WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406262
CAS#: 1061353-68-1
Description: 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.
MedKoo Cat#: 406262
Name: PND-1186
CAS#: 1061353-68-1
Chemical Formula: C25H26F3N5O3
Exact Mass: 501.19877
Molecular Weight: 501.5
Elemental Analysis: C, 59.87; H, 5.23; F, 11.36; N, 13.96; O, 9.57
Synonym: PND1186; PND 1186; PND1186; SR 2516; SR2516; SR2516; VS4718; VS4718; VS 4718.
IUPAC/Chemical Name: 2-((2-((2-methoxy-4-morpholinophenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide.
InChi Key: IGUBBWJDMLCRIK-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: O=C(NC)C1=CC=CC=C1NC2=CC(NC3=C(OC)C=C(N4CCOCC4)C=C3)=NC=C2C(F)(F)F
Appearance: Off-white to grey 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
| Biological target: | PND-1186 (VS-4718) is a potent, highly-specific and reversible inhibitor of FAK with an IC50 of 1.5 nM. |
| In vitro activity: | 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 (Figure 8c). Reference: Cell Death Differ. 2017 May; 24(5): 889–902. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423113/ |
| In vivo activity: | 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. Reference: Pediatr Blood Cancer. 2017 Apr; 64(4): 10.1002/pbc.26304. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578428/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 30.0 | 59.8 | |
| Ethanol | 30.0 | 59.8 |
The following data is based on the product molecular weight 501.5 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. Gnani D, Romito I, Artuso S, Chierici M, De Stefanis C, Panera N, Crudele A, Ceccarelli S, Carcarino E, D'Oria V, Porru M, Giorda E, Ferrari K, Miele L, Villa E, Balsano C, Pasini D, Furlanello C, Locatelli F, Nobili V, Rota R, Leonetti C, Alisi A. Focal adhesion kinase depletion reduces human hepatocellular carcinoma growth by repressing enhancer of zeste homolog 2. Cell Death Differ. 2017 May;24(5):889-902. doi: 10.1038/cdd.2017.34. Epub 2017 Mar 24. PMID: 28338656; PMCID: PMC5423113. 2. Serrels A, Lund T, Serrels B, Byron A, McPherson RC, von Kriegsheim A, Gómez-Cuadrado L, Canel M, Muir M, Ring JE, Maniati E, Sims AH, Pachter JA, Brunton VG, Gilbert N, Anderton SM, Nibbs RJ, Frame MC. Nuclear FAK controls chemokine transcription, Tregs, and evasion of anti-tumor immunity. Cell. 2015 Sep 24;163(1):160-73. doi: 10.1016/j.cell.2015.09.001. PMID: 26406376; PMCID: PMC4597190. 3. Kurmasheva RT, Gorlick R, Kolb EA, Keir ST, Maris JM, Lock RB, Carol H, Kang M, Reynolds CP, Wu J, Houghton PJ, Smith MA. Initial testing of VS-4718, a novel inhibitor of focal adhesion kinase (FAK), against pediatric tumor models by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer. 2017 Apr;64(4):10.1002/pbc.26304. doi: 10.1002/pbc.26304. Epub 2016 Oct 27. PMID: 27786412; PMCID: PMC5578428. 4. Walsh C, Tanjoni I, Uryu S, Tomar A, Nam JO, Luo H, Phillips A, Patel N, Kwok C, McMahon G, Stupack DG, Schlaepfer DD. Oral delivery of PND-1186 FAK inhibitor decreases tumor growth and spontaneous breast to lung metastasis in pre-clinical models. Cancer Biol Ther. 2010 May 15;9(10):778-90. doi: 10.4161/cbt.9.10.11433. PMID: 20234193; PMCID: PMC2933309. |
| In vitro protocol: | 1. Gnani D, Romito I, Artuso S, Chierici M, De Stefanis C, Panera N, Crudele A, Ceccarelli S, Carcarino E, D'Oria V, Porru M, Giorda E, Ferrari K, Miele L, Villa E, Balsano C, Pasini D, Furlanello C, Locatelli F, Nobili V, Rota R, Leonetti C, Alisi A. Focal adhesion kinase depletion reduces human hepatocellular carcinoma growth by repressing enhancer of zeste homolog 2. Cell Death Differ. 2017 May;24(5):889-902. doi: 10.1038/cdd.2017.34. Epub 2017 Mar 24. PMID: 28338656; PMCID: PMC5423113. 2. Serrels A, Lund T, Serrels B, Byron A, McPherson RC, von Kriegsheim A, Gómez-Cuadrado L, Canel M, Muir M, Ring JE, Maniati E, Sims AH, Pachter JA, Brunton VG, Gilbert N, Anderton SM, Nibbs RJ, Frame MC. Nuclear FAK controls chemokine transcription, Tregs, and evasion of anti-tumor immunity. Cell. 2015 Sep 24;163(1):160-73. doi: 10.1016/j.cell.2015.09.001. PMID: 26406376; PMCID: PMC4597190. |
| In vivo protocol: | 1. Kurmasheva RT, Gorlick R, Kolb EA, Keir ST, Maris JM, Lock RB, Carol H, Kang M, Reynolds CP, Wu J, Houghton PJ, Smith MA. Initial testing of VS-4718, a novel inhibitor of focal adhesion kinase (FAK), against pediatric tumor models by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer. 2017 Apr;64(4):10.1002/pbc.26304. doi: 10.1002/pbc.26304. Epub 2016 Oct 27. PMID: 27786412; PMCID: PMC5578428. 2. Walsh C, Tanjoni I, Uryu S, Tomar A, Nam JO, Luo H, Phillips A, Patel N, Kwok C, McMahon G, Stupack DG, Schlaepfer DD. Oral delivery of PND-1186 FAK inhibitor decreases tumor growth and spontaneous breast to lung metastasis in pre-clinical models. Cancer Biol Ther. 2010 May 15;9(10):778-90. doi: 10.4161/cbt.9.10.11433. PMID: 20234193; PMCID: PMC2933309. |
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. doi: 10.1158/1535-7163.MCT-13-1063. Epub 2014 Jun 4. PubMed PMID: 24899686; PubMed Central PMCID: PMC4126870.
