneous tumor growth correlated with elevated tumor cell apoptosis and caspase 3 activation.

Product information

CAS Number: 1061353-68-1

Molecular Weight: 501.50

Formula: C25H26F3N5O3

Synonym:

SR-2516

PND 1186

PND1186

SR 2516

SR2516

Chemical Name: 2-[(2-{[2-methoxy-4-(morpholin-4-yl)phenyl]amino}-5-(trifluoromethyl)pyridin-4-yl)amino]-N-methylbenzamide

Smiles: COC1=CC(=CC=C1NC1=CC(NC2=CC=CC=C2C(=O)NC)=C(C=N1)C(F)(F)F)N1CCOCC1

InChiKey: IGUBBWJDMLCRIK-UHFFFAOYSA-N

InChi: InChI=1S/C25H26F3N5O3/c1-29-24(34)17-5-3-4-6-19(17)31-21-14-23(30-15-18(21)25(26,27)28)32-20-8-7-16(13-22(20)35-2)33-9-11-36-12-10-33/h3-8,13-15H,9-12H2,1-2H3,(H,29,34)(H2,30,31,32)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

HCC cells were exposed to 0.5 μM and 1 μM of PND-1186. The treatment with PND-1186 decreased cell proliferation rate (Supplementary Figure S8a) by significantly inducing G0/G1 phase arrest and apoptosis at 48 h (Supplementary Figure S8b, Figure 8a). Accordingly, PND-1186 treatment caused downregulation of FAK Tyr-397 phosphorylation and cyclin D1 amount (Supplementary Figures S8c and d) and increased the expression of both p21 and cleaved caspase-3 at 48 h (Figure 8b). As expected, 1 μM PND-1186 significantly downregulated EZH2 mRNA and upregulated NOTCH2 expression.

In Vivo:

VS-4718 induced significant differences in EFS distribution compared to control in 18 of 36 (50%) of the evaluable solid tumor mice xenografts and in 0 of 8 (0%) of the evaluable ALL xenografts, including the Ph+ ALL xenograft, ALL-4 (Table 2). Significant differences in EFS distribution were most commonly observed for the osteosarcoma panel (6 of 6), the rhabdomyosarcoma panel (4 of 6), and the neuroblastoma panel (4 of 6). VS-4718 did not induce tumor growth inhibition meeting criteria for intermediate EFS T/C(>2) activity in either the solid tumor or ALL xenografts. Only 3 models met criteria for PD2 responses (one Ewing, rhabdomyosarcoma, and neuroblastoma xenograft each). Objective responses were not observed for the solid tumor or ALL xenografts.

References:

1. Tancioni I, Uryu S, Sulzmaier FJ, Shah NR, Lawson C, Miller NL, Jean C, Chen XL, Ward KK, Schlaepfer DD. FAK Inhibition disrupts a β5 integrin signaling axis controlling anchorage-independent ovarian carcinoma growth. Mol Cancer Ther. 2014 Aug;13(8):2050-61.

Products are for research use only. Not for human use.