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MedKoo Cat#: 406262 | Name: PND-1186
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

PND-1186
PND-1186
CAS#1061353-68-1 (free base)

Theoretical Analysis

MedKoo Cat#: 406262

Name: PND-1186

CAS#: 1061353-68-1 (free base)

Chemical Formula: C25H26F3N5O3

Exact Mass: 501.1988

Molecular Weight: 501.50

Elemental Analysis: C, 59.87; H, 5.23; F, 11.36; N, 13.96; O, 9.57

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,350.00 Ready to ship
500mg USD 2,650.00 Ready to ship
1g USD 3,950.00 Ready to ship
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Related CAS #
1061353-68-1 (free base) 1356154-94-3 (HCl)
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
More Info
    Tumor cells can grow in an anchorage-independent manner. This is mediated in part through survival signals that bypass normal growth restraints controlled by integrin cell surface receptors. Focal adhesion kinase (FAK) is a cytoplasmic protein-tyrosine kinase that associates with integrins and modulates various cellular processes including growth, survival, and migration. As increased FAK expression and tyrosine phosphorylation are associated with tumor progression, inhibitors of FAK are being tested for anti-tumor effects    
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 mg/mL mM
Solubility
DMSO 30.0 59.80
Ethanol 30.0 59.80
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 501.50 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.

Recalculate based on batch purity %
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: Jin B, Wang J, Chen Y, Zuo W, Hong B, Li J, Huang F, Zhang M, Wang Y. Focal adhesion kinase induces cardiac remodeling through NF-κB-mediated inflammatory responses in diabetic cardiomyopathy. Int Immunopharmacol. 2023 Jul;120:110280. doi: 10.1016/j.intimp.2023.110280. Epub 2023 May 20. PMID: 37216798. 2: Johnson B, Zhuang L, Rath EM, Yuen ML, Cheng NC, Shi H, Kao S, Reid G, Cheng YY. Exploring MicroRNA and Exosome Involvement in Malignant Pleural Mesothelioma Drug Response. Cancers (Basel). 2022 Sep 30;14(19):4784. doi: 10.3390/cancers14194784. PMID: 36230710; PMCID: PMC9564288. 3: Yuen ML, Zhuang L, Rath EM, Yu T, Johnson B, Sarun KH, Wang Y, Kao S, Linton A, Clarke CJ, McCaughan BC, Takahashi K, Lee K, Cheng YY. The Role of E-Cadherin and microRNA on FAK Inhibitor Response in Malignant Pleural Mesothelioma (MPM). Int J Mol Sci. 2021 Sep 23;22(19):10225. doi: 10.3390/ijms221910225. PMID: 34638565; PMCID: PMC8508233. 4: He J, Zhang S, Qiu Z, Li X, Huang H, Jin W, Xu Y, Shao G, Wang L, Meng J, Wang S, Geng X, Jia Y, Li M, Yang B, Jenny Lu HA, Zhou H. Inhibiting Focal Adhesion Kinase Ameliorates Cyst Development in Polycystin-1-Deficient Polycystic Kidney Disease in Animal Model. J Am Soc Nephrol. 2021 Sep;32(9):2159-2174. doi: 10.1681/ASN.2020111560. PMID: 34465607; PMCID: PMC8729842. 5: Mohamed AA, Thomsen A, Follo M, Zamboglou C, Bronsert P, Mostafa H, Amen A, Mekawy M, Grosu AL, Brunner TB. FAK inhibition radiosensitizes pancreatic ductal adenocarcinoma cells in vitro. Strahlenther Onkol. 2021 Jan;197(1):27-38. doi: 10.1007/s00066-020-01666-0. Epub 2020 Jul 23. PMID: 32705304; PMCID: PMC7801360. 6: Jiang H, Liu X, Knolhoff BL, Hegde S, Lee KB, Jiang H, Fields RC, Pachter JA, Lim KH, DeNardo DG. Development of resistance to FAK inhibition in pancreatic cancer is linked to stromal depletion. Gut. 2020 Jan;69(1):122-132. doi: 10.1136/gutjnl-2018-317424. Epub 2019 May 10. PMID: 31076405; PMCID: PMC7167297. 7: Wang S, Hwang EE, Guha R, O'Neill AF, Melong N, Veinotte CJ, Conway Saur A, Wuerthele K, Shen M, McKnight C, Alexe G, Lemieux ME, Wang A, Hughes E, Xu X, Boxer MB, Hall MD, Kung A, Berman JN, Davis MI, Stegmaier K, Crompton BD. High- throughput Chemical Screening Identifies Focal Adhesion Kinase and Aurora Kinase B Inhibition as a Synergistic Treatment Combination in Ewing Sarcoma. Clin Cancer Res. 2019 Jul 15;25(14):4552-4566. doi: 10.1158/1078-0432.CCR-17-0375. Epub 2019 Apr 12. PMID: 30979745; PMCID: PMC6634997. 8: Muz B, Buggio M, Azab F, de la Puente P, Fiala M, Padval MV, Weaver DT, Pachter JA, Vij R, Azab AK. PYK2/FAK inhibitors reverse hypoxia-induced drug resistance in multiple myeloma. Haematologica. 2019 Jul;104(7):e310-e313. doi: 10.3324/haematol.2018.194688. Epub 2019 Jan 17. PMID: 30655367; PMCID: PMC6601110. 9: 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. 10: 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. 11: Jiang H, Hegde S, Knolhoff BL, Zhu Y, Herndon JM, Meyer MA, Nywening TM, Hawkins WG, Shapiro IM, Weaver DT, Pachter JA, Wang-Gillam A, DeNardo DG. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat Med. 2016 Aug;22(8):851-60. doi: 10.1038/nm.4123. Epub 2016 Jul 4. PMID: 27376576; PMCID: PMC4935930. 12: 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. 13: Zhang Y, Moschetta M, Huynh D, Tai YT, Zhang Y, Zhang W, Mishima Y, Ring JE, Tam WF, Xu Q, Maiso P, Reagan M, Sahin I, Sacco A, Manier S, Aljawai Y, Glavey S, Munshi NC, Anderson KC, Pachter J, Roccaro AM, Ghobrial IM. Pyk2 promotes tumor progression in multiple myeloma. Blood. 2014 Oct 23;124(17):2675-86. doi: 10.1182/blood-2014-03-563981. Epub 2014 Sep 12. PMID: 25217697; PMCID: PMC4208283. 14: FAK inhibitor kills mesothelioma cells. Cancer Discov. 2014 Aug;4(8):OF3. doi: 10.1158/2159-8290.CD-NB2014-093. Epub 2014 Jun 19. PMID: 25092758. 15: 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. PMID: 24899686; PMCID: PMC4126870. 16: Schaller MD, Frisch SM. PND-1186 FAK inhibitor selectively promotes tumor cell apoptosis in three-dimensional environments. Cancer Biol Ther. 2010 May 15;9(10):791-3. doi: 10.4161/cbt.11729. Epub 2010 May 8. PMID: 20364110. 17: 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. 18: Tanjoni I, Walsh C, Uryu S, Tomar A, Nam JO, Mielgo A, Lim ST, Liang C, Koenig M, Sun C, Patel N, Kwok C, McMahon G, Stupack DG, Schlaepfer DD. PND-1186 FAK inhibitor selectively promotes tumor cell apoptosis in three-dimensional environments. Cancer Biol Ther. 2010 May 15;9(10):764-77. doi: 10.4161/cbt.9.10.11434. PMID: 20234191; PMCID: PMC2933317.