| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
PKRA-83 potently targets prokineticin receptors PKR1 and PKR2, antagonizing the binding of prokineticin 2 (PK2). It shows high affinity for both receptors, with IC50 values of 5.0 nM for PKR1 and 8.2 nM for PKR2. It can also penetrate the blood-brain barrier.
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| 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.
PKRA-83 effectively antagonizes PK2 receptors. At 1 ug/mL, it reduces PK2-induced microvascular endothelial cell branching. At 2 uM (24 h), it blocks the neuroprotective action of recombinant PK2 in dopaminergic N27 cells. It exhibits anticancer, anti-angiogenic, and anti-arthritis activities in vitro and in vivo. |
| 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
PKRA-83 demonstrates robust in vivo activity. At 20 mg/kg (IP), it shows anti-tumor activity in glioblastoma xenograft models. At 15 mg/kg (IP, daily for 2 weeks), it inhibits arthritis in a mouse model of collagen-induced arthritis. It can also effectively reduce PK2-induced microvascular branching in vivo. |
| Enzyme Assay |
The antagonist activity of PKRA-83 is measured using a competitive binding assay. Radiolabeled PK2 is incubated with recombinant PKR1 or PKR2 in the presence of varying concentrations of PKRA-83. The amount of bound label is measured after washing. The IC50 values (5.0 nM and 8.2 nM) are calculated from the competition curves.
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| Cell Assay |
Human microvascular endothelial cells (HMVECs) are cultured and treated with PK2 in the presence or absence of PKRA-83 (1 ug/mL). Endothelial cell branching and tube formation are assessed under a microscope. For neuroprotection studies, dopaminergic N27 cells are pre-treated with PKRA-83 (2 uM, 24 h) followed by MPP+ and rPK2. Cell viability is assessed by MTT assay.
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| 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. For anti-tumor studies, glioblastoma cells are implanted subcutaneously into immunodeficient mice. PKRA-83 (20 mg/kg) is administered by intraperitoneal injection. Tumor volumes are measured regularly. For anti-arthritis studies, collagen-induced arthritis is induced in mice. PKRA-83 (15 mg/kg, IP, daily for 14 days) is administered, and clinical arthritis scores are assessed. |
| ADME/Pharmacokinetics |
Detailed PK parameters for PKRA-83 are not extensively documented. The compound has a molecular weight of 505.02 g/mol and is soluble in DMSO (25 mg/mL). It can penetrate the blood-brain barrier, which is relevant for neuroprotection studies. Comprehensive ADME data are not publicly reported.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for PKRA-83 are not extensively documented. As a research compound, comprehensive acute and sub-chronic toxicity studies have not been publicly reported. In animal efficacy studies, the compound appears well tolerated at the doses used (15-20 mg/kg IP).
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| References |
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| Additional Infomation |
PKRA-83 is a specific PK2 receptor antagonist that serves as a chemical probe to study the prokineticin signaling pathway. It has potential therapeutic applications in cancer (anti-angiogenesis, anti-tumor), inflammatory diseases (arthritis), and neuroprotection. The compound is not an approved clinical drug. It is identified as PKRA83 or PKRA7 in the scientific literature.
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| Molecular Formula |
C27H34CLFN2O4
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|---|---|
| Molecular Weight |
505.02
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| Exact Mass |
504.219
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| CAS # |
1233926-87-8
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| Related CAS # |
PKRA83 hydrochloride hydrate
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| PubChem CID |
66726148
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| Appearance |
Colorless to light yellow ointment
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| LogP |
5
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
35
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| Complexity |
686
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC(C)CN(CC1=CC2=C(C(=C1)Cl)OCCCO2)C(=O)[C@@H]3CCN(C3)CC4=CC(=C(C=C4)F)OC
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| InChi Key |
GZHUKRDKTDCKQD-OAQYLSRUSA-N
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| 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
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| 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
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~49.50 mM)
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| 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 |
*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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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