ZINC40099027, also known as ZN27, is a specific focal adhesion kinase (FAK) activator that promotes mucosal wound closure in mice after ischemic or NSAID-induced injury. ZINC40099027 activates cellular FAK and promotes intestinal epithelial wound closure in vitro and in mice. ZN27 ameliorates sustained aspirin-related gastric mucosal injury through a pathway involving FAK activation. ZN27-analogues may help promote gastric mucosal repair.

Physicochemical Properties

Molecular Formula	C23H26F3N3O3
Molecular Weight	449.466056346893
Exact Mass	449.19
Elemental Analysis	C, 61.46; H, 5.83; F, 12.68; N, 9.35; O, 10.68
CAS #	1211825-25-0
PubChem CID	45889460
Appearance	White to off-white solid powder
LogP	3.7
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	4
Heavy Atom Count	32
Complexity	621
Defined Atom Stereocenter Count	0
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)
Chemical Name	2-(4-methoxyphenyl)-N-(2-morpholino-5-(trifluoromethyl)phenyl)pyrrolidine-1-carboxamide
Synonyms	ZINC40099027; ZINC 40099027; ZINC-40099027; ZN27; ZN-27; ZN 27;
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

References

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.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~222.48 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (5.56 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.56 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2248 mL	11.1242 mL	22.2484 mL
	5 mM	0.4450 mL	2.2248 mL	4.4497 mL
	10 mM	0.2225 mL	1.1124 mL	2.2248 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.