Synonym
ZINC40099027; ZINC 40099027; ZINC-40099027; ZN27; ZN-27; ZN 27;
IUPAC/Chemical Name
2-(4-methoxyphenyl)-N-(2-morpholino-5-(trifluoromethyl)phenyl)pyrrolidine-1-carboxamide
InChi Key
MOEURIVQRFKTCR-UHFFFAOYSA-N
InChi Code
InChI=1S/C23H26F3N3O3/c1-31-18-7-4-16(5-8-18)20-3-2-10-29(20)22(30)27-19-15-17(23(24,25)26)6-9-21(19)28-11-13-32-14-12-28/h4-9,15,20H,2-3,10-14H2,1H3,(H,27,30)
SMILES Code
O=C(N1C(C2=CC=C(OC)C=C2)CCC1)NC3=CC(C(F)(F)F)=CC=C3N4CCOCC4
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
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:
PY-60 is a specific activator of YAP transcriptional activity that targets annexin ANXA2 (Kd = 1.4 µM). PY-60 directly binds to ANXA2 and antagonizes its repression of YAP activity.
In vitro activity:
In human Caco-2 cells, Zn27 stimulated FAK-Tyr-397 phosphorylation independently of key phosphatases that typically inactivate FAK. Zn27 directly activated full-length FAK and its kinase domain. Zn27 increased the maximal activity of FAK and affected its substrate's apparent Km under certain conditions. Zn27's ability to enhance FAK activity through allosteric interaction may be valuable in developing clinical drugs for mucosal wound healing.
Reference: Pharmacol Res Perspect. 2021 Apr;9(2):e00737. https://pubmed.ncbi.nlm.nih.gov/33715263/
In vivo activity:
In two murine small bowel ulcers models, ZINC40099027 dose-dependently activated FAK phosphorylation, without activating Pyk2-Tyr-402 or Src-Tyr-419. ZINC40099027 did not stimulate proliferation, and stimulated wound closure independently of proliferation. ZINC40099027accelerated mucosal wound healing.
Reference: Sci Rep. 2019 Oct 11;9(1):14669. https://pubmed.ncbi.nlm.nih.gov/31604999/
|
Solvent |
mg/mL |
mM |
| Solubility |
| Soluble in DMSO |
0.0 |
100.00 |
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
449.47
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. Oncel S, Basson MD. ZINC40099027 promotes monolayer circular defect closure by a novel pathway involving cytosolic activation of focal adhesion kinase and downstream paxillin and ERK1/2. Cell Tissue Res. 2022 Nov;390(2):261-279. doi: 10.1007/s00441-022-03674-1. Epub 2022 Aug 24. PMID: 36001146.
2. Rashmi, More SK, Wang Q, Vomhof-DeKrey EE, Porter JE, Basson MD. ZINC40099027 activates human focal adhesion kinase by accelerating the enzymatic activity of the FAK kinase domain. Pharmacol Res Perspect. 2021 Apr;9(2):e00737. doi: 10.1002/prp2.737. PMID: 33715263; PMCID: PMC7955952.
3. Oncel S, Gupta R, Wang Q, Basson MD. ZINC40099027 Promotes Gastric Mucosal Repair in Ongoing Aspirin-Associated Gastric Injury by Activating Focal Adhesion Kinase. Cells. 2021 Apr 15;10(4):908. doi: 10.3390/cells10040908. PMID: 33920786; PMCID: PMC8071155.
4. Wang Q, More SK, Vomhof-DeKrey EE, Golovko MY, Basson MD. Small molecule FAK activator promotes human intestinal epithelial monolayer wound closure and mouse ulcer healing. Sci Rep. 2019 Oct 11;9(1):14669. doi: 10.1038/s41598-019-51183-z. PMID: 31604999; PMCID: PMC6789032.
In vitro protocol:
1. Oncel S, Basson MD. ZINC40099027 promotes monolayer circular defect closure by a novel pathway involving cytosolic activation of focal adhesion kinase and downstream paxillin and ERK1/2. Cell Tissue Res. 2022 Nov;390(2):261-279. doi: 10.1007/s00441-022-03674-1. Epub 2022 Aug 24. PMID: 36001146.
2. Rashmi, More SK, Wang Q, Vomhof-DeKrey EE, Porter JE, Basson MD. ZINC40099027 activates human focal adhesion kinase by accelerating the enzymatic activity of the FAK kinase domain. Pharmacol Res Perspect. 2021 Apr;9(2):e00737. doi: 10.1002/prp2.737. PMID: 33715263; PMCID: PMC7955952.
In vivo protocol:
1. Oncel S, Gupta R, Wang Q, Basson MD. ZINC40099027 Promotes Gastric Mucosal Repair in Ongoing Aspirin-Associated Gastric Injury by Activating Focal Adhesion Kinase. Cells. 2021 Apr 15;10(4):908. doi: 10.3390/cells10040908. PMID: 33920786; PMCID: PMC8071155.
2. Wang Q, More SK, Vomhof-DeKrey EE, Golovko MY, Basson MD. Small molecule FAK activator promotes human intestinal epithelial monolayer wound closure and mouse ulcer healing. Sci Rep. 2019 Oct 11;9(1):14669. doi: 10.1038/s41598-019-51183-z. PMID: 31604999; PMCID: PMC6789032.
1: Zan GX, Qin YC, Xie WW, Gao CQ, Yan HC, Wang XQ, Zhou JY. Heat stress disrupts intestinal stem cell migration and differentiation along the crypt- villus axis through FAK signaling. Biochim Biophys Acta Mol Cell Res. 2023 Mar;1870(3):119431. doi: 10.1016/j.bbamcr.2023.119431. Epub 2023 Jan 9. PMID: 36632926.
2: Oncel S, Basson MD. ZINC40099027 promotes monolayer circular defect closure by a novel pathway involving cytosolic activation of focal adhesion kinase and downstream paxillin and ERK1/2. Cell Tissue Res. 2022 Nov;390(2):261-279. doi: 10.1007/s00441-022-03674-1. Epub 2022 Aug 24. PMID: 36001146.
3: Oncel S, Gupta R, Wang Q, Basson MD. ZINC40099027 Promotes Gastric Mucosal Repair in Ongoing Aspirin-Associated Gastric Injury by Activating Focal Adhesion Kinase. Cells. 2021 Apr 15;10(4):908. doi: 10.3390/cells10040908. PMID: 33920786; PMCID: PMC8071155.
4: Wang Q, Gallardo-Macias R, Rashmi, Golovko MY, Elsayed AAR, More SK, Oncel S, Gurvich VJ, Basson MD. Discovery of Novel Small-Molecule FAK Activators Promoting Mucosal Healing. ACS Med Chem Lett. 2021 Feb 16;12(3):356-364. doi: 10.1021/acsmedchemlett.0c00311. PMID: 33738062; PMCID: PMC7957922.
5: Rashmi, More SK, Wang Q, Vomhof-DeKrey EE, Porter JE, Basson MD. ZINC40099027 activates human focal adhesion kinase by accelerating the enzymatic activity of the FAK kinase domain. Pharmacol Res Perspect. 2021 Apr;9(2):e00737. doi: 10.1002/prp2.737. PMID: 33715263; PMCID: PMC7955952.
6: Wang Q, More SK, Vomhof-DeKrey EE, Golovko MY, Basson MD. Small molecule FAK activator promotes human intestinal epithelial monolayer wound closure and mouse ulcer healing. Sci Rep. 2019 Oct 11;9(1):14669. doi: 10.1038/s41598-019-51183-z. PMID: 31604999; PMCID: PMC6789032.
