Physicochemical Properties
| Molecular Formula | C27H34CLFN2O4 |
| Molecular Weight | 505.02 |
| Exact Mass | 504.219 |
| CAS # | 1233926-87-8 |
| Related CAS # | PKRA83 hydrochloride hydrate |
| PubChem CID | 66726148 |
| Appearance | Colorless to light yellow ointment |
| LogP | 5 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 35 |
| Complexity | 686 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | CC(C)CN(CC1=CC2=C(C(=C1)Cl)OCCCO2)C(=O)[C@@H]3CCN(C3)CC4=CC(=C(C=C4)F)OC |
| InChi Key | GZHUKRDKTDCKQD-OAQYLSRUSA-N |
| InChi Code | InChI=1S/C27H34ClFN2O4/c1-18(2)14-31(16-20-11-22(28)26-25(13-20)34-9-4-10-35-26)27(32)21-7-8-30(17-21)15-19-5-6-23(29)24(12-19)33-3/h5-6,11-13,18,21H,4,7-10,14-17H2,1-3H3/t21-/m1/s1 |
| Chemical Name | (3R)-N-[(6-chloro-3,4-dihydro-2H-1,5-benzodioxepin-8-yl)methyl]-1-[(4-fluoro-3-methoxyphenyl)methyl]-N-(2-methylpropyl)pyrrolidine-3-carboxamide |
| 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
| ln Vitro | In vitro, microvascular endothelial cells' PK2-induced branching is efficiently inhibited by PKRA83 (1 µg/mL) [1]. The neuroprotective effect of rPK2 in dopaminergic N27 cells is blocked by PKRA83 (2 μM, 24 hours) [3]. RPK2 shields N27 cell channels from MPP+-induced dopaminergic neuronal cell death. |
| ln Vivo | In xenograft tumor models of astroblastoma, PKRA83 (20 mg/kg; i.p.) exhibits anti-activity [1]. 15 mg/kg of PKRA83 administered intraperitoneally once daily for two weeks inhibits |
| Animal Protocol |
Animal/Disease Models: glioblastoma (D456MG glioma cells) nu/nu mouse xenograft tumor model [1] Doses: 20 mg/kg Route of Administration: intraperitoneal (ip) injection, daily Experimental Results: diminished tumor growth rate and tumor weight. The relative blood vessel density diminished and the area of tumor necrosis increased. Animal/Disease Models: collagen-induced arthritis in mice [2] Doses: 15 mg/kg Route of Administration: intraperitoneal (ip) injection, one time/day for 2 weeks Experimental Results: demonstrated less infiltration of inflammatory cells in the joints and thickening of the synovium ( histological evaluation). Reduces IL-1β and 1 L-6 gene expression levels in joints. |
| References |
[1]. A PK2/Bv8/PROK2 antagonist suppresses tumorigenic processes by inhibiting angiogenesis in glioma and blocking myeloid cell infiltration in pancreatic cancer. PLoS One. 2013;8(1):e54916. [2]. Prokineticin 2 antagonist, PKRA7 suppresses arthritis in mice with collagen-induced arthritis. BMC Musculoskelet Disord. 2016 Sep 8;17(1):387. [3]. Prokineticin-2 upregulation during neuronal injury mediates a compensatory protective response against dopaminergic neuronal degeneration. Nat Commun. 2016 Oct 5;7:12932. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~25 mg/mL (~49.50 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. 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 | 1.9801 mL | 9.9006 mL | 19.8012 mL | |
| 5 mM | 0.3960 mL | 1.9801 mL | 3.9602 mL | |
| 10 mM | 0.1980 mL | 0.9901 mL | 1.9801 mL |